WorldWideScience

Sample records for test protocol jp-p-1-1

  1. Isolation and characterization of the pesticide-degrading plasmid pJP1 from Alcaligenes paradoxus

    International Nuclear Information System (INIS)

    Fisher, P.R.; Appleton, J.; Pemberton, J.M.

    1978-01-01

    A strain of Alcaligenes paradoxus, unable to degrade phenoxyacetic acid, was shown to degrade two synthetic derivatives of this molecule, the herbicides 2,4-dichlorophenoxyacetic acid and 2-methyl-4-chlorophenoxyacetic acid. The ability to degrade these pesticides is encoded by a 58-megadalton conjugal plasmid, pJP1

  2. LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer.

    Science.gov (United States)

    Zhang, Gang; Li, Shuwei; Lu, Jiafei; Ge, Yuqiu; Wang, Qiaoyan; Ma, Gaoxiang; Zhao, Qinghong; Wu, Dongdong; Gong, Weida; Du, Mulong; Chu, Haiyan; Wang, Meilin; Zhang, Aihua; Zhang, Zhengdong

    2018-05-02

    Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.

  3. 77 FR 59184 - J.P. Morgan Ventures Energy Corporation; Notice of Initiation of Proceeding and Refund Effective...

    Science.gov (United States)

    2012-09-26

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-103-000] J.P. Morgan... statements by J.P. Morgan Ventures Energy Corporation constitute violations of section 35.41(b) of the Commission's regulations under the Federal Power Act (FPA).\\1\\ J.P. Morgan Ventures Energy Corporation, 140...

  4. Quench detection electronics testing protocol for SST-1 magnets

    International Nuclear Information System (INIS)

    Banaudha, Moni; Varmora, Pankaj; Parghi, Bhadresh; Prasad, Upendra

    2017-01-01

    Quench Detection (QD) system consisting 204 signal channels has been successfully installed and working well during plasma experiment of SST-1 Tokamak. QD system requires testing, validation and maintenance in every SST-1 campaign for better reliability and maintainability of the system. Standalone test of each channel of the system is essential for hard-ware validation. The standard Testing Protocol follow in every campaign which validate each section of QD electronics as well as voltage tap signal cables which are routed inside the cryostat and then extended outside of the SST-1 machine up-to the magnet control room. Fiber link for Quench signal transmission to the SST-1 magnet power supply is also test and validate before every plasma campaign. Precise instrument used as a dummy source of quench signal and for manual quench generation to test the each channel and Master Quench Logic. Each signal Integrated with the magnet DAQ system, signal observed at 1Hz and 50Hz configuration to validate the logging data, compare with actual and previous test data. This paper describes the testing protocol follow in every campaign to validate functionality of QD electronics, limitation of testing, test results and overall integration of the quench detection system for SST-1 magnet. (author)

  5. CATS Deliverable 5.1 : CATS verification of test matrix and protocol

    OpenAIRE

    Uittenbogaard, J.; Camp, O.M.G.C. op den; Montfort, S. van

    2016-01-01

    This report summarizes the work conducted within work package (WP) 5 "Verification of test matrix and protocol" of the Cyclist AEB testing system (CATS) project. It describes the verification process of the draft CATS test matrix resulting from WP1 and WP2, and the feasibility of meeting requirements set by CATS consortium based on requirements in Euro NCAP AEB protocols regarding accuracy, repeatability and reproducibility using the developed test hardware. For the cases where verification t...

  6. CATS Deliverable 5.1 : CATS verification of test matrix and protocol

    NARCIS (Netherlands)

    Uittenbogaard, J.; Camp, O.M.G.C. op den; Montfort, S. van

    2016-01-01

    This report summarizes the work conducted within work package (WP) 5 "Verification of test matrix and protocol" of the Cyclist AEB testing system (CATS) project. It describes the verification process of the draft CATS test matrix resulting from WP1 and WP2, and the feasibility of meeting

  7. Chinese Commission of Science Technology and Industry for National Defense Senior Vice Minister CHEN Qiufa visiting ALICE experiment on 1st November 2007 with CERN Director-General R. Aymar and Adviser J.-P. Revol. Thursday, 1st and Friday, 2nd November 2007

    CERN Multimedia

    Maximilien Brice

    2007-01-01

    Chinese Commission of Science Technology and Industry for National Defense Senior Vice Minister CHEN Qiufa visiting ALICE experiment on 1st November 2007 with CERN Director-General R. Aymar and Adviser J.-P. Revol. Thursday, 1st and Friday, 2nd November 2007

  8. 76 FR 41829 - J.P. Morgan Securities LLC, et al.; Notice of Application and Temporary Order

    Science.gov (United States)

    2011-07-15

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-29719; 812-13919] J.P. Morgan Securities LLC... entered against J.P. Morgan Securities LLC (``JPMS'') on July 8, 2011 by the United States District Court... Distribution Services, Inc. (``JPMDS''), J.P. Morgan Institutional Investments, Inc. (``JPMII''), J.P. Morgan...

  9. 76 FR 39447 - J.P. Morgan Securities LLC, et al.; Notice of Application and Temporary Order

    Science.gov (United States)

    2011-07-06

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-29711; File No. 812-13914] J.P. Morgan... injunction entered against J.P. Morgan Securities LLC (``J.P. Morgan Securities'') on June 29, 2011 by the... order. Applicants: J.P. Morgan Securities; Bear Stearns Asset Management Inc. (``BSAM''); Bear Stearns...

  10. 78 FR 3042 - J.P. Morgan Securities LLC, et al.; Notice of Application and Temporary Order

    Science.gov (United States)

    2013-01-15

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-30347; 812-14094] J.P. Morgan Securities LLC... entered against J.P. Morgan Securities LLC (``JPMS''), EMC Mortgage, LLC (``EMC''), Bear Stearns Asset... Inc. (``SACO'') and J.P. Morgan Acceptance Corporation I (``JPMAC'') (together, the ``Defendants'') on...

  11. Quantitative discrimination of Aggregatibacter actinomycetemcomitans highly leukotoxic JP2 clone from non-JP2 clones in diagnosis of aggressive periodontitis.

    Science.gov (United States)

    Yoshida, Akihiro; Ennibi, Oum-Keltoum; Miyazaki, Hideo; Hoshino, Tomonori; Hayashida, Hideaki; Nishihara, Tatsuji; Awano, Shuji; Ansai, Toshihiro

    2012-10-11

    Aggregatibacter actinomycetemcomitans is the etiological agent of periodontitis, and there is a strong association between clone JP2 and aggressive periodontitis in adolescents of African descent. The JP2 clone has an approximately 530-bp deletion (∆530) in the promoter region of the lkt/ltx gene, which encodes leukotoxin, and this clone has high leukotoxic activity. Therefore, this clone is very important in aggressive periodontitis. To diagnose this disease, culture methods and conventional PCR techniques are used. However, quantitative detection based on qPCR for the JP2 clone has not been developed due to genetic difficulties. In this study, we developed a qPCR-based quantification method specific to the JP2 clone. Based on our analysis of the DNA sequence of the lkt/ltx gene and its flanking region, we designed a reverse primer specific for the ∆530 deletion border sequence and developed a JP2-specific PCR-based quantification method using this primer. We also analyzed the DNA sequence of the ∆530 locus and found it to be highly conserved (97-100%) among 17 non-JP2 strains. Using the ∆530 locus, we designed a qPCR primer-probe set specific to non-JP2 clones. Next, we determined the numbers of JP2 and non-JP2 clone cells in the periodontal pockets of patients with aggressive periodontitis. The JP2-specific primers specifically amplified the genomic DNA of the A. actinomycetemcomitans JP2 clone and did not react with other bacterial DNA, whereas the non-JP2 specific primers reacted only with A. actinomycetemcomitans non-JP2 clones. Samples from the 88 periodontal sites in the 11 patients with aggressive periodontitis were analyzed. The bacterial cell numbers in 88 periodontal sites ranged from 0 to 4.8 × 10(8) (mean 1.28 × 10(7)) for JP2 clones and from 0 to 1.6 × 10(6) for non-JP2 clones (mean 1.84 × 10(5)). There were significant differences in the JP2 cell number between a clinical attachment level (CAL) ≤6 mm and a level ≥7 mm (p clones. This

  12. File list: InP.Pan.50.AllAg.PANC-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.50.AllAg.PANC-1 hg19 Input control Pancreas PANC-1 SRX190309,SRX150696,SRX1...99860,SRX101486,SRX190029,SRX190252,SRX644404 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Pan.50.AllAg.PANC-1.bed ...

  13. File list: InP.Pan.20.AllAg.PANC-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.20.AllAg.PANC-1 hg19 Input control Pancreas PANC-1 SRX101486,SRX190309,SRX1...50696,SRX190252,SRX644404,SRX199860,SRX190029 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Pan.20.AllAg.PANC-1.bed ...

  14. File list: InP.Pan.05.AllAg.PANC-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.05.AllAg.PANC-1 hg19 Input control Pancreas PANC-1 SRX190309,SRX101486,SRX1...50696,SRX190252,SRX644404,SRX190029,SRX199860 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Pan.05.AllAg.PANC-1.bed ...

  15. File list: InP.Pan.10.AllAg.PANC-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.10.AllAg.PANC-1 hg19 Input control Pancreas PANC-1 SRX190309,SRX101486,SRX1...50696,SRX190252,SRX644404,SRX199860,SRX190029 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Pan.10.AllAg.PANC-1.bed ...

  16. Quantitative discrimination of Aggregatibacter actinomycetemcomitans highly leukotoxic JP2 clone from non-JP2 clones in diagnosis of aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Yoshida Akihiro

    2012-10-01

    Full Text Available Abstract Background Aggregatibacter actinomycetemcomitans is the etiological agent of periodontitis, and there is a strong association between clone JP2 and aggressive periodontitis in adolescents of African descent. The JP2 clone has an approximately 530-bp deletion (∆530 in the promoter region of the lkt/ltx gene, which encodes leukotoxin, and this clone has high leukotoxic activity. Therefore, this clone is very important in aggressive periodontitis. To diagnose this disease, culture methods and conventional PCR techniques are used. However, quantitative detection based on qPCR for the JP2 clone has not been developed due to genetic difficulties. In this study, we developed a qPCR-based quantification method specific to the JP2 clone. Methods Based on our analysis of the DNA sequence of the lkt/ltx gene and its flanking region, we designed a reverse primer specific for the ∆530 deletion border sequence and developed a JP2-specific PCR-based quantification method using this primer. We also analyzed the DNA sequence of the ∆530 locus and found it to be highly conserved (97–100% among 17 non-JP2 strains. Using the ∆530 locus, we designed a qPCR primer–probe set specific to non-JP2 clones. Next, we determined the numbers of JP2 and non-JP2 clone cells in the periodontal pockets of patients with aggressive periodontitis. Results The JP2-specific primers specifically amplified the genomic DNA of the A. actinomycetemcomitans JP2 clone and did not react with other bacterial DNA, whereas the non-JP2 specific primers reacted only with A. actinomycetemcomitans non-JP2 clones. Samples from the 88 periodontal sites in the 11 patients with aggressive periodontitis were analyzed. The bacterial cell numbers in 88 periodontal sites ranged from 0 to 4.8 × 108 (mean 1.28 × 107 for JP2 clones and from 0 to 1.6 × 106 for non-JP2 clones (mean 1.84 × 105. There were significant differences in the JP2 cell number between a clinical attachment level

  17. TRAC-P validation test matrix. Revision 1.0

    International Nuclear Information System (INIS)

    Hughes, E.D.; Boyack, B.E.

    1997-01-01

    This document briefly describes the elements of the Nuclear Regulatory Commission's (NRC's) software quality assurance program leading to software (code) qualification and identifies a test matrix for qualifying Transient Reactor Analysis Code (TRAC)-Pressurized Water Reactor Version (-P), or TRAC-P, to the NRC's software quality assurance requirements. Code qualification is the outcome of several software life-cycle activities, specifically, (1) Requirements Definition, (2) Design, (3) Implementation, and (4) Qualification Testing. The major objective of this document is to define the TRAC-P Qualification Testing effort

  18. Analysis list: Srebf1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Srebf1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Sreb...f1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Srebf1.5.tsv http://dbarchive.biosciencedbc.j...p/kyushu-u/mm9/target/Srebf1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Srebf1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Srebf1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  19. TRAC-P validation test matrix. Revision 1.0

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, E.D.; Boyack, B.E.

    1997-09-05

    This document briefly describes the elements of the Nuclear Regulatory Commission`s (NRC`s) software quality assurance program leading to software (code) qualification and identifies a test matrix for qualifying Transient Reactor Analysis Code (TRAC)-Pressurized Water Reactor Version (-P), or TRAC-P, to the NRC`s software quality assurance requirements. Code qualification is the outcome of several software life-cycle activities, specifically, (1) Requirements Definition, (2) Design, (3) Implementation, and (4) Qualification Testing. The major objective of this document is to define the TRAC-P Qualification Testing effort.

  20. Comparative performance of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1 for obtaining platelet rich plasma.

    Directory of Open Access Journals (Sweden)

    Augusto Aguirre

    2017-01-01

    Full Text Available Objective: To compare the platelet concentration obtained after application of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1 and the protocol of Anitua and Andia (PRP-A for obtaining platelet rich plasma. Material and Method: A descriptive, cross-sectional and comparative study was carried out with a simple random probabilistic sample consisting of 16 patients who attended the Periodontics service of the Unit of Second Specialization in Stomatology of the National University of Trujillo. Five blood samples were obtained from each patient, after applying a health questionnaire to rule out any disease or drug consumption, in order to obtain the baseline platelet concentration and that obtained after PRGF-U1 and PRP-A. To compare the platelet concentrations of the two protocols, Student’s t-test was used considering a significance level of p<0.05. RESULTS: The baseline platelet concentration was 371,250±68,203 platelets/μL, for PRGF-U1 it was 747,875±121,645 platelets/μL and for PRP-A it was 595,000±129,202 platelets/μL. A statistically significant difference (p<0.001 was found between both protocols. Conclusion: The PRGF-U1 protocol yielded a higher platelet concentration compared to the Anitúa and Andía protocol.

  1. Nondestructive testing methods in building industry '83. Part 1

    International Nuclear Information System (INIS)

    1983-10-01

    The conference heard 52 papers of which 11 were incorporated in INIS. The subject of these was the use of radiometric methods and instruments for nondestructive testing of building materials and ways of testing the quality of concrete during nuclear power plant construction. (J.P.)

  2. Analysis list: Ptf1a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Ptf1a Embryo,Pancreas + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/P...tf1a.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ptf1a.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/target/Ptf1a.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ptf1a.Embryo.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Ptf1a.Pancreas.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pancreas.gml ...

  3. 78 FR 24192 - J.P. Morgan Ventures Energy Corp. v. Midwest Independent System Operator, Inc. PJM...

    Science.gov (United States)

    2013-04-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL13-58-000] J.P. Morgan Ventures Energy Corp. v. Midwest Independent System Operator, Inc. PJM Interconnection, L.L.C.; Notice of Complaint Take notice that on April 10, 2013, J.P. Morgan Ventures Energy Corporation (JPMVEC or Complainant...

  4. 1.8. Brand*, HA Badenhorst, FK 8iebrits and EH Kemm JP Hayes et ...

    African Journals Online (AJOL)

    Brand*, H.A. Badenhorst, F.K. 8iebrits and E.H. Kemm. Animal and Dairy Science Research Institute, Private Bag X2, Irene 1675, Republic of South Africa. J.P. Hayes. Department of Poultry Science, University of Stellenbosch, Stellenbosch 7600, Republic of South Africa. The experiment was conducted to compare the ...

  5. 78 FR 16262 - J.P. Morgan Ventures Energy Corporation; Supplemental Notice That Initial Market-Based Rate...

    Science.gov (United States)

    2013-03-14

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER13-830-000] J.P. Morgan... Blanket Section 204 Authorization This is a supplemental notice in the above-referenced proceeding, of J.P...-8659. Dated: March 7, 2013. Nathaniel J. Davis, Sr., Deputy Secretary. [FR Doc. 2013-05859 Filed 3-13...

  6. Continuous wave protocol for simultaneous polarization and optical detection of P1-center electron spin resonance

    Science.gov (United States)

    Kamp, E. J.; Carvajal, B.; Samarth, N.

    2018-01-01

    The ready optical detection and manipulation of bright nitrogen vacancy center spins in diamond plays a key role in contemporary quantum information science and quantum metrology. Other optically dark defects such as substitutional nitrogen atoms (`P1 centers') could also become potentially useful in this context if they could be as easily optically detected and manipulated. We develop a relatively straightforward continuous wave protocol that takes advantage of the dipolar coupling between nitrogen vacancy and P1 centers in type 1b diamond to detect and polarize the dark P1 spins. By combining mutual spin flip transitions with radio frequency driving, we demonstrate the simultaneous optical polarization and detection of the electron spin resonance of the P1 center. This technique should be applicable to detecting and manipulating a broad range of dark spin populations that couple to the nitrogen vacancy center via dipolar fields, allowing for quantum metrology using these spin populations.

  7. LMFBR transducer performance in SLSF tests P1 and P2

    International Nuclear Information System (INIS)

    English, J.J.; Anderson, T.T.; Kuzay, T.M.; Wilson, R.E.; Pedersen, D.R.; Kaiser, W.C.; Klingler, W.B.

    1977-01-01

    The reliability and problem areas of sodium-immersed thermocouples, pressure transducers and flowmeters are presented for experiments P1 and P2 of the Sodium Loop Safety Facility (SLSF). The SLSF is a doubly-contained sodium loop situated in a core position of the Engineering Test Reactor at the Idaho National Engineering Laboratory

  8. Final Joint Test Protocol JP-P-1-1 for Validation of Alternatives to Lead-Containing Dry Film Lubricants for Antigalling/Antifretting, Antiseizing, and Assembly Aid Applications

    National Research Council Canada - National Science Library

    Thomstatter, John

    2004-01-01

    ... an additional test requirement for humidity resistance. This requirement was identified by turbine engine original equipment manufacturers based on experience in evaluating water-based dry film lubricants (DFLs...

  9. BDML Metadata: 1 [SSBD[Archive

    Lifescience Database Archive (English)

    Full Text Available BY-NC-SA 0.180 df2a9568-9c33-4b48-b138-46548bccff6d 0.105 x 0.105 x 0.5 (micrometer), 40 (second) http://ssbd.qbic.riken.jp/data.../source/Ce_KK_P002/RNAi_B0336.10_040518_01.zip http://ssbd.qbic.riken.jp/data.../bdml/Ce_KK_P002/RNAi_B0336.10_040518_01.bdml0.18.xml http://ssbd.qbic.riken.jp/data/pdpml/...Ce_KK_P002.pdpml0.06.xml http://ssbd.qbic.riken.jp/search/df2a9568-9c33-4b48-b138-46548bccff6d/ http://ssbd.qbic.riken.jp/omero/webclient/?show=dataset-1 ...

  10. Symbolism in J.P. Clark's The Ozidi Saga | Osuagwu | Lwati: A ...

    African Journals Online (AJOL)

    Symbolism in J.P. Clark's The Ozidi Saga. N Osuagwu, E Onyekachi. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

  11. Expedient Protocols for the Installation of Pyrimidine Based Privileged Templates on 2-Position of Pyrrolo[2,1-c][1,4]-benzodiazepine Nucleus Linked Through a p-phenoxyl Spacer

    Directory of Open Access Journals (Sweden)

    Anshu Agarwal

    2012-01-01

    Full Text Available Exceedingly facile single step expedient protocols based on the versatility and reactivity of corresponding intermediates : [2-(dimethylaminomethylene ketone] (5 and chalcone (6, derived from 2-(p-acetyl phenoxyl substituted analogue of pyrrolo[2,1-c][1,4]-benzodiazepine (4, have been developed to provide an easy installation of the pyrimidine based privileged templates at 2-position of pyrrolo[2,1-c][1,4]-benzodiazepine through a p-phenoxyl spacer, by utilizing the synthetic strategy depicted in schemes-1 and 2.

  12. Comparisons of TRAC-PF-1 calculations with semiscale Mod-3 small-break tests S-SB-P1 and S-SB-P7

    International Nuclear Information System (INIS)

    Sahota, M.S.

    1982-01-01

    Semiscale Tests S-SB-P1 and S-SB-P7 conducted in the Semiscale Mod-3 facility at the Idaho National Engineering Laboratory are analyzed using the latest released version of the Transient Reactor Analysis Code (TRAC-PF1). The results are used to assess TRAC-PF1 predictions of thermal-hydraulic phenomena and the effects of break size and pump operation on system response during slow transients. Tests S-SB-P1 and S-SB-P7 simulated an equivalent pressurized-water-reactor (PWR) 2.5% communicative cold-leg break for early and late pump trips, respectively, with only high-pressure injection (HPI) into the cold legs. The parameters examined include break flow, primary-system pressure response, primary-system mass distribution, and core characteristics

  13. Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol.

    Science.gov (United States)

    Wang, Y T; Mohammed, S D; Farmer, A D; Wang, D; Zarate, N; Hobson, A R; Hellström, P M; Semler, J R; Kuo, B; Rao, S S; Hasler, W L; Camilleri, M; Scott, S M

    2015-09-01

    The wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. To investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. Regional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. For GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17 min, P = 0.0307), and also longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P = 0.0077). Increasing age was associated with shorter small bowel transit time (P = 0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24 h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. Regional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research. © 2015 John Wiley & Sons Ltd.

  14. CPM Test-Retest Reliability: "Standard" vs "Single Test-Stimulus" Protocols.

    Science.gov (United States)

    Granovsky, Yelena; Miller-Barmak, Adi; Goldstein, Oren; Sprecher, Elliot; Yarnitsky, David

    2016-03-01

    Assessment of pain inhibitory mechanisms using conditioned pain modulation (CPM) is relevant clinically in prediction of pain and analgesic efficacy. Our objective is to provide necessary estimates of intersession CPM reliability, to enable transformation of the CPM paradigm into a clinical tool. Two cohorts of young healthy subjects (N = 65) participated in two dual-session studies. In Study I, a Bath-Thermode CPM protocol was used, with hot water immersion and contact heat as conditioning- and test-stimuli, respectively, in a classical parallel CPM design introducing test-stimulus first, and then the conditioning- and repeated test-stimuli in parallel. Study II consisted of two CPM protocols: 1) Two-Thermodes, one for each of the stimuli, in the same parallel design as above, and 2) single test-stimulus (STS) protocol with a single administration of a contact heat test-stimulus, partially overlapped in time by a remote shorter contact heat as conditioning stimulus. Test-retest reliability was assessed within 3-7 days. The STS-CPM had superior reliability intraclass correlation (ICC 2 ,: 1  = 0.59) over Bath-Thermode (ICC 2 ,: 1  = 0.34) or Two-Thermodes (ICC 2 ,: 1  = 0.21) protocols. The hand immersion conditioning pain had higher reliability than thermode pain (ICC 2 ,: 1  = 0.76 vs ICC 2 ,: 1  = 0.16). Conditioned test-stimulus pain scores were of good (ICC 2 ,: 1  = 0.62) or fair (ICC 2 ,: 1  = 0.43) reliability for the Bath-Thermode and the STS, respectively, but not for the Two-Thermodes protocol (ICC 2 ,: 1  = 0.20). The newly developed STS-CPM paradigm was more reliable than other CPM protocols tested here, and should be further investigated for its clinical relevance. It appears that large contact size of the conditioning-stimulus and use of single rather than dual test-stimulus pain contribute to augmentation of CPM reliability. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e

  15. Biodegradation of Jet Fuel-4 (JP-4) in Sequencing Batch Reactors

    Science.gov (United States)

    1992-06-01

    nalw~eo %CUMENTATION PAGE__ _ _ _ _ _ _ _ _O 74S Ab -A258 020 L AW POi~W6 DATI .~ TYP AIMqm ,-& 0 U. glbs A~ I ma"&LFUN Mu BIODEGRADATION OF JET FUEL...Specific Objectives of This Proposal Are: 1. To assess the ability of C. resinae , P. chrysosporium and selected bacterial consortia to degrade individual...chemical components of JP-4. 2. To develop a sequencing batch reactor that utilizes C. resinae to degrade chemical components of JP-4 in contaminated

  16. Conformance Testing of SGSF-064-1 Using CANoe

    Directory of Open Access Journals (Sweden)

    Intaek Kim

    2015-11-01

    Full Text Available In this paper, the authors describe a conformance testing system for SGSF-064-1, the communication protocol between electric vehicles and conductive DC (direct current chargers in Korea. Since the SGSF-064-1 is based on CAN (controller area network, the testing system was developed by CANoe. The DC charger known as EVSE (electric vehicle supply equipment is the system being tested and the developed system implemented in PC (personal computer. The developed system performs as a tester to ensure that the DC chargers from various manufactures can conform to the communication protocol in SGSF-064-1. The testing system contains four testing modes which also consist of several test cases.

  17. Strong decays of the 1 P and 2 D doubly charmed states

    Science.gov (United States)

    Xiao, Li-Ye; Lü, Qi-Fang; Zhu, Shi-Lin

    2018-04-01

    We perform a systematical investigation of the strong decay properties of the low-lying 1 P - and 2 D -wave doubly charmed baryons with the 3P0 quark pair creation model. The main predictions include: (i) in the Ξc c and Ωc c family, the 1 P ρ mode excitations with JP=1 /2- and 3 /2- should be the fairly narrow states, while, for the 1 P λ mode excitations, they are most likely to be moderate states with a width of Γ ˜100 MeV . (ii) The 2 Dρ ρ states mainly decay via emitting a heavy-light meson and the decay widths can reach several tens MeV if their masses are above the threshold of ΛcD or ΞcD , respectively. The 2 Dλ λ states may be broad states with a width of Γ >100 MeV .

  18. Effects of JP-8 Jet Fuel on Homeostasis of Clone 9 Rat Liver Cells

    Science.gov (United States)

    Wilson, C. L.; Barhoumi, R.; Burghardt, R.; Miladi, A.; Jung, A.

    2000-01-01

    Chronic exposure to JP-8 and other kerosene-based petroleum distillates has been associated with hepatic, renal, neurologic, pulmonary, and immune toxicity. However, the effects of kerosene-type jet fuels on cellular homeostasis hitherto have not been reported. Fluorescence imaging using a Meridian Ultima laser scanning fluorescence microscope was used to evaluate the effect of JP-8 jet fuel on a communication competent rat liver cell line. Several endpoints of cellular function were measured including gap junctional intercellular communication (GJIC), mitochondrial and plasma membrane potential (MMP and PMP, respectively), intracellular glutathione (GSH) concentration, glutathione-S-transferase (GST) activity, and reactive oxygen species (ROS) generation. Cells were treated with JP-8 (0.01 to 2% in ethanol (EtOH)) for the following time points: 1 h, 24 h, 48 h, and analysis immediately after addition of jet fuel. GJIC analyzed directly after addition of 1% JP-8 was reduced 4.9-fold relative to EtOH-dosed control groups and further reduction (12.6-fold) was observed in cells treated for 1 h. Moreover, GJIC was not recoverable in cells treated with 1% JP-8 for 1 h and subsequently washed and incubated in fresh medium for 1 h. Significant changes in GSH content and GST activity were observed in cells analyzed directly after addition of 1% JP-8. GSH content increased in cells treated for 1 h with less than 2% JP-8 whereas treatment with 2% JP-8 for 1 h resulted in a 50% reduction in intracellular GSH relative to EtOH-dosed controls. Cells treated with 1% JP-8 for 48 h exhibited changes in GSH levels. However, higher JP-8 concentrations exhibited more pronounced changes in GSH and GST, which led to suppression of GSH synthesis. ROS increased in a dose-responsive fashion at JP-8 concentrations up to 1%, but decreased to 80% of control values at 2% and 3% JP-8. A 25% reduction in PMP was observed in cells treated for 1 h with 1% JP-8. In contrast, cells treated for 48 h

  19. Combustion of High Molecular Weight Hydrocarbon Fuels and JP-8 at Moderate Pressures

    Science.gov (United States)

    2016-07-26

    1. Introduction Fundamental knowledge of mechanisms of autoignition of condensed hydrocarbon fuels at elevated pressures is essential for accurate...particular JP-8) and surrogates of jet-fuels in laminar non-uniform flows at elevated pressures upto 2.5 MPa. Experimental and kinetic modeling studies...AGENCY NAME(S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 Combustion, Jet Fuels, JP-8, Elevated

  20. Effects of aerosol-vapor JP-8 jet fuel on the functional observational battery, and learning and memory in the rat.

    Science.gov (United States)

    Baldwin, C M; Houston, F P; Podgornik, M N; Young, R S; Barnes, C A; Witten, M L

    2001-01-01

    To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.

  1. Development of a comprehensive performance-testing protocol for competitive surfers.

    Science.gov (United States)

    Sheppard, Jeremy M; Nimphius, Sophia; Haff, Greg G; Tran, Tai T; Spiteri, Tania; Brooks, Hedda; Slater, Gary; Newton, Robert U

    2013-09-01

    Appropriate and valid testing protocols for evaluating the physical performances of surfing athletes are not well refined. The purpose of this project was to develop, refine, and evaluate a testing protocol for use with elite surfers, including measures of anthropometry, strength and power, and endurance. After pilot testing and consultation with athletes, coaches, and sport scientists, a specific suite of tests was developed. Forty-four competitive junior surfers (16.2 ± 1.3 y, 166.3 ± 7.3 cm, 57.9 ± 8.5 kg) participated in this study involving a within-day repeated-measures analysis, using an elite junior group of 22 international competitors (EJG), to establish reliability of the measures. To reflect validity of the testing measures, a comparison of performance results was then undertaken between the EJG and an age-matched competitive junior group of 22 nationally competitive surfers (CJG). Percent typical error of measurement (%TEM) for primary variables gained from the assessments ranged from 1.1% to 3.0%, with intraclass correlation coefficients ranging from .96 to .99. One-way analysis of variance revealed that the EJG had lower skinfolds (P = .005, d = 0.9) than the CJG, despite no difference in stature (P = .102) or body mass (P = .827). The EJG were faster in 15-m sprint-paddle velocity (P < .001, d = 1.3) and had higher lower-body isometric peak force (P = .04, d = 0.7) and superior endurance-paddling velocity (P = .008, d = 0.9). The relatively low %TEM of these tests in this population allows for high sensitivity to detect change. The results of this study suggest that competitively superior junior surfers are leaner and possess superior strength, paddling power, and paddling endurance.

  2. Analysis list: SETDB1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SETDB1 Blood,Bone,Epidermis + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/...target/SETDB1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/SETDB1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/SETDB1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/SETDB1....Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/SETDB1.Bone.tsv,http://dbarchive.bioscienc...edbc.jp/kyushu-u/hg19/colo/SETDB1.Epidermis.tsv http://dbarchive.biosciencedbc.jp/k

  3. Analysis list: FLI1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available FLI1 Blood,Bone,Muscle + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/targe...t/FLI1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/FLI1.5.tsv http://dbarchive.biosciencedb...c.jp/kyushu-u/hg19/target/FLI1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/FLI1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/FLI1.Bone.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/FLI1.Muscle.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Bl

  4. Analysis list: nfya-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available nfya-1 Adult,Embryo,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/t...arget/nfya-1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/nfya-1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/target/nfya-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/nfya-1....Adult.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/nfya-1.Embryo.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/ce10/colo/nfya-1.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyu

  5. Analysis list: Foxa1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Foxa1 Gonad,Kidney,Liver,Lung,Prostate + mm9 http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/Foxa1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Foxa1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Foxa1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Fox...a1.Gonad.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Foxa1.Kidney.tsv,http://dbarchive.bioscie...ncedbc.jp/kyushu-u/mm9/colo/Foxa1.Liver.tsv,http://dbarchive.biosciencedbc.jp/kyush

  6. Analysis list: PBX1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available PBX1 Blood,Breast,Digestive tract + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u.../hg19/target/PBX1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/PBX1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/PBX1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/PBX1.B...lood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/PBX1.Breast.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/PBX1.Digestive_tract.tsv http://dbarchive.biosciencedbc.jp

  7. Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

    Science.gov (United States)

    Palmerini, Emanuela; Agostinelli, Claudio; Picci, Piero; Pileri, Stefano; Marafioti, Teresa; Lollini, Pier-Luigi; Scotlandi, Katia; Longhi, Alessandra; Benassi, Maria Serena; Ferrari, Stefano

    2017-12-19

    We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome. Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases. Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.

  8. Analysis list: ELK1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ELK1 Blood,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ELK1.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ELK1.5.tsv http://dbarchive.biosciencedbc.jp/...kyushu-u/hg19/target/ELK1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ELK1.Blood.tsv,http://...dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ELK1.Uterus.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  9. Analysis list: RB1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available RB1 Prostate,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/R...B1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/RB1.5.tsv http://dbarchive.biosciencedbc.jp/...kyushu-u/hg19/target/RB1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/RB1.Prostate.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/RB1.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Prostate.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  10. Analysis list: ama-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ama-1 Adult,Embryo + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/am...a-1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/ama-1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/ce10/target/ama-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/ama-1.Adult.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/ama-1.Embryo.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/Adult.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Embryo.gml ...

  11. Analysis list: AGO1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available AGO1 Breast,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/...AGO1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/AGO1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/AGO1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/AGO1.Breast.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/AGO1.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Breast.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Prostate.gml ...

  12. Analysis list: HDAC1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HDAC1 Blood,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/...HDAC1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HDAC1.5.tsv http://dbarchive.biosciencedb...c.jp/kyushu-u/hg19/target/HDAC1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HDAC1.Blood.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/hg19/colo/HDAC1.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Prostate.gml ...

  13. Analysis list: ces-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ces-1 Embryo,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/c...es-1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/ces-1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/ce10/target/ces-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/ces-1.Embryo.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/ce10/colo/ces-1.Larvae.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  14. Analysis list: Irf1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Irf1 Blood,Digestive tract + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/tar...get/Irf1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Irf1.5.tsv http://dbarchive.bioscienced...bc.jp/kyushu-u/mm9/target/Irf1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Irf1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Irf1.Digestive_tract.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Digestive_tract.gml ...

  15. Analysis list: ARRB1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ARRB1 Blood,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/...ARRB1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ARRB1.5.tsv http://dbarchive.biosciencedb...c.jp/kyushu-u/hg19/target/ARRB1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ARRB1.Blood.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/hg19/colo/ARRB1.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Prostate.gml ...

  16. Analysis list: WWTR1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available WWTR1 Breast,Liver + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/WW...TR1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/WWTR1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/WWTR1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/WWTR1.Breast.tsv,http://dbarchive.bioscienc...edbc.jp/kyushu-u/hg19/colo/WWTR1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Breast.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Liver.gml ...

  17. Analysis list: CTBP1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available CTBP1 Breast,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target.../CTBP1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/CTBP1.5.tsv http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/target/CTBP1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/CTBP1.Breast.tsv,http://dbarchive.biosci...encedbc.jp/kyushu-u/hg19/colo/CTBP1.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Breast.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Prostate.gml ...

  18. Analysis list: blmp-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available blmp-1 Embryo,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/...blmp-1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/blmp-1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/target/blmp-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/blmp-1.Embryo....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/blmp-1.Larvae.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  19. Analysis list: JIL-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available JIL-1 Cell line,Larvae + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/...JIL-1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/JIL-1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/dm3/target/JIL-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/JIL-1.Cell_line.tsv,http://dbarchive.bioscie...ncedbc.jp/kyushu-u/dm3/colo/JIL-1.Larvae.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/dm3/colo/Cell_line.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Larvae.gml ...

  20. Analysis list: Hsf1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Hsf1 Gonad,Neural + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hsf1....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hsf1.5.tsv http://dbarchive.biosciencedbc.jp/kyu...shu-u/mm9/target/Hsf1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hsf1.Gonad.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Hsf1.Neural.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Gonad.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Neural.gml ...

  1. Analysis list: Fli1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Fli1 Blood,Embryo + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Fli1....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Fli1.5.tsv http://dbarchive.biosciencedbc.jp/kyu...shu-u/mm9/target/Fli1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Fli1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Fli1.Embryo.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Embryo.gml ...

  2. Analysis list: EBF1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available EBF1 Adipocyte,Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/...EBF1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/EBF1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/EBF1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/EBF1.Adipocyte.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/hg19/colo/EBF1.Blood.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Adipocyte.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  3. Analysis list: tra-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available tra-1 Adult,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/tr...a-1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/tra-1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/ce10/target/tra-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/tra-1.Adult.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/tra-1.Larvae.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/Adult.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  4. Analysis list: HCFC1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HCFC1 Blood,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HC...FC1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HCFC1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/HCFC1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HCFC1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/HCFC1.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  5. Analysis list: Wt1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Wt1 Embryo,Kidney + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Wt1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Wt1.5.tsv http://dbarchive.biosciencedbc.jp/kyush...u-u/mm9/target/Wt1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Wt1.Embryo.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Wt1.Kidney.tsv http://dbarchive.biosciencedb...c.jp/kyushu-u/mm9/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Kidney.gml ...

  6. Analysis list: Twist1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Twist1 Embryo,Neural + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Tw...ist1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Twist1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/target/Twist1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Twist1.Embryo.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/mm9/colo/Twist1.Neural.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Neural.gml ...

  7. Analysis list: ASCL1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ASCL1 Epidermis,Others + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/targe...t/ASCL1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ASCL1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/ASCL1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ASCL1.Epidermi...s.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ASCL1.Others.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Epidermis.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Others.gml ...

  8. Analysis list: msl-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available msl-1 Cell line,Larvae + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/msl-1.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/msl-1.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/dm3/target/msl-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/msl-1.Cell_line.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/msl-1.Larvae.tsv http://dbar...chive.biosciencedbc.jp/kyushu-u/dm3/colo/Cell_line.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Larvae.gml ...

  9. Analysis list: Nfatc1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Nfatc1 Epidermis,Pancreas + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/targ...et/Nfatc1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nfatc1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Nfatc1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nfatc1.Epider...mis.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nfatc1.Pancreas.tsv http://dbarchive.bioscienc...edbc.jp/kyushu-u/mm9/colo/Epidermis.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pancreas.gml ...

  10. Analysis list: CREB1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available CREB1 Blood,Digestive tract,Liver,Pluripotent stem cell,Prostate,Uterus + hg19 http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/CREB1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/CRE...B1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/CREB1.10.tsv http://dbarchive.b...iosciencedbc.jp/kyushu-u/hg19/colo/CREB1.Blood.tsv,http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/colo/CREB1.Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/CREB1.

  11. Analysis list: IRF1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available IRF1 Adipocyte,Blood,Digestive tract + hg19 http://dbarchive.biosciencedbc.jp/kyush...u-u/hg19/target/IRF1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/IRF1.5.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/hg19/target/IRF1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/IRF1.Adipocyte.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/IRF1.Blood.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/IRF1.Digestive_tract.tsv http://dbarchive.bioscience

  12. Analysis list: Ncor1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Ncor1 Blood,Embryonic fibroblast,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/Ncor1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ncor1.5.tsv http://dbarchi...ve.biosciencedbc.jp/kyushu-u/mm9/target/Ncor1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ncor1.Blood.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ncor1.Embryonic_fibroblast.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ncor1.Liver.tsv http://dbarchive.bioscien

  13. Analysis list: FOXO1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available FOXO1 Blood,Digestive tract,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-...u/hg19/target/FOXO1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/FOXO1.5.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/hg19/target/FOXO1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/FOXO1.Blood.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/FOXO1.Digestive_tract.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/FOXO1.Uterus.tsv http://dbarchive.bioscienc

  14. 13 September 2013 - Chairman of the Board of Directors of the von Karman Institute Kingdom of Belgium J.-P. Contzen visiting the ATLAS experimental cavern with ATLAS Former Spokesperson P. Jenni; visiting the LHC tunnel at Point 1 with Technology Department N. Delruelle and signing the guest book with Technology Department Head F. Bordry. International Relations Adviser T. Kurtyka present.

    CERN Multimedia

    Laurent Egli (visit)

    2013-01-01

    13 September 2013 - Chairman of the Board of Directors of the von Karman Institute Kingdom of Belgium J.-P. Contzen visiting the ATLAS experimental cavern with ATLAS Former Spokesperson P. Jenni; visiting the LHC tunnel at Point 1 with Technology Department N. Delruelle and signing the guest book with Technology Department Head F. Bordry. International Relations Adviser T. Kurtyka present.

  15. Analysis list: TEAD1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available TEAD1 Digestive tract,Liver,Neural + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TEA...D1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TEAD1.5.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/hg19/target/TEAD1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TEA...D1.Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TEAD...1.Liver.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TEAD1.Neural.tsv http://dbarchive.bioscienc

  16. Analysis list: BMI1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available BMI1 Blood,Digestive tract,Neural,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/BMI...1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/BMI1.5.tsv http://db...archive.biosciencedbc.jp/kyushu-u/hg19/target/BMI1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/BMI...1.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/BMI1.Diges...tive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/BMI1.Neural.tsv,http://dbarchive.bioscie

  17. Analysis list: Men1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Men1 Blood,Muscle,Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyu...shu-u/mm9/target/Men1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Men1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Men1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Men1....Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Men1.Muscle.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Men1.Pluripotent_stem_cell.tsv http://dbarchive.bioscienced

  18. Analysis list: Rpa1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Rpa1 Blood,Embryonic fibroblast,Spleen + mm9 http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/Rpa1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Rpa1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Rpa1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Rpa1.B...lood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Rpa1.Embryonic_fibro...blast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Rpa1.Spleen.tsv http://dbarchive.biosciencedbc

  19. Analysis list: Pbx1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pbx1 Embryo,Embryonic fibroblast,Muscle + mm9 http://dbarchive.biosciencedbc.jp/kyu...shu-u/mm9/target/Pbx1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Pbx1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Pbx1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pbx1....Embryo.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pbx1.Embryonic_fib...roblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pbx1.Muscle.tsv http://dbarchive.bioscienced

  20. Analysis list: Tal1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Tal1 Blood,Embryo,Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyu...shu-u/mm9/target/Tal1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Tal1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Tal1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Tal1....Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Tal1.Embryo.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Tal1.Pluripotent_stem_cell.tsv http://dbarchive.bioscienced

  1. Analysis list: RUNX1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available RUNX1 Blood,Digestive tract,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyush...u-u/hg19/target/RUNX1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/RUNX1.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/RUNX1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/...RUNX1.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/RUNX1.Digest...ive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/RUNX1.Prostate.tsv http://dbarchive.bioscience

  2. Analysis list: HSF1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HSF1 Adipocyte,Blood,Bone,Breast,Digestive tract,Epidermis,Liver + hg19 http://dbar...chive.biosciencedbc.jp/kyushu-u/hg19/target/HSF1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HSF1.5.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HSF1.10.tsv http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/colo/HSF1.Adipocyte.tsv,http://dbarchive.biosciencedbc.jp/kyu...shu-u/hg19/colo/HSF1.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HSF1.Bone.tsv,http://dba

  3. Analysis list: Brca1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Brca1 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Brca1.1.tsv... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Brca1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Brca1....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Brca1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

  4. Analysis list: hda-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available hda-1 Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/hda-1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/hda-1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/hda...-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/hda-1.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  5. Analysis list: DICER1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DICER1 + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/DICER1.1.tsv h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/DICER1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/DICER...1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/DICER1..tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/.gml ...

  6. Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

    International Nuclear Information System (INIS)

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-01-01

    Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  7. Alternative Bio-Derived JP-8 Class Fuel and JP-8 Fuel: Flame Tube Combustor Test Results Compared using a GE TAPS Injector Configuration

    Science.gov (United States)

    Hicks, Yolanda R.; Anderson, Robert; Tedder, Sarah

    2016-01-01

    This paper presents results from tests in a NASA Glenn Research Center (GRC) flame tube facility, where a bio-derived alternate fuel was compared with JP-8 for emissions and general combustion performance. A research version of General Electric Aviation (GE) TAPS injector was used for the tests. Results include 2D, planar laser-based imaging as well as basic flow visualization of the flame. Four conditions were selected that simulate various engine power conditions relevant to NASA Fundamental Aeronautics Supersonics and Environmentally Responsible Aviation Projects were tested.

  8. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    Science.gov (United States)

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Analysis list: WHSC1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available WHSC1 Blood,Digestive tract + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/WHS...C1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/WHSC1.5.tsv http://dbarchive.biosc...iencedbc.jp/kyushu-u/hg19/target/WHSC1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/WHSC1.Blo...od.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/WHSC1.Digestive_tract

  10. Analysis list: TLX1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available TLX1 Blood,Digestive tract + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TLX...1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TLX1.5.tsv http://dbarchive.bioscien...cedbc.jp/kyushu-u/hg19/target/TLX1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TLX1.Blood.ts...v,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TLX1.Digestive_tract.tsv h

  11. Analysis list: Taf1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Taf1 Blood,Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Taf...1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Taf1.5.tsv http://dbarchive.biosc...iencedbc.jp/kyushu-u/mm9/target/Taf1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Taf1.Blood.t...sv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Taf1.Pluripotent_stem_cell

  12. Analysis list: Hdac1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Hdac1 Muscle,Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hda...c1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hdac1.5.tsv http://dbarchive.b...iosciencedbc.jp/kyushu-u/mm9/target/Hdac1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hdac1.M...uscle.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hdac1.Pluripotent_s

  13. Analysis list: Snai1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Snai1 Breast,Muscle + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Sna...i1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Snai1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Sna...i1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Snai1.Breast.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Snai1.Muscle.tsv http://dbarchive.

  14. Analysis list: Egr1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Egr1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Eg...r1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Egr1.Blood.tsv,http://dbarch...ive.biosciencedbc.jp/kyushu-u/mm9/colo/Egr1.Liver.tsv http://dbarchive.bioscience

  15. Analysis list: NOTCH1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NOTCH1 Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTC...H1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NOTCH1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  16. Analysis list: alr-1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available alr-1 Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/alr-1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/alr-1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/al...r-1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/alr-1.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  17. Analysis list: HECTD1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HECTD1 Breast + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HECTD1....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HECTD1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HECT...D1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HECTD1.Breast.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Breast.gml ...

  18. Analysis list: Ets1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Ets1 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ets1.1.tsv h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ets1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Et...s1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ets1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

  19. Protocol - RPD | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...e version) File URL: ftp://ftp.biosciencedbc.jp/archive/rpd/LATEST/rpd_protocol_jp.zip File size: 535 KB Fil...e name: rpd_protocol_en.zip (English version) File URL: ftp://ftp.biosciencedbc.jp/archiv...tabase Database Description Download License Update History of This Database Site Policy | Contact Us Protocol - RPD | LSDB Archive ...

  20. Presence of pRI1:

    DEFF Research Database (Denmark)

    Migura, Lourdes Garcia; Hasman, Henrik; Jensen, Lars Bogø

    2009-01-01

    This study focused on the molecular characterization of a small cryptic, mobilizable plasmid (6038 bp) sequenced from an E. faecium 9631160-1 of poultry origin. Sequence analysis of pRI1 revealed seven open reading frames. pRI1 contained an IS 100% identical to ISEfa4. This insertion element...... almost identical to the repA from the pEFNP1 and pKQ10 plasmids from E. faecium was also identified. Presence of the pRI1 replication initiation gene (rep) was analyzed in a panel of 159 E. faecium isolates of human and animal origin from different European countries, of which 60 tested positive...

  1. Analysis list: Hif1a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Hif1a Blood,Embryo + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hif1a.1.tsv http://dbarchi...ve.biosciencedbc.jp/kyushu-u/mm9/target/Hif1a.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hi...f1a.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hif1a.Blood.tsv,http://dbarchi...ve.biosciencedbc.jp/kyushu-u/mm9/colo/Hif1a.Embryo.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Embryo.gml ...

  2. Analysis list: DYRK1A [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DYRK1A Neural,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/...DYRK1A.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/DYRK1A.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/DYRK1A.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/DYRK1A.Neural....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/DYRK1A.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Neural.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  3. The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁ and hypertension (S1P₃ in rat.

    Directory of Open Access Journals (Sweden)

    Ryan M Fryer

    Full Text Available Sphingosine-1-phospate (S1P and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X receptor agonist produces modest hypertension in patients (2-3 mmHg in 1-yr trial as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension, and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P₁,₅ agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min elicited acute bradycardia in anesthetized rats demonstrating an S1P₁ mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls, BAF312 (0.3, 3.0, 30.0 mg/kg/d had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P₃ receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P₁ receptors mediate bradycardia while hypertension is mediated by S1P₃ receptor activation.

  4. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  5. Validation of IEEE P1547.1 Interconnection Test Procedures: ASCO 7000 Soft Load Transfer System

    Energy Technology Data Exchange (ETDEWEB)

    Kroposki, B.; Englebretson, S.; Pink, C.; Daley, J.; Siciliano, R.; Hinton, D.

    2003-09-01

    This report presents the preliminary results of testing the ASCO 7000 Soft Load Transfer System according to IEEE P1547.1 procedures. The ASCO system interconnects synchronous generators with the electric power system and provides monitoring and control for the generator and grid connection through extensive protective functions. The purpose of this testing is to evaluate and give feedback on the contents of IEEE Draft Standard P1547.1 Conformance Tests Procedures for Equipment Interconnecting Distributed Resources With Electric Power Systems.

  6. Prospective evaluation of a new protocol for the provisional use of perfusion imaging with exercise stress testing

    Energy Technology Data Exchange (ETDEWEB)

    Duvall, W.L. [Hartford Hospital, Division of Cardiology (Henry Low Heart Center), Hartford, CT (United States); Mount Sinai Medical Center, Division of Cardiology (Mount Sinai Heart), New York, NY (United States); Savino, John A.; Levine, Elliot J.; Croft, Lori B.; Henzlova, Milena J. [Mount Sinai Medical Center, Division of Cardiology (Mount Sinai Heart), New York, NY (United States); Hermann, Luke K. [Mount Sinai Medical Center, Department of Emergency Medicine, New York, NY (United States)

    2014-11-04

    Previous literature suggests that myocardial perfusion imaging (MPI) adds little to the prognosis of patients who exercise >10 metabolic equivalents (METs) during stress testing. With this in mind, we prospectively tested a provisional injection protocol in emergency department (ED) patients presenting for the evaluation of chest pain in which a patient would not receive an injection of radioisotope if adequate exercise was achieved without symptoms and a negative ECG response. All patients who presented to the ED over a 5-year period who were referred for stress testing as part of their ED evaluation were included. Patients considered for a provisional protocol were: exercise stress, age <65 years, no known coronary artery disease, and an interpretable rest ECG. Criteria for not injecting included a maximal predicted heart rate ≥85 %, ≥10 METs of exercise, no anginal symptoms during stress, and no ECG changes. Groups were compared based on stress test results, all-cause and cardiac mortality, follow-up cardiac testing, subsequent revascularization, and cost. A total of 965 patients were eligible with 192 undergoing exercise-only and 773 having perfusion imaging. After 41.6 ± 19.6 months of follow-up, all-cause mortality was similar in the exercise-only versus the exercise plus imaging group (2.6 % vs. 2.1 %, p = 0.59). There were no cardiac deaths in the exercise-only group. At 1 year there was no difference in the number of repeat functional stress tests (1.6 % vs. 2.1 %, p = 0.43), fewer angiograms (0 % vs. 4.0 %, p = 0.002), and a significantly lower cost (65 ± 332 vs 506 ± 1,991, p = 0.002; values are in US dollars) in the exercise-only group. The radiation exposure in the exercise plus imaging group was 8.4 ± 2.1 mSv. A provisional injection protocol has a very low mortality, few follow-up diagnostic tests, and lower cost compared to standard imaging protocols. If adopted it would decrease radiation exposure, save time and decrease health-care costs

  7. Prospective evaluation of a new protocol for the provisional use of perfusion imaging with exercise stress testing

    International Nuclear Information System (INIS)

    Duvall, W.L.; Savino, John A.; Levine, Elliot J.; Croft, Lori B.; Henzlova, Milena J.; Hermann, Luke K.

    2015-01-01

    Previous literature suggests that myocardial perfusion imaging (MPI) adds little to the prognosis of patients who exercise >10 metabolic equivalents (METs) during stress testing. With this in mind, we prospectively tested a provisional injection protocol in emergency department (ED) patients presenting for the evaluation of chest pain in which a patient would not receive an injection of radioisotope if adequate exercise was achieved without symptoms and a negative ECG response. All patients who presented to the ED over a 5-year period who were referred for stress testing as part of their ED evaluation were included. Patients considered for a provisional protocol were: exercise stress, age <65 years, no known coronary artery disease, and an interpretable rest ECG. Criteria for not injecting included a maximal predicted heart rate ≥85 %, ≥10 METs of exercise, no anginal symptoms during stress, and no ECG changes. Groups were compared based on stress test results, all-cause and cardiac mortality, follow-up cardiac testing, subsequent revascularization, and cost. A total of 965 patients were eligible with 192 undergoing exercise-only and 773 having perfusion imaging. After 41.6 ± 19.6 months of follow-up, all-cause mortality was similar in the exercise-only versus the exercise plus imaging group (2.6 % vs. 2.1 %, p = 0.59). There were no cardiac deaths in the exercise-only group. At 1 year there was no difference in the number of repeat functional stress tests (1.6 % vs. 2.1 %, p = 0.43), fewer angiograms (0 % vs. 4.0 %, p = 0.002), and a significantly lower cost (65 ± 332 vs 506 ± 1,991, p = 0.002; values are in US dollars) in the exercise-only group. The radiation exposure in the exercise plus imaging group was 8.4 ± 2.1 mSv. A provisional injection protocol has a very low mortality, few follow-up diagnostic tests, and lower cost compared to standard imaging protocols. If adopted it would decrease radiation exposure, save time and decrease health-care costs

  8. JP-8 jet fuel can promote auditory impairment resulting from subsequent noise exposure in rats.

    Science.gov (United States)

    Fechter, Laurence D; Gearhart, Caroline; Fulton, Sherry; Campbell, Jerry; Fisher, Jeffrey; Na, Kwangsam; Cocker, David; Nelson-Miller, Alisa; Moon, Patrick; Pouyatos, Benoit

    2007-08-01

    We report on the transient and persistent effects of JP-8 jet fuel exposure on auditory function in rats. JP-8 has become the standard jet fuel utilized in the United States and North Atlantic Treaty Organization countries for military use and it is closely related to Jet A fuel, which is used in U.S. domestic aviation. Rats received JP-8 fuel (1000 mg/m(3)) by nose-only inhalation for 4 h and half of them were immediately subjected to an octave band of noise ranging between 97 and 105 dB in different experiments. The noise by itself produces a small, but permanent auditory impairment. The current permissible exposure level for JP-8 is 350 mg/m(3). Additionally, a positive control group received only noise exposure, and a fourth group consisted of untreated control subjects. Exposures occurred either on 1 day or repeatedly on 5 successive days. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. In other rats, tissues were harvested following JP-8 exposure for assessment of hydrocarbon levels or glutathione (GSH) levels. A single JP-8 exposure by itself at 1000 mg/m(3) did not disrupt auditory function. However, exposure to JP-8 and noise produced an additive disruption in outer hair cell function. Repeated 5-day JP-8 exposure at 1000 mg/m(3) for 4 h produced impairment of outer hair cell function that was most evident at the first postexposure assessment time. Partial though not complete recovery was observed over a 4-week postexposure period. The adverse effects of repeated JP-8 exposures on auditory function were inconsistent, but combined treatment with JP-8 + noise yielded greater impairment of auditory function, and hair cell loss than did noise by itself. Qualitative comparison of outer hair cell loss suggests an increase in outer hair cell death among rats treated with JP-8 + noise for 5 days as compared to noise alone. In most instances, hydrocarbon constituents of the fuel

  9. Analysis list: NR1H3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NR1H3 Adipocyte,Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target.../NR1H3.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NR1H3.5.tsv http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/target/NR1H3.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NR1H3.Adipocyte....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NR1H3.Blood.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Adipocyte.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  10. Analysis list: E2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/E2f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/E2f1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  11. Analysis list: NR3C1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NR3C1 Blood,Bone,Breast,Liver,Others,Prostate,Uterus + hg19 http://dbarchive.biosci...encedbc.jp/kyushu-u/hg19/target/NR3C1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NR3C1.5.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NR3C1.10.tsv http://dbarchive.biosciencedbc.jp/kyu...shu-u/hg19/colo/NR3C1.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NR3C1.Bone.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NR3C1.Breast.tsv,http://dbarchive.bi

  12. Comparison of test results in the evaluation of the WSF of several jet fuels using the standardized aquatic microcosm and the mixed flask culture protocols

    International Nuclear Information System (INIS)

    Landis, W.G.; Matthews, R.A.; Markiewicz, A.J.; Matthews, G.B.

    1993-01-01

    The water soluble fraction of the turbine fuels Jet-A, JP-4 and JP-8 have been examines as stressors for two microcosm protocols, the standardized aquatic microcosm (SAM) and the mixed flask culture (MFC). The SAM is a 3 L system inoculated with standard cultures of algae, zooplankton, bacteria, protozoa. In contrast, the MFC is 1 L and is inoculated with a complex mixture of organisms derived from a natural source. Analysis of the organism counts and physical data were conducted using conventional and newly derived multivariate methods. Physical parameters, such as pH and oxygen metabolism, were often not as sensitive as species and bacterial counts. Like the SAM system, species numbers and other variables that determined clusters varied among sampling dates. Compared to the larger yet simpler system, the MFC exhibits more violent dynamics and is more likely to become catastrophically fixated, as in systems dominated by cyanobacteria. The combination of greater diversity and smaller volume may contribute to the volatile or chaotic dynamics of the MFC system

  13. Software Modules for the Proximity-1 Space Link Interleaved Time Synchronization (PITS) Protocol

    Science.gov (United States)

    Woo, Simon S.; Veregge, John R.; Gao, Jay L.; Clare, Loren P.; Mills, David

    2012-01-01

    The Proximity-1 Space Link Interleaved Time Synchronization (PITS) protocol provides time distribution and synchronization services for space systems. A software prototype implementation of the PITS algorithm has been developed that also provides the test harness to evaluate the key functionalities of PITS with simulated data source and sink. PITS integrates time synchronization functionality into the link layer of the CCSDS Proximity-1 Space Link Protocol. The software prototype implements the network packet format, data structures, and transmit- and receive-timestamp function for a time server and a client. The software also simulates the transmit and receive-time stamp exchanges via UDP (User Datagram Protocol) socket between a time server and a time client, and produces relative time offsets and delay estimates.

  14. 1-RAAP: An Efficient 1-Round Anonymous Authentication Protocol for Wireless Body Area Networks.

    Science.gov (United States)

    Liu, Jingwei; Zhang, Lihuan; Sun, Rong

    2016-05-19

    Thanks to the rapid technological convergence of wireless communications, medical sensors and cloud computing, Wireless Body Area Networks (WBANs) have emerged as a novel networking paradigm enabling ubiquitous Internet services, allowing people to receive medical care, monitor health status in real-time, analyze sports data and even enjoy online entertainment remotely. However, because of the mobility and openness of wireless communications, WBANs are inevitably exposed to a large set of potential attacks, significantly undermining their utility and impeding their widespread deployment. To prevent attackers from threatening legitimate WBAN users or abusing WBAN services, an efficient and secure authentication protocol termed 1-Round Anonymous Authentication Protocol (1-RAAP) is proposed in this paper. In particular, 1-RAAP preserves anonymity, mutual authentication, non-repudiation and some other desirable security properties, while only requiring users to perform several low cost computational operations. More importantly, 1-RAAP is provably secure thanks to its design basis, which is resistant to the anonymous in the random oracle model. To validate the computational efficiency of 1-RAAP, a set of comprehensive comparative studies between 1-RAAP and other authentication protocols is conducted, and the results clearly show that 1-RAAP achieves the best performance in terms of computational overhead.

  15. 1-RAAP: An Efficient 1-Round Anonymous Authentication Protocol for Wireless Body Area Networks

    Directory of Open Access Journals (Sweden)

    Jingwei Liu

    2016-05-01

    Full Text Available Thanks to the rapid technological convergence of wireless communications, medical sensors and cloud computing, Wireless Body Area Networks (WBANs have emerged as a novel networking paradigm enabling ubiquitous Internet services, allowing people to receive medical care, monitor health status in real-time, analyze sports data and even enjoy online entertainment remotely. However, because of the mobility and openness of wireless communications, WBANs are inevitably exposed to a large set of potential attacks, significantly undermining their utility and impeding their widespread deployment. To prevent attackers from threatening legitimate WBAN users or abusing WBAN services, an efficient and secure authentication protocol termed 1-Round Anonymous Authentication Protocol (1-RAAP is proposed in this paper. In particular, 1-RAAP preserves anonymity, mutual authentication, non-repudiation and some other desirable security properties, while only requiring users to perform several low cost computational operations. More importantly, 1-RAAP is provably secure thanks to its design basis, which is resistant to the anonymous in the random oracle model. To validate the computational efficiency of 1-RAAP, a set of comprehensive comparative studies between 1-RAAP and other authentication protocols is conducted, and the results clearly show that 1-RAAP achieves the best performance in terms of computational overhead.

  16. Analysis list: Nr3c1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Nr3c1 Adipocyte,Blood,Breast,Embryo,Embryonic fibroblast,Liver,Neural + mm9 http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Nr3c1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/ta...rget/Nr3c1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr3c1.10.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Nr3c1.Adipocyte.tsv,http://dbarchive.biosciencedbc.jp.../kyushu-u/mm9/colo/Nr3c1.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr3c1.Breast.tsv,http://dbarchive.bioscience

  17. Aggregatibacter (Actinobacillus actimycetemcomitans leukotoxin and human periodontitis – A historic review with emphasis on JP2

    Directory of Open Access Journals (Sweden)

    Chi-Cheng Tsai

    2018-04-01

    Full Text Available Aggregatibacter (Actinobacillus actimycetemcomitans (Aa is a gram-negative bacterium that colonizes the human oral cavity and is causative agent for localized aggressive (juvenile periodontitis (AgP. In the middle of 1990s, a specific JP2 clone of belonging to the cluster of serotype b strains of Aa with highly leukotoxicity (leukotoxin, LtxA able to kill human immune cells was isolated. JP2 clone of Aa was strongly associated with in particularly in rapidly progressing forms of aggressive periodontitis. The JP2 clone of Aa is transmitted through close contacts. Therefore, AgP patients need intense monitoring of their periodontal status as the risk for developing severely progressing periodontitis lesions are relatively high. Furthermore, timely periodontal treatment, including periodontal surgery supplemented by the use of antibiotics, is warranted. More importantly, periodontal attachment loss should be prevented by early detection of the JP2 clone of Aa by microbial diagnosis testing and/or preventive means. Keywords: Aggregatibacter (Actinobacillus actinomycetemcomitans, Aggressive periodontitis, Leukotoxin (LtxA, Polymorphonuclear leukocytes (PMNs

  18. Superiority of visual (verbal) vs. auditory test presentation modality in a P300-based CIT: The Complex Trial Protocol for concealed autobiographical memory detection.

    Science.gov (United States)

    Deng, Xiaohong; Rosenfeld, J Peter; Ward, Anne; Labkovsky, Elena

    2016-07-01

    This paper continues our efforts to determine which modality is best for presentation of stimuli in the P300-based concealed information test (CIT) called the Complex Trial Protocol (CTP). The first part of the CTP trial involves presentation of the key probe or irrelevant stimuli, and is followed by presentation of target (T) or non-target (NT). In Rosenfeld et al. (2015), probes and irrelevants regularly alternated modality over trials, but Ts and NTs were always visual. In the present study, (in both its experiments, EXP 1 and EXP 2), probes and irrelevants alternated modalities on successive trials, as before. In present EXP 1, Ts and NTs were always auditory, but in EXP 2, they were simultaneously auditory and visual. Probe P300 data were different in each study: In Rosenfeld et al. (2015) and EXP 2 here, the bootstrap-based detection rates based on probe-minus-irrelevant differences, significantly differed favoring visual probe and irrelevant presentation modality. In EXP 1 here, detection rates were the same for the two modalities. In Rosenfeld et al. (2015) there was no main effect of probe modality, visual vs. auditory on probe-minus-irrelevant P300 difference. There were such effects here in EXP 1 (pvisual modality. Probe P300 latencies were shorter for visual than for auditory stimuli in Rosenfeld et al. (2015), a trend specifically reversed in the present pair of studies. RT was faster for visual stimuli in the present studies. The T and NT modality appears to interact with probe/irrelevant modality, and the best protocol for detecting concealed information is with the 2015 study protocol or that of EXP 2, using visual stimulus presentation. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Study of TiO2(1 1 0)-p(1x1), p(1x2) and p(1x3) surface structures by impact collision ion scattering spectroscopy (ICISS)

    International Nuclear Information System (INIS)

    Asari, E.; Souda, R.

    2000-01-01

    The surface structure of TiO 2 (1 1 0)-p(1x1), p(1x2) and p(1x3) were studied using impact collision ion scattering spectroscopy (ICISS). We found that (i) the height of bridging oxygen for the p(1x1) is comparative to that of bulk structure, (ii) the p(1x2) surface has the added Ti 2 O 3 unit rows proposed by Onishi et al. and also the oxygen atoms rows between Ti 2 O 3 unit rows and (iii) the p(1x3) surface is constructed with the same added Ti 2 O 3 unit rows as that in the p(1x2) surface, but the bridging oxygen rows exist between the Ti 2 O 3 unit rows

  20. Mixing of the lowest-lying qqq configurations with JP =1/2- in different hyperfine interaction models

    Science.gov (United States)

    Chen, Jia; An, Chunsheng; Chen, Hong

    2018-02-01

    We investigate mixing of the lowest-lying qqq configurations with JP = 1/2- caused by the hyperfine interactions between quarks mediated by Goldstone Boson Exchange, One Gluon Exchange, and both Goldstone Boson and One Gluon exchange, respectively. The first orbitally excited nucleon, Σ, Λ and Ξ states are considered. Contributions of both the contact term and tensor term are taken into account. Our numerical results show that mixing of the studied configurations in the two employed hyperfine interaction models are very different. Therefore, the present results, which should affect the strong and electromagnetic decays of baryon resonances, may be used to examine the present employed hyperfine interaction models. Supported by National Natural Science Foundation of China (11675131,11645002), Chongqing Natural Science Foundation (cstc2015jcyjA00032) and Fundamental Research Funds for the Central Universities (SWU115020)

  1. Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction.

    Science.gov (United States)

    Nakada, Tsutomu; Kashihara, Toshihide; Komatsu, Masatoshi; Kojima, Katsuhiko; Takeshita, Toshikazu; Yamada, Mitsuhiko

    2018-04-24

    Close physical association of Ca V 1.1 L-type calcium channels (LTCCs) at the sarcolemmal junctional membrane (JM) with ryanodine receptors (RyRs) of the sarcoplasmic reticulum (SR) is crucial for excitation-contraction coupling (ECC) in skeletal muscle. However, the molecular mechanism underlying the JM targeting of LTCCs is unexplored. Junctophilin 1 (JP1) and JP2 stabilize the JM by bridging the sarcolemmal and SR membranes. Here, we examined the roles of JPs in localization and function of LTCCs. Knockdown of JP1 or JP2 in cultured myotubes inhibited LTCC clustering at the JM and suppressed evoked Ca 2+ transients without disrupting JM structure. Coimmunoprecipitation and GST pull-down assays demonstrated that JPs physically interacted with 12-aa residues in the proximal C terminus of the Ca V 1.1. A JP1 mutant lacking the C terminus including the transmembrane domain (JP1ΔCT) interacted with the sarcolemmal/T-tubule membrane but not the SR membrane. Expression of this mutant in adult mouse muscles in vivo exerted a dominant-negative effect on endogenous JPs, impairing LTCC-RyR coupling at triads without disrupting JM morphology, and substantially reducing Ca 2+ transients without affecting SR Ca 2+ content. Moreover, the contractile force of the JP1ΔCT-expressed muscle was dramatically reduced compared with the control. Taken together, JPs recruit LTCCs to the JM through physical interaction and ensure robust ECC at triads in skeletal muscle.

  2. Dicty_cDB: Contig-U13840-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ( DQ493594 ) Mycoplasma alligatoris strain A21JP2 beta-galacto... 46 3.6 1 ( DU54...yloides stercoralis ... 46 3.6 1 ( FC820470 ) Sr_pAMT7_017m15_T7 S. ratti mixed stage pAMP Stro... 46 3.6 1

  3. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    Science.gov (United States)

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  4. Challenge of N95 and P100 Filtering Facepiece Respirators with Particles Containing Viable H1N1

    Science.gov (United States)

    2009-12-02

    test protocols have been previously described (2). Briefly, the LSAT is composed of 10-cm diameter stainless steel sanitary fittings and a 15-cm...coughing in Human Subjects. Journal of Aerosol Medicine 20:484-494. 15. WK19997: Standard test method for effectiveness of decontamination of air...facepiece respirator g gram(s) H1N1 a strain of influenza A identified by its hemagglutinin and neuraminindase Kr-85 a radioactive isotope of krypton

  5. Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

    Science.gov (United States)

    Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

    2017-02-01

    This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.

  6. Calculations of Edwards' pipe blowdown tests using the code TRAC P1

    International Nuclear Information System (INIS)

    O'Mahoney, R.

    1979-05-01

    The paper describes the results obtained using the non-thermal equilibrium LOCA code TRAC-P1 for two of a series of Pipe Blowdown Tests. Comparisons are made with the experimental values and RELAP-UK Mark IV predictions. Some discrepancies between prediction and experiment are observed, and certain aspects of the model are considered to warrant possible further attention. (U.K.)

  7. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

    Science.gov (United States)

    Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

    2015-06-01

    Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

  8. Chondroprotective Effects of a Standardized Extract (KBH-JP-040) from Kalopanax pictus, Hericium erinaceus, and Astragalus membranaceus in Experimentally Induced In Vitro and In Vivo Osteoarthritis Models.

    Science.gov (United States)

    Rahman, Md Mahbubur; Kim, Hyun-Kyu; Kim, Seong-Eun; Kim, Myung-Jin; Kim, Do-Hyung; Lee, Hak Sung

    2018-03-15

    The aim of this study was to investigate the chondroprotective effect of a standardized extract (KBH-JP-040) of the Korean traditional herbs Kalopanax pictus Castor-Aralia, Hericium erinaceus (Bull.) Persoon, and Astragalus membranaceus Schischkin on in vivo and in vitro osteoarthritis (OA) models. Cultured rat chondrocytes were pre-treated with KBH-JP-040 (50, 100 and 200 μg/mL) for 1 h, then recombinant human IL-1α (rhIL-1α) for 24 h. For the in vivo model, rabbits ( n = 60) were equally divided into experimental groups: normal control (NC), a collagenase-induced OA group, and OA groups treated with KBH-JP-040 (75, 100, and 150 mg/kg body weight) and celecoxib (Cx, 100 mg/kg) orally for 28 days. Treatment with KBH-JP-040 significantly attenuated inflammatory cytokines and matrix metalloproteinases (MMPs), suppressed the expression of IκBα, NF-κB, and JNK/p38 mitogen-activated protein (MAP) kinase, and upregulated aggrecan and collagen type-II expression in rhIL-1α-stimulated chondrocytes. Furthermore, the serum and synovial levels of inflammatory cytokines of rabbits also decreased in the treatment groups when compared with the OA group. Improved magnetic resonance imaging and histopathological findings further confirmed the therapeutic efficacy of KBH-JP-040 against OA. In conclusion, these results indicate that KBH-JP-040 possesses chondroprotective effects, suppressing inflammation and MMPs, and downregulating IκBα, NF-κB, and JNK/p38 MAP kinase-signaling pathways. This might be a potential therapeutic candidate for OA treatment.

  9. Chondroprotective Effects of a Standardized Extract (KBH-JP-040 from Kalopanax pictus, Hericium erinaceus, and Astragalus membranaceus in Experimentally Induced In Vitro and In Vivo Osteoarthritis Models

    Directory of Open Access Journals (Sweden)

    Md. Mahbubur Rahman

    2018-03-01

    Full Text Available The aim of this study was to investigate the chondroprotective effect of a standardized extract (KBH-JP-040 of the Korean traditional herbs Kalopanax pictus Castor-Aralia, Hericium erinaceus (Bull. Persoon, and Astragalus membranaceus Schischkin on in vivo and in vitro osteoarthritis (OA models. Cultured rat chondrocytes were pre-treated with KBH-JP-040 (50, 100 and 200 μg/mL for 1 h, then recombinant human IL-1α (rhIL-1α for 24 h. For the in vivo model, rabbits (n = 60 were equally divided into experimental groups: normal control (NC, a collagenase-induced OA group, and OA groups treated with KBH-JP-040 (75, 100, and 150 mg/kg body weight and celecoxib (Cx, 100 mg/kg orally for 28 days. Treatment with KBH-JP-040 significantly attenuated inflammatory cytokines and matrix metalloproteinases (MMPs, suppressed the expression of IκBα, NF-κB, and JNK/p38 mitogen-activated protein (MAP kinase, and upregulated aggrecan and collagen type-II expression in rhIL-1α-stimulated chondrocytes. Furthermore, the serum and synovial levels of inflammatory cytokines of rabbits also decreased in the treatment groups when compared with the OA group. Improved magnetic resonance imaging and histopathological findings further confirmed the therapeutic efficacy of KBH-JP-040 against OA. In conclusion, these results indicate that KBH-JP-040 possesses chondroprotective effects, suppressing inflammation and MMPs, and downregulating IκBα, NF-κB, and JNK/p38 MAP kinase-signaling pathways. This might be a potential therapeutic candidate for OA treatment.

  10. Evaluation excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si, and "1"1"3In(n,γ)"1"1"4"mIn reactions

    International Nuclear Information System (INIS)

    Zolotarev, K.I.

    2014-10-01

    Cross section data for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions are needed for solving a wide spectrum of scientific and technical tasks. The excitation function of "2"8Si(n,p)"2"8Al reaction refers to the nuclear data involved in fusion reactor design calculations. The "2"8Si(n,p)"2"8Al reaction is interesting also as the monitor reaction for measurements at fusion facilities. Activation detectors on the basis of the 31P(n,p)31Si reaction are commonly used in the reactor dosimetry. The "1"1"3In(n,γ)"1"1"4"mIn reaction is promising regarding reactor dosimetry application for two reasons. First, due to the "1"1"4"mIn decay parameters which are rather suitable for activation measurements. Half-life of "1"1"4"mIn is equal to T_1/_2 = (49.51 ± 0.01) days and gamma spectrum accompanying decay has only one line with energy 190.27 keV and intensity (15.56 ± 0.15)%. Second, the "1"1"3In(n,γ)"1"1"4"mIn reaction rate may be measured by using one activation detector simultaneously with the "1"1"5In(n,γ)"1"1"6"mIn reaction. Preliminary analysis of existing evaluated excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions show that new evaluations are needed for all above mentioned reactions. This report is devoted to the preparation of the new evaluations of cross sections data and related covariance matrixes of uncertainties for the "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions.

  11. Transitioning Adolescents and Young Adults With HIV Infection to Adult Care: Pilot Testing the "Movin' Out" Transitioning Protocol.

    Science.gov (United States)

    Maturo, Donna; Powell, Alexis; Major-Wilson, Hannah; Sanchez, Kenia; De Santis, Joseph P; Friedman, Lawrence B

    2015-01-01

    Advances in care and treatment of adolescents/young adults with HIV infection have made survival into adulthood possible, requiring transition to adult care. Researchers have documented that the transition process is challenging for adolescents/young adults. To ensure successful transition, a formal transition protocol is needed. Despite existing research, little quantitative evaluation of the transition process has been conducted. The purpose of the study was to pilot test the "Movin' Out" Transitioning Protocol, a formalized protocol developed to assist transition to adult care. A retrospective medical/nursing record review was conducted with 38 clients enrolled in the "Movin' Out" Transitioning Protocol at a university-based adolescent medicine clinic providing care to adolescents/young adults with HIV infection. Almost half of the participants were able to successfully transition to adult care. Reasons for failure to transition included relocation, attrition, lost to follow-up, and transfer to another adult service. Failure to transition to adult care was not related to adherence issues, X(2) (1, N=38)=2.49, p=.288; substance use, X(2) (1, N=38)=1.71, p=.474; mental health issues, X(2) (1, N=38)=2.23, p=.322; or pregnancy/childrearing, X(2) (1, N=38)=0.00, p=.627). Despite the small sample size, the "Movin' Out" Transitioning Protocol appears to be useful in guiding the transition process of adolescents/young adults with HIV infection to adult care. More research is needed with a larger sample to fully evaluate the "Movin' Out" Transitioning Protocol. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR

    Directory of Open Access Journals (Sweden)

    Pricila da Silva Cunha

    2014-01-01

    Full Text Available Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH, which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36: PRKCZ and SKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescent in situ hybridization (FISH, and/or multiplex ligation-dependent probe amplification (MLPA all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR of PRKCZ and SKI is a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs.

  13. Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

    Science.gov (United States)

    Dai, Lan; Liu, Yixuan; Xie, Lei; Wu, Xia; Qiu, Lihua; Di, Wen

    2017-09-26

    Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR 1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro , the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR 1 and S1PR 3 , but not S1PR 2 . Furthermore, inhibition of S1PR 1/3 , but not S1PR 2 , attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo , blockage of SphK or S1PR 1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR 1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

  14. Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

    Science.gov (United States)

    Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  15. Arithmetically Cohen-Macaulay sets of points in P^1 x P^1

    CERN Document Server

    Guardo, Elena

    2015-01-01

    This brief presents a solution to the interpolation problem for arithmetically Cohen-Macaulay (ACM) sets of points in the multiprojective space P^1 x P^1.  It collects the various current threads in the literature on this topic with the aim of providing a self-contained, unified introduction while also advancing some new ideas.  The relevant constructions related to multiprojective spaces are reviewed first, followed by the basic properties of points in P^1 x P^1, the bigraded Hilbert function, and ACM sets of points.  The authors then show how, using a combinatorial description of ACM points in P^1 x P^1, the bigraded Hilbert function can be computed and, as a result, solve the interpolation problem.  In subsequent chapters, they consider fat points and double points in P^1 x P^1 and demonstrate how to use their results to answer questions and problems of interest in commutative algebra.  Throughout the book, chapters end with a brief historical overview, citations of related results, and, where relevan...

  16. Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

    Directory of Open Access Journals (Sweden)

    Evgeny V Berdyshev

    Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.

  17. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

    Science.gov (United States)

    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

  18. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

    Science.gov (United States)

    Tsai, Hsing-Chuan; Han, May H

    2016-07-01

    Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

  19. Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

    Science.gov (United States)

    Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

    2011-01-01

    Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987

  20. [Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

    Science.gov (United States)

    Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

    2016-05-24

    To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

  1. The impact of a massive transfusion protocol (1:1:1) on major hepatic injuries: does it increase abdominal wall closure rates?

    Science.gov (United States)

    Ball, Chad G; Dente, Christopher J; Shaz, Beth; Wyrzykowski, Amy D; Nicholas, Jeffrey M; Kirkpatrick, Andrew W; Feliciano, David V

    2013-10-01

    Massive transfusion protocols (MTPs) using high plasma and platelet ratios for exsanguinating trauma patients are increasingly popular. Major liver injuries often require massive resuscitations and immediate hemorrhage control. Current published literature describes outcomes among patients with mixed patterns of injury. We sought to identify the effects of an MTP on patients with major liver trauma. Patients with grade 3, 4 or 5 liver injuries who required a massive blood component transfusion were analyzed. We compared patients with high plasma:red blood cell:platelet ratio (1:1:1) transfusions (2007-2009) with patients injured before the creation of an institutional MTP (2005-2007). Among 60 patients with major hepatic injuries, 35 (58%) underwent resuscitation after the implementation of an MTP. Patient and injury characteristics were similar between cohorts. Implementation of the MTP significantly improved plasma: red blood cell:platelet ratios and decreased crystalloid fluid resuscitation (p = 0.026). Rapid improvement in early acidosis and coagulopathy was superior with an MTP (p = 0.009). More patients in the MTP group also underwent primary abdominal fascial closure during their hospital stay (p = 0.021). This was most evident with grade 4 injuries (89% vs. 14%). The mean time to fascial closure was 4.2 days. The overall survival rate for all major liver injuries was not affected by an MTP (p = 0.61). The implementation of a formal MTP using high plasma and platelet ratios resulted in a substantial increase in abdominal wall approximation. This occurred concurrently to a decrease in the delivered volume of crystalloid fluid.

  2. Mutational analysis of the cell cycle inhibitor Kip1/p27 in childhood leukemia.

    Science.gov (United States)

    Markaki, E-A; Stiakaki, E; Zafiropoulos, A; Arvanitis, D A; Katzilakis, N; Dimitriou, H; Spandidos, D A; Kalmanti, M

    2006-07-01

    Cyclin-dependent kinases (CDKs) and cyclins, their regulatory subunits, govern cell-cycle progression in eukaryotic cells. Kip1/p27 is the main cyclin-dependent kinase inhibitor, which arrests cell division inhibiting G1-S transition. Kip1/p27 seems to play a critical role in the pathogenesis of several human malignancies and its lower expression has been shown to correlate with a poor prognosis in adult solid tumors. Bone marrow blasts from 49 children with leukemia, 37 acute lymphoblastic leukemia (ALL), and 12 acute myeloid leukemia (AML) were studied. Exon 3 of Kip1/p27 was amplified using the polymerase chain reaction technique (PCR). Single strand conformational polymorphism and heterodouplex analysis were performed to detect DNA sequence with altered conformations and were subsequently sequenced to document mutations. Mutations in Kip1/p27 gene were detected in 2 out of 3 T-ALL, 6 out of 12 AML patients, and only 1 out of 34 B lineage ALL cases. Although the patient groups are small, a highly significant relation of the mutation status with the type of leukemia (P = 0.0037) and the risk group according to treatment protocols (P = 0.00021) was estimated. A statistically significant difference in the white blood count was observed (P = 0.019) between the mutated and non-mutated patient groups although no statistically significant association of the mutation status with the hemoglobin and platelets values, karyotype, age, sex, disease progression, and outcome was determined. Based upon these results, the Kip1/p27 mutations should be considered for further prospective testing as an additional parameter for risk stratification and treatment of childhood leukemia. Copyright 2006 Wiley-Liss, Inc.

  3. Masonry fireplace emissions test method: Repeatability and sensitivity to fueling protocol.

    Science.gov (United States)

    Stern, C H; Jaasma, D R; Champion, M R

    1993-03-01

    A test method for masonry fireplaces has been evaluated during testing on six masonry fireplace configurations. The method determines carbon monoxide and particulate matter emission rates (g/h) and factors (g/kg) and does not require weighing of the appliance to determine the timing of fuel loading.The intralaboratory repeatability of the test method has been determined from multiple tests on the six fireplaces. For the tested fireplaces, the ratio of the highest to lowest measured PM rate averaged 1.17 and in no case was greater than 1.32. The data suggest that some of the variation is due to differences in fuel properties.The influence of fueling protocol on emissions has also been studied. A modified fueling protocol, tested in large and small fireplaces, reduced CO and PM emission factors by roughly 40% and reduced CO and PM rates from 0 to 30%. For both of these fireplaces, emission rates were less sensitive to fueling protocol than emission factors.

  4. Posttranscriptional regulation of the karyogamy gene by Kem1p/Xrn1p exoribonuclease and Rok1p RNA helicase of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kim, Jaehee; Jeon, Soonmee; Yang, Yun-Seok; Kim, Jinmi

    2004-01-01

    The major biochemical activities ascribed to Kem1p/Xrn1p of Saccharomyces cerevisiae are 5'-3' exoribonuclease functioning in RNA turnover and a microtubule-binding protein. Mutational analysis has shown that Kem1p/Xrn1p participates in microtubule-related functions such as nuclear fusion (karyogamy) during mating, chromosome transmission, and spindle pole body duplication. Here, evidence is presented that Kem1p plays a specific role in nuclear fusion by affecting, at the posttranscriptional level, the pheromone induction of the karyogamy-specific transcription factor Kar4p and the expression of Rok1p, a putative RNA helicase. We found that Rok1p itself also affects the pheromone induction of Kar4p and thereby participates in nuclear fusion. Analysis of the active-site mutations, xrn1-D206A or D208A, shows that nuclear fusion as well as the Rok1p synthesis do not require the exoribonuclease activity of Kem1p. Our data provide an important insight into the gene-specific regulatory function mediated by the general RNA-modulating enzymes

  5. The effects of sweep numbers per average and protocol type on the accuracy of the p300-based concealed information test.

    Science.gov (United States)

    Dietrich, Ariana B; Hu, Xiaoqing; Rosenfeld, J Peter

    2014-03-01

    In the first of two experiments, we compared the accuracy of the P300 concealed information test protocol as a function of numbers of trials experienced by subjects and ERP averages analyzed by investigators. Contrary to Farwell et al. (Cogn Neurodyn 6(2):115-154, 2012), we found no evidence that 100 trial based averages are more accurate than 66 or 33 trial based averages (all numbers led to accuracies of 84-94 %). There was actually a trend favoring the lowest trial numbers. The second study compared numbers of irrelevant stimuli recalled and recognized in the 3-stimulus protocol versus the complex trial protocol (Rosenfeld in Memory detection: theory and application of the concealed information test, Cambridge University Press, New York, pp 63-89, 2011). Again, in contrast to expectations from Farwell et al. (Cogn Neurodyn 6(2):115-154, 2012), there were no differences between protocols, although there were more irrelevant stimuli recognized than recalled, and irrelevant 4-digit number group stimuli were neither recalled nor recognized as well as irrelevant city name stimuli. We therefore conclude that stimulus processing in the P300-based complex trial protocol-with no more than 33 sweep averages-is adequate to allow accurate detection of concealed information.

  6. Control room envelope unfiltered air inleakage test protocols

    International Nuclear Information System (INIS)

    Lagus, P.L.; Grot, R.A.

    1997-01-01

    In 1983, the Advisory Committee on Reactor Safeguards (ACRS) recommended that the US NRC develop a control room HVAC performance testing protocol. To date no such protocol has been forthcoming. Beginning in mid-1994, an effort was funded by NRC under a Small Business Innovation Research (SBIR) grant to develop several simplified test protocols based on the principles of tracer gas testing in order to measure the total unfiltered inleakage entering a CRE during emergency mode operation of the control room ventilation system. These would allow accurate assessment of unfiltered air inleakage as required in SRP 6.4. The continuing lack of a standard protocol is unfortunate since one of the significant parameters required to calculate operator dose is the amount of unfiltered air inleakage into the control room. Often it is assumed that, if the Control Room Envelope (CRE) is maintained at +1/8 in. w.g. differential pressure relative to the surroundings, no significant unfiltered inleakage can occur it is further assumed that inleakage due to door openings is the only source of unfiltered air. 23 refs., 13 figs., 2 tabs

  7. Control room envelope unfiltered air inleakage test protocols

    Energy Technology Data Exchange (ETDEWEB)

    Lagus, P.L. [Lagus Applied Technology, San Diego, CA (United States); Grot, R.A. [Lagus Applied Technology, Olney, MD (United States)

    1997-08-01

    In 1983, the Advisory Committee on Reactor Safeguards (ACRS) recommended that the US NRC develop a control room HVAC performance testing protocol. To date no such protocol has been forthcoming. Beginning in mid-1994, an effort was funded by NRC under a Small Business Innovation Research (SBIR) grant to develop several simplified test protocols based on the principles of tracer gas testing in order to measure the total unfiltered inleakage entering a CRE during emergency mode operation of the control room ventilation system. These would allow accurate assessment of unfiltered air inleakage as required in SRP 6.4. The continuing lack of a standard protocol is unfortunate since one of the significant parameters required to calculate operator dose is the amount of unfiltered air inleakage into the control room. Often it is assumed that, if the Control Room Envelope (CRE) is maintained at +1/8 in. w.g. differential pressure relative to the surroundings, no significant unfiltered inleakage can occur it is further assumed that inleakage due to door openings is the only source of unfiltered air. 23 refs., 13 figs., 2 tabs.

  8. Intraesophageal administratio (JP4-039) and p53/MDM2/MDM4 Inhibitor (BEB55) ameliorates radiation esophagitisn of GS-Nitroxide

    NARCIS (Netherlands)

    Kim, H.; Bernard, M.; Epperly, M.W.; Shen, H.; Dixon, T.M.; Amoscato, A.A.; Doemling, A.S.; Li, S.; Gao, X.; Wipf, P.

    2011-01-01

    Purpose/Objective(s): To evaluate the esophageal radiation dose modification properties of the GS-nitroxide (JP4-039) and the p53/MDM2/MDM4 inhibitor (BEB55). Materials/Methods: Esophagitis is a significant toxicity of radiation therapy of thoracic cancers. We evaluated radiation dose modification

  9. Understanding protocol performance: impact of test performance.

    Science.gov (United States)

    Turner, Robert G

    2013-01-01

    This is the second of two articles that examine the factors that determine protocol performance. The objective of these articles is to provide a general understanding of protocol performance that can be used to estimate performance, establish limits on performance, decide if a protocol is justified, and ultimately select a protocol. The first article was concerned with protocol criterion and test correlation. It demonstrated the advantages and disadvantages of different criterion when all tests had the same performance. It also examined the impact of increasing test correlation on protocol performance and the characteristics of the different criteria. To examine the impact on protocol performance when individual tests in a protocol have different performance. This is evaluated for different criteria and test correlations. The results of the two articles are combined and summarized. A mathematical model is used to calculate protocol performance for different protocol criteria and test correlations when there are small to large variations in the performance of individual tests in the protocol. The performance of the individual tests that make up a protocol has a significant impact on the performance of the protocol. As expected, the better the performance of the individual tests, the better the performance of the protocol. Many of the characteristics of the different criteria are relatively independent of the variation in the performance of the individual tests. However, increasing test variation degrades some criteria advantages and causes a new disadvantage to appear. This negative impact increases as test variation increases and as more tests are added to the protocol. Best protocol performance is obtained when individual tests are uncorrelated and have the same performance. In general, the greater the variation in the performance of tests in the protocol, the more detrimental this variation is to protocol performance. Since this negative impact is increased as

  10. An interesting charmonium state formation and decay: p p-bar → 1 D2 → 1 P1γ

    International Nuclear Information System (INIS)

    Anselmino, M.; Caruso, F.; Universidade do Estado, Rio de Janeiro, RJ; Murgia, F.; Negrao, M.R.

    1994-01-01

    Massless perturbative QCD forbids, at leading order, the exclusive annihilation of proton-antiproton into some charmonium states, which however, have been observed in the pp channel, indicating the significance of higher order and non perturbative effects in the few GeV energy region. The most well known cases are those of the 1 S 0 (η c ) and the 1 P 1 . The case of the 1 D 2 is considered here and a way of detecting such a state through its typical angular distribution in the radiative decay 1 D 2 -> 1 D 2 -> 1 P 1 γ is suggested. Estimates of the branching ratio BR( 1 D 2 ->pp), as given by a quark-diquark model of the nucleon, mass corrections and an instanton induced process are presented. (author). 15 refs

  11. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-01-01

    Highlights: ► MH7A cells and CD4 + T cells expressed S1P1 and RANKL. ► S1P increased RANKL expression in MH7A cells and CD4 + T cells. ► The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4 + T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4 + T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4 + T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4 + T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4 + T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  12. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  13. Comprehensive behavioral analysis of ENU-induced Disc1-Q31L and -L100P mutant mice

    Directory of Open Access Journals (Sweden)

    Shoji Hirotaka

    2012-02-01

    Full Text Available Abstract Background Disrupted-in-Schizophrenia 1 (DISC1 is considered to be a candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. A recent study reported that N-ethyl-N-nitrosourea (ENU-induced mutations in exon 2 of the mouse Disc1 gene, which resulted in the amino acid exchange of Q31L and L100P, caused an increase in depression-like behavior in 31 L mutant mice and schizophrenia-like behavior in 100P mutant mice; thus, these are potential animal models of psychiatric disorders. However, remaining heterozygous mutations that possibly occur in flanking genes other than Disc1 itself might induce behavioral abnormalities in the mutant mice. Here, to confirm the effects of Disc1-Q31L and Disc1-L100P mutations on behavioral phenotypes and to investigate the behaviors of the mutant mice in more detail, the mutant lines were backcrossed to C57BL/6JJcl through an additional two generations and the behaviors were analyzed using a comprehensive behavioral test battery. Results Contrary to expectations, 31 L mutant mice showed no significant behavioral differences when compared with wild-type control mice in any of the behavioral tests, including the Porsolt forced swim and tail suspension tests, commonly used tests for depression-like behavior. Also, 100P mutant mice exhibited no differences in almost all of the behavioral tests, including the prepulse inhibition test for measuring sensorimotor gating, which is known to be impaired in schizophrenia patients; however, 100P mutant mice showed higher locomotor activity compared with wild-type control mice in the light/dark transition test. Conclusions Although these results are partially consistent with the previous study in that there was hyperactivity in 100P mutant mice, the vast majority of the results are inconsistent with those of the previous study; this discrepancy may be explained by differences in the genetic background of the

  14. Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

    Science.gov (United States)

    Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

    2016-10-01

    Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

    Science.gov (United States)

    Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

    2018-01-01

    Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ototoxic potential of JP-8 and a Fischer-Tropsch synthetic jet fuel following subacute inhalation exposure in rats.

    Science.gov (United States)

    Fechter, Laurence D; Gearhart, Caroline A; Fulton, Sherry

    2010-07-01

    This study was undertaken to identify the ototoxic potential of two jet fuels presented alone and in combination with noise. Rats were exposed via a subacute inhalation paradigm to JP-8 jet fuel, a kerosene-based fuel refined from petroleum, and a synthetic fuel produced by the Fischer-Tropsch (FT) process. Although JP-8 contains small ( approximately 5%) concentrations of aromatic hydrocarbons some of which known to be ototoxic, the synthetic fuel does not. The objectives of this study were to identify a lowest observed adverse effect level and a no observed adverse effect level for each jet fuel and to provide some preliminary, but admittedly, indirect evidence concerning the possible role of the aromatic hydrocarbon component of petroleum-based jet fuel on hearing. Rats (n = 5-19) received inhalation exposure to JP-8 or to FT fuel for 4 h/day on five consecutive days at doses of 500, 1000, and 2000 mg/m(3). Additional groups were exposed to various fuel concentrations followed by 1 h of an octave band of noise, noise alone, or no exposure to fuel or noise. Significant dose-related impairment in the distortion product otoacoustic emissions (DPOAE) was seen in subjects exposed to combined JP-8 plus noise exposure when JP-8 levels of at least 1000 mg/m(3) were presented. No noticeable impairment was observed at JP-8 levels of 500 mg/m(3) + noise. In contrast to the effects of JP-8 on noise-induced hearing loss, FT exposure had no effect by itself or in combination with noise exposure even at the highest exposure level tested. Despite an observed loss in DPOAE amplitude seen only when JP-8 and noise were combined, there was no loss in auditory threshold or increase in hair cell loss in any exposure group.

  17. Results of the Proficiency Test, PT1 and PT2, 2011

    DEFF Research Database (Denmark)

    Kahns, Søren; Nicolajsen, Nicole; Christophersen, Maj-Britt

    2012-01-01

    A comparative test of diagnostic procedures was provided by the EU Reference Laboratory (EURL) for Fish Diseases to 41 National Reference Laboratories (NRLs) in the start of middle of October 2011. The test was prepared and tested according to protocols accredited by DANAK under registration numb...... 515 to proficiency testing according to the quality assurance standard DS/EN ISO/IEC 17043. The test consisted of 2 tests: PT1 and PT2....

  18. Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

    Science.gov (United States)

    Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

    2017-08-01

    Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Protocols to test the activity of antimicrobial peptides against the honey bee pathogen Paenibacillus larvae.

    Science.gov (United States)

    Khilnani, Jasmin C; Wing, Helen J

    2015-10-01

    Paenibacillus larvae is the causal agent of the honey bee disease American Foulbrood. Two enhanced protocols that allow the activity of antimicrobial peptides to be tested against P. larvae are presented. Proof of principle experiments demonstrate that the honey bee antimicrobial peptide defensin 1 is active in both assays. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Thermochemical properties of exo-tricyclo[5.2.1.0(2,6)]decane (JP-10 jet fuel) and derived tricyclodecyl radicals.

    Science.gov (United States)

    Hudzik, Jason M; Asatryan, Rubik; Bozzelli, Joseph W

    2010-09-09

    exo-Tricyclo[5.2.1.0(2,6)]decane (TCD) or exo-tetrahydrodicyclopentadiene is the principal component of the high-energy density hydrocarbon fuel commonly identified as JP-10. Thermodynamic parameters for the parent TCD molecule and of all the tricyclodecyl radicals corresponding to the loss of hydrogen atoms from different carbons sites (TCD-Ri with i indicating the given carbon center) are determined using several density functional theory and G3MP2B3 and CBS-QB3 higher level composite computational chemistry methods. Five isodesmic work reactions, three involving bridged hydrocarbon reference molecules with similar ring strains, are employed to produce a cancelation of systematic calculation errors in evaluation of standard, gas-phase formation enthalpies at 298 K. Delta(f)H degrees (298) for TCD is found to be -19.5 +/- 1.3 kcal mol(-1), which is several kcal mol(-1) lower than the commonly used values. C(i)-H bond energies for corresponding TCD carbon sites are evaluated as follows: TCD-R1, 107.2; TCD-R2, 100.1; TCD-R3, 98.0; TCD-R4, 98.5; TCD-R9, 98.7; TCD-R10, 104.1 kcal mol(-1). Results from use of five different DFT methods are in very good agreement with composite level values for all work reactions used for the radicals. The exo and endo isomers of TCD are both determined to have chair and boat conformers.

  1. 75 FR 3251 - JP Morgan Chase and Company; JP Morgan Investment Banking, Global Corporate Financial Operations...

    Science.gov (United States)

    2010-01-20

    ... Company; JP Morgan Investment Banking, Global Corporate Financial Operations, New York, NY; Notice of... Company, JP Morgan Investment Banking, Global Corporate Financial Operations, New York, New York. The... support operations to/from a foreign country. The subject firm did not import services like or directly...

  2. Resilience to audiogenic seizures is associated with p-ERK1/2 dephosphorylation in the subiculum of Fmr1 knockout mice

    Directory of Open Access Journals (Sweden)

    Giulia eCuria

    2013-04-01

    Full Text Available Young, but not adult, Fmr1 knockout (KO mice display audiogenic seizures (AGS that can be prevented by inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation. In order to identify the cerebral regions involved in these phenomena, we characterized the response to AGS in Fmr1 KO mice and wild type (WT controls at postnatal day (P 45 and P90. To characterize the diverse response to AGS in various cerebral regions, we evaluated the activity markers FosB/ΔFosB and phosphorylated ERK1/2 (p-ERK1/2. Wild running (100% of tested mice followed by clonic/tonic seizures (30% were observed in P45 Fmr1 KO mice, but not in WT mice. In P90 Fmr1 KO mice, wild running was only present in 25% of tested animals. Basal FosB/ΔFosB immunoreactivity was higher (P<0.01 vs WT in the CA1 and subiculum of P45 Fmr1 KO mice. Following the AGS test, FosB/ΔFosB expression consistently increased in most of the analyzed regions in both groups at P45, but not at P90. Interestingly, FosB/ΔFosB immunoreactivity was significantly higher in P45 Fmr1 KO mice in the medial geniculate body (P<0.05 vs WT and CA3 (P<0.01. Neurons presenting with immunopositivity to p-ERK1/2 were more abundant in the subiculum of Fmr1 KO mice in control condition (P<0.05 vs WT, in both age groups. In this region, p-ERK1/2-immunopositive cells significantly decreased (-75%, P<0.01 in P90 Fmr1 KO mice exposed to the AGS test, but no changes were found in P45 mice or in other brain regions. In both age groups of WT mice, p-ERK1/2-immunopositive cells increased in the subiculum after exposure to the acoustic test. Our findings illustrate that FosB/ΔFosB markers are overexpressed in the medial geniculate body and CA3 in Fmr1 KO mice experiencing AGS, and that p-ERK1/2 is markedly decreased in the subiculum of Fmr1 KO mice resistant to AGS induction. These findings suggest that resilience to AGS is associated with dephosphorylation of p-ERK1/2 in the subiculum of mature Fmr1 KO mice.

  3. Role of sphingosine 1-phosphate (S1P and effects of fingolimod, an S1P receptor 1 functional antagonist in lymphocyte circulation and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Kenji Chiba

    2014-11-01

    Full Text Available Sphingosine 1-phosphate (S1P, a multi-functional phospholipid mediator, is generated from sphingosine by sphingosine kinases and binds to five known G protein-coupled S1P receptors (S1P1, S1P2, S1P3, S1P4, and S1P5. It is widely accepted that S1P receptor 1 (S1P1 plays an essential role in lymphocyte egress from the secondary lymphoid organs (SLO and thymus, because lymphocyte egress from these organs to periphery is at extremely low levels in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active S1P1 functional antagonist which was discovered by chemical modification of a natural product, myriocin. Since FTY720 has a structure closely related to sphingosine, the phosphorylated FTY720 (FTY720-P is converted by sphingosine kinases and binds 4 types of S1P receptors. FTY720-P strongly induces down-regulation of S1P1 by internalization and degradation of this receptor and acts as a functional antagonist at S1P1. Consequently, FTY720 inhibits S1P1-dependent lymphocyte egress from the SLO and thymus to reduce circulating lymphocytes including autoreactive Th17 cells, and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. In relapsing remitting MS patients, oral FTY720 shows a superior efficacy when compared to intramuscular interferon-β-1a. Based on these data, it is presumed that modulation of the S1P-S1P1 axis provides an effective therapy for autoimmune diseases including MS.

  4. Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation.

    Science.gov (United States)

    Wang, S; Young, R S; Witten, M L

    2001-02-01

    Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.

  5. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    Science.gov (United States)

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  6. Developing a dynamic virtual stimulation protocol to induce linear egomotion during orthostatic posture control test

    Directory of Open Access Journals (Sweden)

    Paulo José Guimarães Da-Silva

    Full Text Available Abstract Introduction In this work, the effect of a dynamic visual stimulation (DS protocol was used to induce egomotion, the center of pressure (COP displacement response. Methods DS was developed concerning the scenario structure (chessboard-pattern floor and furniture and luminance. To move the scenario in a discrete forward (or backward direction, the furniture is expanded (or reduced and the black and white background is reversed during floor translation while the luminance is increased (or reduced by steps of 2 cd/m2. This protocol was evaluated using COP signals from 29 healthy volunteers: standing on a force platform observing the virtual scene (1.72 × 1.16 m projected 1 m ahead (visual incidence angle: θl = 81.4° and θv = 60.2°, which moves with constant velocity (2 m/s during 250 ms. A set of 100 DS was applied in random order, interspersed by a 10 s of static scene. Results The Tukey post-hoc test (p < 0.001 indicated egomotion in the same direction of DS. COP displacement increased over stimulation (8.4 ± 1.7 to 22.6 ±5.3 mm, as well as time to recover stability (4.1 ± 0.4 to 7.2 ± 0.6 s. The peak of egomotion during DSF occurred 200 ms after DSB (Wilcoxon, p = 0.002. Conclusion The dynamic configuration of this protocol establishes virtual flow effects of linear egomotion dependent on the direction of the dynamic visual stimulation. This finding indicates the potential application of the proposed virtual dynamic stimulation protocol to investigate the cortical visual evoked response in postural control studies.

  7. Test Specification of A1-1 Test for OECD-ATLAS Project

    International Nuclear Information System (INIS)

    Kang, Kyoung-Ho; Moon, Sang-Ki; Lee, Seung-Wook; Choi, Ki-Yong; Song, Chul-Hwa

    2014-01-01

    In the OECD-ATLAS project, design extension conditions (DECs) such as a station blackout (SBO) and a total loss of feed water (TLOFW) will be experimentally investigated to meet the international interests in the multiple high-risk DECs raised after the Fukushima accident. The proposed test matrix for the OECD-ATLAS project is summarized in Table 1.. In this study, detailed specification of the first test named as A1-1 in the OECD-ATLAS project was described. The target scenario of the A1-1 test is a prolonged SBO with delayed supply of turbine-driven auxiliary feedwater to only SG number 2 (SG-2). A SBO is one of the most important DECs in that without any proper operator actions, a total loss of heat sink leads to core uncover, to core damage, and ultimately a core melt-down scenario under high pressure. Due to this safety importance, a SBO is considered to be a base test item of the OECD-ATLAS project. A detailed specification of the first test named as A1-1 in the OECD-ATLAS project was described. The target scenario of the A1-1 test is a prolonged SBO with delayed supply of turbine-driven auxiliary feedwater to only SG-2 in order to consider an accident mitigation measure. The pre-test analysis using MARS code was performed with an aim of setting up the detailed test procedures for A1-1 test and also gaining the physical insights for a prolonged SBO transient. In the A1-1 test, a prolonged SBO transient will be simulated with two temporal phases: Phase (I) for conservative SBO transient without supply of turbine-driven auxiliary feedwater and Phase (II) for asymmetric cooling via single trained supply of turbine-driven auxiliary feedwater

  8. Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Stefan Bittner

    2015-07-01

    Full Text Available Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5 channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K2P5.1 knockout (K2P5.1−/− mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K2P5.1−/− mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs.

  9. Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors.

    Science.gov (United States)

    Callihan, Phillip; Alqinyah, Mohammed; Hooks, Shelley B

    2018-01-01

    Sphingosine-1-phosphate (S1P) and its receptors are important in nervous system development. Reliable in vitro human model systems are needed to further define specific roles for S1P signaling in neural development. We have described S1P-regulated signaling, survival, and differentiation in a human embryonic stem cell-derived neuroepithelial progenitor cell line (hNP1) that expresses functional S1P receptors. These cells can be further differentiated to a neuronal cell type and therefore represent a good model system to study the role of S1P signaling in human neural development. The following sections describe in detail the culture and differentiation of hNP1 cells and two assays to measure S1P signaling in these cells.

  10. Test-retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943

    International Nuclear Information System (INIS)

    Saricicek, Aybala; Chen, Jason; Ruf, Barbara; Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun; Subramanyam, Kalyani; Maloney, Kathleen; Matuskey, David; Deserno, Lorenz; Neumeister, Alexander; Krystal, John H.; Carson, Richard E.; Bhagwagar, Zubin

    2015-01-01

    [ 11 C]P943 is a novel, highly selective 5-HT 1B PET radioligand. The aim of this study was to determine the test-retest reliability of [ 11 C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP ND was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP ND , 0.5 % and 11.5 % for MA1 BP P , 16.7 % and 28.3 % for MA1 BP F , and between 0.2 % and 5.4 % for MRTM2 BP ND . The power analyses showed a greater number of subjects were required using MA1 BP F compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP ND and the lowest with MA1 BP F in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT 1B receptor binding can be obtained using the novel PET radioligand [ 11 C]P943. Quantification of 5-HT 1B receptor binding with MRTM2 BP ND and with MA1 BP P provided the least variability and optimal power for within-subject and

  11. Familial partial duplication (1)(p21p31)

    Energy Technology Data Exchange (ETDEWEB)

    Hoechstetter, L.; Soukup, S.; Schorry, E.K. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)

    1995-11-20

    A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30-year-old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed. 8 refs., 5 figs., 1 tab.

  12. Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis.

    Science.gov (United States)

    Yang, Le; Yue, Shi; Yang, Lin; Liu, Xin; Han, Zhen; Zhang, Yuanyuan; Li, Liying

    2013-07-01

    Sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) axis is involved in multiple biological processes, including liver fibrosis. Angiogenesis is an important pathophysiological process closely associated with liver fibrosis; however, the functional role of SphK/S1P/S1PR in this process remains incompletely defined. Bile duct ligation or carbon tetrachloride was used to induce liver fibrosis in mice. Human fibrotic samples were obtained from livers of patients undergoing liver transplantation. S1P levels in the liver were examined by HPLC. Expression of angiogenic markers, including angiopoietin 1, CD31, vascular cell adhesion molecule-1, and von Willebrand factor, was characterized by immunofluorescence, real-time RT-PCR, and Western blot in the fibrotic liver and primary mouse hepatic stellate cells (HSCs). SphK inhibitor (SKI) or S1PR antagonists were administered intraperitoneally in mice. S1P levels in the liver were closely correlated with mRNA expression of angiogenic markers. Ang1 is expressed in activated HSCs of the fibrotic liver and in primary HSCs. In HSCs, by using specific antagonists or siRNAs, we demonstrated S1P stimulation induced Ang1 expression via S1PR1 and S1PR3. In vivo, S1P reduction by SKI inhibited angiogenesis in fibrotic mice. Furthermore, S1PR1/3 antagonist significantly blocked upregulation of angiogenic markers in the injured liver, and attenuated the extent of liver fibrosis, while S1PR2 antagonist had no effect on angiogenesis, supporting the key role of S1PR1 and S1PR3 in angiogenesis underlying liver fibrosis process. SphK1/S1P/S1PR1/3 axis plays a crucial role in the angiogenic process required for fibrosis development, which may represent an effective therapeutic strategy for liver fibrosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. HIV-1 integrase inhibitors are substrates for the multidrug transporter MDR1-P-glycoprotein

    Directory of Open Access Journals (Sweden)

    Cara Andrea

    2007-03-01

    Full Text Available Abstract Background The discovery of diketoacid-containing derivatives as inhibitors of HIV-1 Integrase (IN (IN inhibitors, IINs has played a major role in validating this enzyme as an important target for antiretroviral therapy. Since the in vivo efficacy depends on access of these drugs to intracellular sites where HIV-1 replicates, we determined whether the IINs are recognized by the multidrug transporter MDR1-P-glycoprotein (P-gp thereby reducing their intracellular accumulation. To address the effect of IINs on drug transport, nine quinolonyl diketo acid (DKA derivatives active on the HIV-1 IN strand transfer (ST step and with EC50 ranging from 1.83 to >50 μm in cell-based assays were tested for their in vitro interaction with P-gp in the CEM-MDR cell system. IINs were investigated for the inhibition and induction of the P-gp function and expression as well as for multidrug resistance (MDR reversing ability. Results The HIV-1 IINs act as genuine P-gp substrates by inhibiting doxorubicin efflux and inducing P-gp functional conformation changes as evaluated by the modulation of UIC2 mAb epitope. Further, IINs chemosensitize MDR cells to vinblastine and induce P-gp expression in drug sensitive revertants of CEM-MDR cells. Conclusion To our knowledge, this is the first demonstration that HIV-1 IINs are P-gp substrates. This biological property may influence the absorption, distribution and elimination of these novels anti HIV-1 compounds.

  14. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    Science.gov (United States)

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  15. Independent validation testing of the FLAME computer code, Version 1.0

    International Nuclear Information System (INIS)

    Martian, P.; Chung, J.N.

    1992-07-01

    Independent testing of the FLAME computer code, Version 1.0, was conducted to determine if the code is ready for use in hydrological and environmental studies at Department of Energy sites. This report describes the technical basis, approach, and results of this testing. Validation tests, (i.e., tests which compare field data to the computer generated solutions) were used to determine the operational status of the FLAME computer code and were done on a qualitative basis through graphical comparisons of the experimental and numerical data. These tests were specifically designed to check: (1) correctness of the FORTRAN coding, (2) computational accuracy, and (3) suitability to simulating actual hydrologic conditions. This testing was performed using a structured evaluation protocol which consisted of: (1) independent applications, and (2) graduated difficulty of test cases. Three tests ranging in complexity from simple one-dimensional steady-state flow field problems under near-saturated conditions to two-dimensional transient flow problems with very dry initial conditions

  16. PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

    Science.gov (United States)

    Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2013-11-01

    We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

  17. Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

    Science.gov (United States)

    Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

    2013-01-01

    Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

  18. Inhalation Exposure to Jet Fuel (JP8) Among U.S. Air Force Personnel

    Science.gov (United States)

    2010-10-01

    are occupationally exposcd.(I) )nfonnation on the health consequences o f human exposure 10 JP8 is limited.(I·2) though there is some evidence that...JP8 may be toxic to the immune system. respirdtory trdCt, and nervous system at exposure concentrations ncar 350 mg/m·1.m The current ACG lH...Egeghy et al.(7) and to reflect a scheme that may be used in epidemiologic studies assessing exposure and hcalth outcomes . The high exposure group

  19. ARPA-NRL Laser Program - Semiannual Technical Report to Defense Advanced Research Projects Agency, 1 January 1974-30 June 1974

    Science.gov (United States)

    1975-04-01

    Johnson and R.G, Fijw!’r, I. Chem. I’hys P. Millet , i. Salamero, n. Brunei, J. Goly, Ü. Bl.inc, and J, L. fuysslri...Chem Phys. 53, 1004 (1970). i «. wnem. ’Reference 4. ’P. Millet , Y. Salamero, H. Brunei, ,1. Galv. D. Blanc and J.L. reysster, J, Chem...1973) . 7. N. Djeu and R. Burnham, to be published. 8. P. Jean , M. Martin, J.P. Barrat, and J.L. Cojan, Compt. Rend. 264B, 609 (1967). 9. J.P

  20. Evidence suggesting superiority of visual (verbal) vs. auditory test presentation modality in the P300-based, Complex Trial Protocol for concealed autobiographical memory detection.

    Science.gov (United States)

    Rosenfeld, J Peter; Ward, Anne; Frigo, Vincent; Drapekin, Jesse; Labkovsky, Elena

    2015-04-01

    One group of participants received a series of city name stimuli presented on trials of the Complex Trial Protocol (CTP) version of a P300-based, concealed information test (CIT). Stimuli were presented on alternating trials in either auditory or visual presentation modality. In 1/7 of the trials the participant's home town (probe) repeatedly appeared in a series of 6 other (irrelevant) repeated city names. In both modalities, probe stimuli produced larger P300s than irrelevant stimuli. Visual stimuli produced shorter behavioral reaction times and P300 latencies, as well as larger P300 probe amplitudes, probe-irrelevant amplitude differences, and individual diagnostic accuracies than the same stimuli presented in the auditory modality. Possible reasons for these effects are discussed, and subject to discussed limitations, the applied conclusion reached is that in all CITs, visual presentation of stimuli, if feasible, should be preferentially used. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Observation of the 1P1 state of charmonium

    International Nuclear Information System (INIS)

    Armstrong, T.A.; Bettoni, D.; Bharadwaj, V.; Biino, C.; Borreani, G.; Broemmelsiek, D.; Buzzo, A.; Calabrese, R.; Ceccucci, A.; Cester, R.; Church, M.; Dalpiaz, P.; Dalpiaz, P.F.; Dibenedetto, R.; Dimitroyannis, D.; Fabbri, M.G.; Fast, J.; Gianoli, A.; Ginsburg, C.M.; Gollwitzer, K.; Hahn, A.; Hasan, M.; Hsueh, S.; Lewis, R.; Luppi, E.; Macri, M.; Majewska, A.M.; Mandelkern, M.; Marchetto, F.; Marinelli, M.; Marques, J.; Marsh, W.; Martini, M.; Masuzawa, M.; Menichetti, E.; Migliori, A.; Mussa, R.; Palestini, S.; Pallavicini, M.; Pastrone, N.; Patrignani, C.; Peoples, J. Jr.; Pesando, L.; Petrucci, F.; Pia, M.G.; Pordes, S.; Rapidis, P.; Ray, R.; Reid, J.; Rinaudo, G.; Roccuzzo, B.; Rosen, J.; Santroni, A.; Sarmiento, M.; Savrie, M.; Scalisi, A.; Schultz, J.; Seth, K.K.; Smith, A.; Smith, G.A.; Sozzi, M.; Trokenheim, S.; Weber, M.F.; Werkema, S.; Zhang, Y.; Zhao, J.; Zioulas, G.

    1992-01-01

    We have performed a search for the 1 P 1 state of charmonium resonantly formed in bar pp annihilations, close to the center of gravity of the 3 P J states. We report results from the study of the J/ψ+π 0 and J/ψ+2π final states. We have observed a statistically significant enhancement in the bar p+p→J/ψ+π 0 cross section at √s congruent 3526.2 MeV. This enhancement has the characteristics of a narrow resonance of mass, total width, and production cross section consistent with what is expected for the 1 P 1 state. In our search we have found no candidates for the reactions bar p+p→J/ψ+π 0 +π 0 and bar p+p→J/ψ+π + +π -

  2. Summary report on parametric pressure propagation test T0127-1

    International Nuclear Information System (INIS)

    Fauske, H.K.

    1993-06-01

    This report presents the results of two ferrocyanide propagating reaction generated aerosol tests, conducted as a part of a series of tests directed by Westinghouse Hanford Company (WHC). The tests discussed in this document are designated as T0208-1 and T0209-1. The tests were carried out in a 49 L containment volume equipped with an aerosol filter housing. The test setup is described in Section 2.0. Each test used an ∼ 50 gm. sample of InFarm-1 bottom flow sheet material which was vacuum dried, screened through a 140 mesh sieve, and rehydrated to 1 wgt. % water content prior to testing. The test sample and reaction ignition method are described in Section 3.0. A special test protocol was defined and followed for the tests as described in Section 4.0 and Appendix B. Test results are discussed in Section 5.0. Both tests yielded a significant aerosol sample on the filter element. These filter elements and aerosol deposits have been sent to WHC for analysis, and any information as to the content or chemical composition of the trapped particulate material awaits the results of WHC efforts in this regard. The reaction propagation tests were conducted at 60 degrees C and 120 degrees C respectively. The average propagation velocities are consistent with other related observations

  3. Sphingosine 1-Phosphate (S1P) Carrier-dependent Regulation of Endothelial Barrier

    Science.gov (United States)

    Wilkerson, Brent A.; Grass, G. Daniel; Wing, Shane B.; Argraves, W. Scott; Argraves, Kelley M.

    2012-01-01

    Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function. PMID:23135269

  4. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

    KAUST Repository

    Chatel, Benjamin; Bendahan, David; Hourdé , Christophe; Pellerin, Luc; Lengacher, Sylvain; Magistretti, Pierre J.; Le Fur, Yann; Vilmen, Christophe; Bernard, Monique; Messonnier, Laurent A.

    2017-01-01

    The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

  5. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

    KAUST Repository

    Chatel, Benjamin

    2017-03-03

    The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

  6. Reaction-to-Fire of Wood Products and Other Building Materials: Part 1, Room/Corner Test Performance

    Science.gov (United States)

    Ondrej Grexa; Mark A. Dietenberger; Robert H. White

    2012-01-01

    This project researched the assessment of reaction-to-fire of common materials using the full-scale room/corner test (ISO 9705) protocol and the predictions of time to flashover using results from the bench-scale cone calorimeter test (ISO 5660-1). Using a burner protocol of 100 kW for 10 min, followed by 300 kW for 10 min and the test materials on the walls only, we...

  7. Biochemical and immunological characterization of recombinant allergen Lol p 1.

    Science.gov (United States)

    Tamborini, E; Faccini, S; Lidholm, J; Svensson, M; Brandazza, A; Longhi, R; Groenlund, H; Sidoli, A; Arosio, P

    1997-11-01

    Pollen from perennial rye grass (Lolium perenne), a major cause of type-I allergy worldwide, contains a complex mixture of allergenic proteins among which Lol p 1 is one of the most important. We describe the expression, purification and characterization of a recombinant Lol p 1 overproduced in Escherichia coli. The recombinant allergen, expressed in high yields and purified in milligram amounts, bound to specific IgE antibodies from human sera, induced histamine release from sensitized human basophils, and elicited rabbit antisera that recognize specifically recombinant Lol p 1 and natural Lol p 1 of pollen extract. Recombinant Lol p 1 was used to develop ImmunoCAP assays for analysis of 150 sera that were Radioallergosorbent test positive to L. perenne pollen. In 130 of them (87%) the assay detected a significant level of IgE antibodies to Lol p 1, reaching on average 37% of the level obtained with a test for IgE to the whole grass pollen extract. To map epitopes on Lol p 1, we produced three deletion mutants [des-(116-240)-Lol p 1, des-(1-88)-Lol p 1 and des-(133-189)-Lol p 1], which were efficiently expressed in bacteria. These all showed a strong reactivity with the specific rabbit IgG antibodies, but lacked most or all the allergenic properties of recombinant Lol p 1. A study of the antigenic structure of Lol p 1 was performed using the three deletion mutants and a set of 17-18-residue overlapping synthetic peptides covering the whole allergen sequence. The results indicate that human IgE and rabbit IgG antibodies bind to distinct regions of Lol p 1, and that at least some important IgE epitopes are mainly conformational. The findings suggest that recombinant allergens constitute useful reagents for further development of serological diagnosis of allergy, and that it should be possible to produce immunogenic fragments of allergenic proteins without allergenic properties.

  8. Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Jensen, P H

    1985-01-01

    A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25)....

  9. Test OPTRAN 1-1 results

    International Nuclear Information System (INIS)

    Martinson, Z.R.

    1982-01-01

    The objective of the OPT 1-1 Test Series was to evaluate the extent of damage and the threshold for failure during simulated BWR anticipated transients. Four power transient tests with progressively higher power levels were performed with preirradiated fuel rods at power ramp rates as high as 550 kW/m per second. Six separately shrouded fuel rods fabricated by the General Electric Co., and preirradiated in the Monticello BWR to burnups of about 5000 to 23,000 MWd/t were tested, four at a time. Four of the fuel rods were of typical GE 8 x 8 design, except for fuel length (0.75 m). Two of the rods included design modifications to improve their PCI-resistant characteristics. A lengthy fuel conditioning preceded the transient testing of the fuel rods

  10. 28 August 2013 - Director of Technical Quality Management Head of ESTEC Establishment European Space Agency F. Ongaro visiting the LHC tunnel at Point 1 with Technology Department Head F. Bordry and Technology Department J.-P. Tock; visiting the ATLAS experimental area with ATLAS Deputy Spokesperson T. Wengler and signing the guest book with CERN Director-General R. Heuer. Accompanied throughout by F. Bordry and V. Parma.

    CERN Multimedia

    Jean-Claude Gadmer

    2013-01-01

    28 August 2013 - Director of Technical Quality Management Head of ESTEC Establishment European Space Agency F. Ongaro visiting the LHC tunnel at Point 1 with Technology Department Head F. Bordry and Technology Department J.-P. Tock; visiting the ATLAS experimental area with ATLAS Deputy Spokesperson T. Wengler and signing the guest book with CERN Director-General R. Heuer. Accompanied throughout by F. Bordry and V. Parma.

  11. Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism.

    Science.gov (United States)

    Bigaud, Marc; Dincer, Zuhal; Bollbuck, Birgit; Dawson, Janet; Beckmann, Nicolau; Beerli, Christian; Fishli-Cavelti, Gina; Nahler, Michaela; Angst, Daniela; Janser, Philipp; Otto, Heike; Rosner, Elisabeth; Hersperger, Rene; Bruns, Christian; Quancard, Jean

    2016-01-01

    Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3-4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates.

  12. SIRT1 mediates Sphk1/S1P-induced proliferation and migration of endothelial cells.

    Science.gov (United States)

    Gao, Zhan; Wang, Hua; Xiao, Feng-Jun; Shi, Xue-Feng; Zhang, Yi-Kun; Xu, Qin Qin; Zhang, Xiao-Yan; Ha, Xiao-Qin; Wang, Li-Sheng

    2016-05-01

    Angiogenesis is one of the most important components of embryonic organ formation and vessel growth after birth. Sphingosine kinase 1 (Sphk1) and S1P has been confirmed to participate in various cell signaling pathways and physiological processes including neovascularisation. However, the mechanisms that Sphk1/S1P regulates neovascularisation remain unclear. In this study, we elucidated that Sphk1/S1P upregulates sirtuin 1 (SIRT1), a NAD+ dependent deacetylases protease which exerts multiple cellular functions, to regulate the proliferation and migration of endothelial cells. By using CCK8 and Transwell assays, we demonstrated that Sphk1 and SIRT1 knockdown could significantly decrease proliferation and migration of HUVEC cells. Sphk1 inhibition results in SIRT1 downregulation which could be reversed by exogenous S1P in HUVEC cells. Treatment of HUVECs with S1P reverses the impaired proliferation and migration caused by SIRT1 knockdown. Furthermore, Sphk1 knockdown inhibits the phosphorylation of P38 MAPK, ERK and AKT. Treatment of HUVECs with PD98059, SB203580 and Wortmannin, which are the inhibitors of ERK, P38 MAPK and AKT respectively, resulted in decreased SIRT1 expression and reduced migration of HUVEC cells. Thus, we conclude that Sphk1/S1P induces SIRT1 upregulation through multiple pathways including P38 MAPK, ERK and AKT signals. This is the first report to disclose the existence and roles of Sphk1/S1P/SIRT1 axis in regulation of endothelial cell proliferation and migration, which may provide a theoretical basis for angiogenesis. Copyright © 2016. Published by Elsevier Ltd.

  13. Histone deacetylase 3 represses p15INK4b and p21WAF1/cip1 transcription by interacting with Sp1

    International Nuclear Information System (INIS)

    Huang Weifeng; Tan Dapeng; Wang Xiuli; Han Songyan; Tan Jiang; Zhao Yanmei; Lu Jun; Huang Baiqu

    2006-01-01

    Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cell proliferation. Here we demonstrated that the overexpression of HDAC3 repressed transcription of p15 INK4b and p21 WAF1/cip1 genes in 293T cells, and that the recruitment of HDAC3 to the promoter regions of these genes was critical to this repression. We also showed that HDAC3 repressed GAL4-Sp1 transcriptional activity, and that Sp1 was co-immunoprecipitated with FLAG-tagged HDAC3. We conclude that HDAC3 can repress p15 INK4b and p21 WAF1/cip1 transcription by interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the transcriptional expression of p15 INK4b , but not that of p21 WAF1/cip1 , implicating the different roles of HDAC3 in repression of p15 INK4b and p21 WAF1/cip1 transcription. Data from this study indicate that the inhibition of p15 INK4b and p21 WAF1/cip1 may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis

  14. Comparison of test protocols for standard room/corner tests

    Science.gov (United States)

    R. H. White; M. A. Dietenberger; H. Tran; O. Grexa; L. Richardson; K. Sumathipala; M. Janssens

    1998-01-01

    As part of international efforts to evaluate alternative reaction-to-fire tests, several series of room/comer tests have been conducted. This paper reviews the overall results of related projects in which different test protocols for standard room/corner tests were used. Differences in the test protocols involved two options for the ignition burner scenario and whether...

  15. Technical protocol for laboratory tests of transformation of veterinary medicinal products and biocides in liquid manures. Version 1.0

    Energy Technology Data Exchange (ETDEWEB)

    Kreuzig, Robert [Technische Univ. Braunschweig (Germany). Inst. fuer Oekologische Chemie und Abfallanalytik

    2010-07-15

    The technical protocol under consideration describes a laboratory test method to evaluate the transformation of chemicals in liquid bovine and pig manures under anaerobic conditions and primarily is designed for veterinary medicinal products and biocides. The environmentally relevant entry routes into liquid manures occur via urine and feces of cattle and pigs in stable housings after excretion of veterinary medicinal products as parent compounds or metabolites and after the application of biocides in animal housings. Further entry routes such as solid dung application and direct dung pat deposition by production animals on pasture are not considered by this technical protocol. Thus, this technical protocol focused on the sampling of excrements from cattles and pigs kept in stables and fed under standard nutrition conditions. This approach additionally ensures that excrement samples are operationally free of any contamination by veterinary medicinal products and biocides. After the matrix characterization, reference-manure samples are prepared from the excrement samples by adding tap water to adjust defined dry substance contents typical for bovine or pig manures. This technical protocol comprehends a tiered experimental design in two parts: (a) Sampling of excrements and preparation of reference bovine and pig manures; (b) Testing of anaerobic transformation of chemicals in reference manures.

  16. Heating and Efficiency Comparison of a Fischer-Tropsch (FT) Fuel, JP-8+100, and Blends in a Three-Cup Combustor Sector

    Science.gov (United States)

    Thomas, Anna E.; Shouse, Dale T.; Neuroth, Craig; Lynch, Amy; Frayne, Charles W.; Stutrud, Jeffrey S.; Corporan, Edwin; Hankins, Terry; Saxena, Nikita T.; Hendricks, Robert C.

    2012-01-01

    In order to realize alternative fueling for military and commercial use, the industry has set forth guidelines that must be met by each fuel. These aviation fueling requirements are outlined in MIL-DTL-83133F(2008) or ASTM D 7566-Annex standards and are classified as drop-in fuel replacements. This paper provides combustor performance data for synthetic-paraffinic-kerosene- (SPK-) type (Fisher-Tropsch (FT)) fuel and blends with JP-8+100, relative to JP-8+100 as baseline fueling. Data were taken at various nominal inlet conditions: 75 psia (0.52 MPa) at 500 aF (533 K), 125 psia (0.86 MPa) at 625 aF (603 K), 175 psia (1.21 MPa) at 725 aF (658 K), and 225 psia (1.55 MPa) at 790 aF (694 K). Combustor performance analysis assessments were made for the change in flame temperatures, combustor efficiency, wall temperatures, and exhaust plane temperatures at 3%, 4%, and 5% combustor pressure drop (% P) for fuel:air ratios (F/A) ranging from 0.010 to 0.025. Significant general trends show lower liner temperatures and higher flame and combustor outlet temperatures with increases in FT fueling relative to JP-8+100 fueling. The latter affects both turbine efficiency and blade/vane life. In general, 100% SPK-FT fuel and blends with JP-8+100 produce less particulates and less smoke and have lower thermal impact on combustor hardware.

  17. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

    Science.gov (United States)

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  18. Normalization of cortical thickness measurements across different T1 magnetic resonance imaging protocols by novel W-Score standardization.

    Science.gov (United States)

    Chung, Jinyong; Yoo, Kwangsun; Lee, Peter; Kim, Chan Mi; Roh, Jee Hoon; Park, Ji Eun; Kim, Sang Joon; Seo, Sang Won; Shin, Jeong-Hyeon; Seong, Joon-Kyung; Jeong, Yong

    2017-10-01

    The use of different 3D T1-weighted magnetic resonance (T1 MR) imaging protocols induces image incompatibility across multicenter studies, negating the many advantages of multicenter studies. A few methods have been developed to address this problem, but significant image incompatibility still remains. Thus, we developed a novel and convenient method to improve image compatibility. W-score standardization creates quality reference values by using a healthy group to obtain normalized disease values. We developed a protocol-specific w-score standardization to control the protocol effect, which is applied to each protocol separately. We used three data sets. In dataset 1, brain T1 MR images of normal controls (NC) and patients with Alzheimer's disease (AD) from two centers, acquired with different T1 MR protocols, were used (Protocol 1 and 2, n = 45/group). In dataset 2, data from six subjects, who underwent MRI with two different protocols (Protocol 1 and 2), were used with different repetition times, echo times, and slice thicknesses. In dataset 3, T1 MR images from a large number of healthy normal controls (Protocol 1: n = 148, Protocol 2: n = 343) were collected for w-score standardization. The protocol effect and disease effect on subjects' cortical thickness were analyzed before and after the application of protocol-specific w-score standardization. As expected, different protocols resulted in differing cortical thickness measurements in both NC and AD subjects. Different measurements were obtained for the same subject when imaged with different protocols. Multivariate pattern difference between measurements was observed between the protocols. Classification accuracy between two protocols was nearly 90%. After applying protocol-specific w-score standardization, the differences between the protocols substantially decreased. Most importantly, protocol-specific w-score standardization reduced both univariate and multivariate differences in the images while

  19. Measurement of the $\\chi_b(3P)$ mass and of the relative rate of $\\chi_{b1}(1P)$ and $\\chi_{b2}(1P)$ production

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; van den Brand, Johannes; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Lespinasse, Mickael; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Roa Romero, Diego; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wu, Suzhi; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

    2014-10-14

    The production of $\\chi_b$ mesons in proton-proton collisions is studied using a data sample collected by the LHCb detector, at centre-of-mass energies of $\\sqrt{s}=7$ and $8$ TeV and corresponding to an integrated luminosity of 3.0 fb$^{-1}$. The $\\chi_b$ mesons are identified through their decays to $\\Upsilon(1S)\\gamma$ and $\\Upsilon(2S)\\gamma$ using photons that converted to $e^+e^-$ pairs in the detector. The $\\chi_b(3P)$ meson mass, and the relative prompt production rate of $\\chi_{b1}(1P)$ and $\\chi_{b2}(1P)$ mesons as a function of the $\\Upsilon(1S)$ transverse momentum in the $\\chi_b$ rapidity range 2.0< $y$<4.5, are measured. Assuming a mass splitting between the $\\chi_{b1}(3P)$ and the $\\chi_{b2}(3P)$ states of 10.5 MeV/$c^2$, the mass of the $\\chi_{b1}(3P)$ meson is \\begin{equation*} m(\\chi_{b1}(3P))= 10515.7^{+2.2}_{-3.9}(stat) ^{+1.5}_{-2.1}(syst) MeV/c^2. \\end{equation*}

  20. Sphingosine-1-Phosphate Mediates ICAM-1-Dependent Monocyte Adhesion through p38 MAPK and p42/p44 MAPK-Dependent Akt Activation

    Science.gov (United States)

    Lin, Chih-Chung; Lee, I-Ta; Hsu, Chun-Hao; Hsu, Chih-Kai; Chi, Pei-Ling; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-01-01

    Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Sphingosine-1-phosphate (S1P) has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying S1P-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. The effect of S1P on ICAM-1 expression was determined by Western blot and real-time PCR. The involvement of signaling pathways in these responses was investigated by using the selective pharmacological inhibitors and transfection with siRNAs. S1P markedly induced ICAM-1 expression and monocyte adhesion which were attenuated by pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), PI3K (LY294002), or AP-1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c-Src, EGFR, PDGFR, p38, p42, JNK1, c-Jun, or c-Fos. We observed that S1P-stimulated p42/p44 MAPK and p38 MAPK activation was mediated via a c-Src/EGFR and PDGFR-dependent pathway. S1P caused the c-Src/EGFR/PDGFR complex formation. On the other hand, we demonstrated that S1P induced p42/p44 MAPK and p38 MAPK-dependent Akt activation. In addition, S1P-stimulated JNK1/2 phosphorylation was attenuated by SP600125 or PP1. Finally, S1P enhanced c-Fos mRNA levels and c-Jun phosphorylation. S1P-induced c-Jun activation was reduced by PP1, AG1478, AG1296, U0126, SP600125, SB202190, or LY294002. These results demonstrated that S1P-induced ICAM-1 expression and monocyte adhesion were mediated through S1PR1/3/c-Src/EGFR, PDGFR/p38 MAPK, p42/p44 MAPK/Akt-dependent AP-1 activation. PMID:25734900

  1. The role of sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) in the trafficking of normal and malignant cells

    Science.gov (United States)

    Ratajczak, Mariusz Z.; Suszynska, Malwina; Borkowska, Sylwia; Ratajczak, Janina; Schneider, Gabriela

    2014-01-01

    Introduction A common feature of many types of cells is their responsiveness to chemotactic gradients of factors for which they express the corresponding receptors. The most studied chemoattractants so far are peptide-based growth factors and a family of cytokines endowed with strong chemotactic properties, called chemokines. However, additional evidence has accumulated that, in addition to these peptide-based chemoattractants, an important role in cell migration is played by bioactive lipids. Areas covered Solid evidence has accumulated that two bioactive phosphorylated sphingolipids that are derivatives of sphingolipid metabolism, namely sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are potent chemoattractants for a variety of cells. In this review, we will discuss the effect of these two phosphorylated sphingolipids on the trafficking of normal and malignant cells, and, in particular, we will focus on their role in trafficking of normal hematopoietic stem/progenitor cells. Unlike other mediators, S1P under steady state conditions maintain a steep gradient between interstitial fluid and peripheral blood and lymph across the endothelial barrier, which is important in the egress of cells from bone marrow. Both S1P and C1P may be upregulated in damaged tissues, which may result in reversal of this gradient. Expert opinion S1P and C1P are important regulators of the trafficking of normal and malignant cells, and modification of their biological effects will have important applications in optimizing stem cell mobilization and homing, tissue organ/regeneration, and preventing cancer metastasis. PMID:24188167

  2. Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

    Science.gov (United States)

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

    Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Immune response to Mycoplasma pneumoniae P1 and P116 in patients with atypical pneumonia analyzed by ELISA

    Directory of Open Access Journals (Sweden)

    Birkelund Svend

    2004-02-01

    Full Text Available Abstract Background Serology is often used for the diagnosis of Mycoplasma pneumoniae. It is important to identify specific antigens that can distinguish between the presence or absence of antibodies against M. pneumoniae. The two proteins, P116 and P1, are found to be immunogenic. By using these in ELISA it is possible to identify an immune response against M. pneumoniae in serum samples. Results A recombinant protein derived from the P116 protein and one from the P1 protein were used in two ELISA tests, rP116-ELISA and rP1-ELISA. Human serum samples from patients with atypical pneumonia were tested and compared to the results of the complement fixation test. There was a good agreement between the two tests but the rP1-ELISA showed the best discrimination between positive and negative samples. Conclusion Two ELISA tests based on recombinant proteins have been analysed and compared to the complement fixation test results. The two ELISA tests were found suitable for use in serodiagnostics of M. pneumoniae infections. The use of specific antigens eliminates the risk of cross reaction to an immune response against other bacteria.

  4. Ngobeni and Samie, Afr., J. Infect. Dis. (2017) 11 (2): 1-9 https://doi ...

    African Journals Online (AJOL)

    Renay Ngobeni

    (2017) 11 (2): 1-9 ... was 1% in the same population (de Quadros et al., 2015). ... be 60% and 64% in females and males respectively (Negash et al., 2008). ..... De Quadros, R.M., da Rocha, G.C., Romagna, G., de Oliveira, J.P., Ribeiro, D.M ...

  5. Commercial Building Energy Asset Score Program Overview and Technical Protocol (Version 1.1)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Na; Goel, Supriya; Makhmalbaf, Atefe

    2013-08-09

    The U.S. Department of Energy (DOE) is developing a voluntary national scoring system for commercial buildings to help building owners and managers assess a building’s energy-related systems independent of operations. The goal of the score is to facilitate cost-effective investment in energy efficiency improvements of commercial buildings. The system, known as the Commercial Building Energy Asset Score, will allow building owners and managers to compare their building infrastructure against peers and track building upgrades over time. The system will also help other building stakeholders (e.g., building investors, tenants, financiers, and appraisers) understand the relative efficiency of different buildings in a way that is independent from operations and occupancy. This report outlines the technical protocol used to generate the energy asset score, explains the scoring methodology, and provides additional details regarding the energy asset scoring tool. The alternative methods that were considered prior to developing the current approach are described in the Program Overview and Technical Protocol Version 1.0.

  6. Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

    Science.gov (United States)

    Chao, Yi-Chun E; Kupper, Lawrence L; Serdar, Berrin; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

    2006-02-01

    Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

  7. Proceedings of the GICC-1 valorization colloquium; Actes du colloque de valorisation de GICC-1

    Energy Technology Data Exchange (ETDEWEB)

    Deque, M. [Meteo-France/Centre National de Recherches Meteorologiques, 31 - Toulouse (France); Ambrosi, Ph. [Centre International de Recherche sur l' Environnement et le Developpement (CIRED), 75 - Paris (France); Arrouays, D. [INRA, 45 - Orleans (France); Tulkens, H. [Universite Catholique de Louvain (UCL), Louvain-la-Neuve (Belgium); Ciais, Ph. [CEA Saclay, CNRS LSCE, 91 - Gif-sur-Yvette (France); Seguin, P. [INRA, 84 - Avignon (France); Chevallier, P. [ILEE/IRD 34 - Montpellier (France); Lacaux, J.P. [Medias France, 31 - Toulouse (France); Le Maho, Y. [CNRS, CEPE, 67 - Strasbourg (France); Andre, J.C. [CERFACS, 31 - Toulouse (France)

    2004-07-01

    This document gathers the transparencies of the available presentations given at this colloquium on the impacts of climate change on economy, society, ecosystems and public health: 1 - images of climate changes in France in the 21. century according to CNRM and IPSL scenarios (M. Deque); 2 - climatic risks and public policy (P. Ambrosi); 3 - climatic policy and carbon sequestration by forests and agricultural practices (D. Arrouays); 4 - towards new inventories of net greenhouse gas (direct or indirect) and aerosol emissions (P. Ciais); 5 - impact on hydro-systems (P. Chevallier); 6 - impacts on health (J.P. Lacaux); 6 - climate and health (Y. Le Maho); 7 - synthesis of the colloquium (J.C. Andre). (J.S.)

  8. In situ bioremediation of JP-5 jet fuel

    International Nuclear Information System (INIS)

    Eisman, M.P.; Dorwin, E.; Barnes, D.; Nelson, B.

    1991-01-01

    Fuel leaks and spills of the jet fuel JP-5 at various Naval installations are required by law to be remediated. Use of microorganisms for fuel spill remediation is the focus of this paper, which examines biodegradation of JP-5 by means of CO 2 evolution in batch cultures. In particular, the aerobic biodegradation of fresh and weathered JP-5, along with a representative fuel mix of three pure compounds, is examined. Since microorganisms exist in aqueous environments, the solubility in water of fuels and fuel components is also examined. Other chemical properties of the complex mixture of hydrocarbons in JP-5 may affect bioavailability. This paper will also attempt to relate biodegradation to these properties, particularly water solubility and type of hydrocarbon

  9. Conversion of a micro, glow-ignition, two-stroke engine from nitromethane-methanol blend fuel to military jet propellant (JP-8)

    Science.gov (United States)

    Wiegand, Andrew L.

    The goal of the thesis "Conversion of a Micro, Glow-Ignition, Two-Stroke Engine from Nitromethane-Methanol Blend Fuel to Military Jet Propellant (JP-8)" was to demonstrate the ability to operate a small engine on JP-8 and was completed in two phases. The first phase included choosing, developing a test stand for, and baseline testing a nitromethane-methanol-fueled engine. The chosen engine was an 11.5 cc, glow-ignition, two-stroke engine designed for remote-controlled helicopters. A micro engine test stand was developed to load and motor the engine. Instrumentation specific to the low flow rates and high speeds of the micro engine was developed and used to document engine behavior. The second phase included converting the engine to operate on JP-8, completing JP-8-fueled steady-state testing, and comparing the performance of the JP-8-fueled engine to the nitromethane-methanol-fueled engine. The conversion was accomplished through a novel crankcase heating method; by heating the crankcase for an extended period of time, a flammable fuel-air mixture was generated in the crankcase scavenged engine, which greatly improved starting times. To aid in starting and steady-state operation, yttrium-zirconia impregnated resin (i.e. ceramic coating) was applied to the combustion surfaces. This also improved the starting times of the JP-8-fueled engine and ultimately allowed for a 34-second starting time. Finally, the steady-state data from both the nitromethane-methanol and JP-8-fueled micro engine were compared. The JP-8-fueled engine showed signs of increased engine friction while having higher indicated fuel conversion efficiency and a higher overall system efficiency. The minimal ability of JP-8 to cool the engine via evaporative effects, however, created the necessity of increased cooling air flow. The conclusion reached was that JP-8-fueled micro engines could be viable in application, but not without additional research being conducted on combustion phenomenon and

  10. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Weihua Meng

    2015-10-01

    Full Text Available Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0% than in females (14.7%. This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 with the disorder, indicating the need for further research.

  11. A comprehensive evaluation of the sl1p pipeline for 16S rRNA gene sequencing analysis.

    Science.gov (United States)

    Whelan, Fiona J; Surette, Michael G

    2017-08-14

    Advances in next-generation sequencing technologies have allowed for detailed, molecular-based studies of microbial communities such as the human gut, soil, and ocean waters. Sequencing of the 16S rRNA gene, specific to prokaryotes, using universal PCR primers has become a common approach to studying the composition of these microbiota. However, the bioinformatic processing of the resulting millions of DNA sequences can be challenging, and a standardized protocol would aid in reproducible analyses. The short-read library 16S rRNA gene sequencing pipeline (sl1p, pronounced "slip") was designed with the purpose of mitigating this lack of reproducibility by combining pre-existing tools into a computational pipeline. This pipeline automates the processing of raw 16S rRNA gene sequencing data to create human-readable tables, graphs, and figures to make the collected data more readily accessible. Data generated from mock communities were compared using eight OTU clustering algorithms, two taxon assignment approaches, and three 16S rRNA gene reference databases. While all of these algorithms and options are available to sl1p users, through testing with human-associated mock communities, AbundantOTU+, the RDP Classifier, and the Greengenes 2011 reference database were chosen as sl1p's defaults based on their ability to best represent the known input communities. sl1p promotes reproducible research by providing a comprehensive log file, and reduces the computational knowledge needed by the user to process next-generation sequencing data. sl1p is freely available at https://bitbucket.org/fwhelan/sl1p .

  12. GOLD - MicrobeDB.jp | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available search(/contents-en/) != -1 || url.search(/index-e.html/) != -1 ) { document.getElementById(lang).innerHTML=.../) != -1 ) { url = url.replace(-e.html,.html); document.getElementById(lang).innerHTML=[ Japanese |...en/,/jp/); document.getElementById(lang).innerHTML=[ Japanese | English ]; } else if ( url.search(//contents...//) != -1 ) { url = url.replace(/contents/,/contents-en/); document.getElementById(lang).innerHTML=[ Japanes...e(/contents-en/,/contents/); document.getElementById(lang).innerHTML=[ Japanese | English ]; } else if( url.

  13. Download - MicrobeDB.jp | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available search(/contents-en/) != -1 || url.search(/index-e.html/) != -1 ) { document.getElementById(lang).innerHTML=.../) != -1 ) { url = url.replace(-e.html,.html); document.getElementById(lang).innerHTML=[ Japanese |...en/,/jp/); document.getElementById(lang).innerHTML=[ Japanese | English ]; } else if ( url.search(//contents...//) != -1 ) { url = url.replace(/contents/,/contents-en/); document.getElementById(lang).innerHTML=[ Japanes...e(/contents-en/,/contents/); document.getElementById(lang).innerHTML=[ Japanese | English ]; } else if( url.

  14. Round robin test for define an accurate protocol to measure the pore fluid pH of low-pH cementitious materials

    International Nuclear Information System (INIS)

    Alonso, M.C.; Garcia Calvo, J.L.; Pettersson, S.; Puigdomenech, I.; Cunado, M.A.; Vuorio, M.; Weber, H.; Ueda, H.; Naito, M.; Walker, C.; Takeshi, Y.; Cau Dit Coumes, C.

    2012-01-01

    The present research belongs to an international project where several of the main nuclear waste management agencies have been involved. The main objective is the development of agreed procedures or protocols for measuring the pH value using low-pH cementitious products (LopHC). The Pore Fluid Expression (PFE) has been identified as reference method and Ex-situ Leaching methods (ELS) with two variants (filtering and without filtering the obtained suspension) have been identified as routine methods. Both methodologies are based on the extraction of the pore solution of the concrete before pH determination. The protocols employed were based on a broad literature review and in fitting the more critical parameters, such as the sample size, the carbonation affection, the leaching of cement hydrates during the measurement, etc. Moreover, the routine methods were validated with respect to the pore fluid expression results. It appears that the repeatability of the 3 pH measurement protocols is very good and that the results obtained with both ESL procedures agree well with the results given by the PFE technique in the case of low-pH cementitious materials and are acceptable in the case of cementitious materials with high pore fluid pH values, in that case some corrections considering the Ca content of the solution may be needed

  15. 6th July 2010 - United Kingdom Science and Technology Facilities Council W. Whitehorn signing the guest book with Head of International relations F. Pauss, visiting the Computing Centre with Information Technology Department Head Deputy D. Foster, the LHC superconducting magnet test hall with Technology Department P. Strubin,the Centre Control Centre with Operation Group Leader M. Lamont and the CLIC/CTF3 facility with Project Leader J.-P. Delahaye.

    CERN Multimedia

    Teams : M. Brice, JC Gadmer

    2010-01-01

    6th July 2010 - United Kingdom Science and Technology Facilities Council W. Whitehorn signing the guest book with Head of International relations F. Pauss, visiting the Computing Centre with Information Technology Department Head Deputy D. Foster, the LHC superconducting magnet test hall with Technology Department P. Strubin,the Centre Control Centre with Operation Group Leader M. Lamont and the CLIC/CTF3 facility with Project Leader J.-P. Delahaye.

  16. 27 Febuary 2012 - US DoE Associate Director of Science for High Energy Physics J. Siegrist visiting the LHC superconducting magnet test hall with adviser J.-P. Koutchouk and engineer M. Bajko; in CMS experimental cavern with Spokesperson J. Incadela;in ATLAS experimental cavern with Deputy Spokesperson A. Lankford; in ALICE experimental cavern with Spokesperson P. Giubellino; signing the guest book with Director for Accelerators and Technology S. Myers.

    CERN Multimedia

    Laurent Egli

    2012-01-01

    27 Febuary 2012 - US DoE Associate Director of Science for High Energy Physics J. Siegrist visiting the LHC superconducting magnet test hall with adviser J.-P. Koutchouk and engineer M. Bajko; in CMS experimental cavern with Spokesperson J. Incadela;in ATLAS experimental cavern with Deputy Spokesperson A. Lankford; in ALICE experimental cavern with Spokesperson P. Giubellino; signing the guest book with Director for Accelerators and Technology S. Myers.

  17. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    Science.gov (United States)

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

  18. Effect of a feed/fast protocol on pH in the proximal equine stomach.

    Science.gov (United States)

    Husted, L; Sanchez, L C; Baptiste, K E; Olsen, S N

    2009-09-01

    Risk factors for the development of gastric squamous ulcers include various management procedures, such as intermittent feed deprivation that can occur during weight management regimens or stall and dry lot confinement. To investigate the effect of intermittent feed deprivation relative to continuous feed intake on proximal intragastric pH, specifically in the region of the squamous mucosa of the lesser curvature. In 6 horses, pH electrodes were placed just inside of the oesophageal sphincter in the stomach for each of two 72 h protocols (A and B) in a randomised, cross-over design. Protocol A consisted of 12 h fed, 12 h fasted, 24 h fed and 24 h fasted, in sequence. Protocol B consisted of 72 h fed. During the fed periods of each protocol, horses had ad libitum access to coastal Bermuda hay and were fed sweet feed (1 kg, b.i.d.). Horses had ad libitum access to water at all times. Proximal intragastric pH was significantly lower during protocol A, than during protocol B. However, hourly mean pH was significantly different only during the day and evening hours between protocols. During protocol B, mean proximal pH decreased significantly from 03.00 to 09.00 compared to 19.00 to 23.00 h. A moderate positive correlation of hay intake vs. proximal gastric pH could be established. Intermittent feed deprivation decreased proximal gastric pH in horses relative to those horses for which feed was not restricted. However, the effect was only significant when fasting occurred during the day and evening hours, as a nocturnal decrease in pH occurred simultaneously in the fed horses. Episodes of daytime feed deprivation should be avoided if possible, as proximal gastric acid exposure rapidly increases during such events.

  19. Closed expressions for $\\int_{0}^{1} t^{-1} log^{n-1}t log^{p}(1 - t) dt$

    CERN Document Server

    Kölbig, Kurt Siegfried

    1982-01-01

    Closed expressions for the integral integral /sub 0//sup 1/ t/sup -1/ log/sup n-1/t log/sup p/(1-t)dt, whose general form is given elsewhere, are listed for n=1(1)9, p=1(1)9. A formula is derived which allows an easy evaluation of these expressions by formula manipulation on a computer. The majority of the above expressions are given in a microfiche supplement to the paper.

  20. Comparison of subareolar injection lymphoscintigraphy with the 1-day and the 2-day protocols for the detection of sentinel lymph nodes in patients with breast cancer

    International Nuclear Information System (INIS)

    Seok, Ju-Won; Kim, In-Ju; Heo, Young-Jun; Yang, You-Jung; Choi, Yoo-Shin; Kim, Beom-Gyu; Park, Seoug-Jun

    2009-01-01

    Lymphoscintigraphy and sentinel node biopsy are used for the detection of axillary lymph node metastasis in breast cancer patients. However, currently there is no standardized technique. For the detection of axillary lymph node metastasis by lymphoscintigraphy and sentinel node biopsy, in patients with breast cancer, we compared the results of subareolar injections administered on the day of surgery (1-day protocol) with injections administered on the day before surgery (2-day protocol). This study included 412 breast cancer patients who underwent surgery between 2001 and 2004. For the 1-day protocol (1 h before surgery) 0.8 ml of Tc-99m Tin-Colloid (37 MBq) was injected in 203 in the subareolar region on the morning of the surgery. For the 2-day protocol (16 h before surgery) 0.8 ml of Tc-99m Tin-Colloid (185 MBq) was injected in 209 patients on the afternoon before surgery. Lymphoscintigraphy was performed in the supine position and sentinel node identification was performed by hand-held gamma probe during surgery. Among 203 patients with the 1-day protocol, 185 cases (91.1%) were identified by sentinel node lymphoscintigraphy, and 182 cases (89.7%) were identified by gamma probe. Among the 209 patients, in the 2-day protocol, 189 cases (90.4%) had the sentinel node identified by lymphoscintigraphy, and 182 cases (87.1%) by the gamma probe. There was no significant difference in the identification rate of the sentinel node between the 1-day and 2-day protocols by lymphoscintigraphy and the gamma probe (p>0.05, p>0.05). The results of the identification of the sentinel node by subareolar injection according to 1-day or 2-day protocol, in breast cancer patients, showed no significant differences. Because the 2-day protocol allows for an adequate amount of time to perform the lymphoscintigraphy, it is a more useful protocol for the identification of sentinel nodes in patients with breast cancer. (author)

  1. The impact of nonpolar lipids on the regulation of the steryl ester hydrolases Tgl1p and Yeh1p in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Klein, Isabella; Korber, Martina; Athenstaedt, Karin; Daum, Günther

    2017-12-01

    In the yeast Saccharomyces cerevisiae degradation of steryl esters is catalyzed by the steryl ester hydrolases Tgl1p, Yeh1p and Yeh2p. The two steryl ester hydrolases Tgl1p and Yeh1p localize to lipid droplets, a cell compartment storing steryl esters and triacylglycerols. In the present study we investigated regulatory aspects of these two hydrolytic enzymes, namely the gene expression level, protein amount, stability and enzyme activity of Tgl1p and Yeh1p in strains lacking both or only one of the two major nonpolar lipids, steryl esters and triacylglycerols. In a strain lacking both nonpolar lipids and consequently lipid droplets, Tgl1p as well as Yeh1p were present at low amount, became highly unstable compared to wild-type cells, and lost their enzymatic activity. Under these conditions both steryl ester hydrolases were retained in the endoplasmic reticulum. The lack of steryl esters alone was not sufficient to cause an altered intracellular localization of Tgl1p and Yeh1p. Surprisingly, the stability of Tgl1p and Yeh1p was markedly reduced in a strain lacking triacylglycerols, but their capacity to mobilize steryl esters remained unaffected. We also tested a possible cross-regulation of Tgl1p and Yeh1p by analyzing the behavior of each hydrolase in the absence of its counterpart steryl ester hydrolases. In summary, this study demonstrates a strong regulation of the two lipid droplet associated steryl ester hydrolases Tgl1p and Yeh1p due to the presence/absence of their host organelle. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Comparative electrophysiological evaluation of hippocampal function following repeated inhalation exposures to JP-8, Jet A, JP-5, and the synthetic Fischer Tropsch fuel.

    Science.gov (United States)

    Rohan, Joyce G; McInturf, Shawn M; Miklasevich, Molly K; Gut, Chester P; Grimm, Michael D; Reboulet, James E; Howard, William R; Mumy, Karen L

    2018-01-01

    Exposure to fuels continues to be a concern in both military and general populations. The aim of this study was to examine effects of in vivo rat repeated exposures to different types of jet fuel utilizing microelectrode arrays for comparative electrophysiological (EP) measurements in hippocampal slices. Animals were exposed to increasing concentrations of four jet fuels, Jet Propellant (JP)-8, Jet A, JP-5, or synthetic Fischer Tropsch (FT) fuel via whole-body inhalation for 20 d (6 hr/d, 5 d/week for 28 d) and synaptic transmission as well as behavioral performance were assessed. Our behavioral studies indicated no significant changes in behavioral performance in animals exposed to JP-8, Jet A, or JP-5. A significant deviation in learning pattern during the Morris water maze task was observed in rats exposed to the highest concentration of FT (2000 mg/m 3 ). There were also significant differences in the EP profile of hippocampal neurons from animals exposed to JP-8, Jet A, JP-5, or FT compared to control air. However, these differences were not consistent across fuels or dose dependent. As expected, patterns of EP alterations in brain slices from JP-8 and Jet A exposures were more similar compared to those from JP-5 and FT. Further longitudinal investigations are needed to determine if these EP effects are transient or persistent. Such studies may dictate if and how one may use EP measurements to indicate potential susceptibility to neurological impairments, particularly those that result from inhalation exposure to chemicals or mixtures.

  3. SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

    Science.gov (United States)

    Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

    2015-03-01

    Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

  4. ASSESSMENT OF RIP-V1 AND OSPF-V2 PROTOCOL WITH CONSIDERATION OF CONVERGENCE CRITERIA AND SENDING PROTOCOLS TRAFFIC

    Directory of Open Access Journals (Sweden)

    Hamed Jelodar

    2014-03-01

    Full Text Available Routing Protocols are underlying principles in networks like internet, transport and mobile. Routing Protocols include a series of rules and algorithms that consider routing metric and select the best way for sending healthy data packets from origin to destination. Dynamic routing protocol compatible to topology has a changeable state. RIP and OSPF are dynamic routing protocol that we consider criteria like convergence and sending protocols traffic assessment RIP first version and OSPF second version. By the test we have done on OPNET stimulation we understood that the OSPF protocol was more efficient than RIP protocol.

  5. Cloning and tissue expression of cytochrome P450 1B1 and 1C1 ...

    African Journals Online (AJOL)

    Cytochrome P450 1 (CYP1) is widely used as an indicator of exposure to environmental contaminants. In the study, two full-length complementary DNAs encode for CYP1B1 and CYP1C1 were cloned from medaka liver exposed to 500 ppb β-naphthoflavone for 24 h. CYP1B1, having 1984 bp, contains an open reading ...

  6. CP determination and tests for CP or P violation by the V1V2 decay mode

    International Nuclear Information System (INIS)

    Nelson, C.A.

    1984-01-01

    A decay mode such as phiphi, UPSILONUPSILON, K/sup asterisk+/K/sup asterisk-/, or D/sup asterisk+/D/sup asterisk-/ can be used to distinguish between a neutral spin-0 technipion and a neutral spin-0 Higgs particle. By this generalization of phiphi parity test, the CP eigenvalue γ/sub C/P can be determined for an X particle of any spin J which decays CP invariantly into VV, or VV-bar, where each vector meson either decays into two spin-0 bosons, or is ω. The absence in a VV, or VV-bar, decay channel of sin2phi and sinphi terms in the azimuthal distribution is due to CP invariance and/or P invariance. For a V 1 V 2 decay channel without a V 1 bold-arrow-left-rightV 2 exchange property, and in a mode like K/sup asterisk+/K /sup asterisk0/, such terms would imply that P is violated. For a V 1 V 2 mode such as phiω where each vector meson is its own antiparticle, such terms would imply that both P and CP are violated; when CP invariance holds, the γ/sub C/P(-)/sup J/ eigenvalue of X can be determined provided certain amplitudes do not accidentally vanish

  7. Test-retest reliability of a balance testing protocol with external perturbations in young healthy adults.

    Science.gov (United States)

    Robbins, Shawn M; Caplan, Ryan M; Aponte, Daniel I; St-Onge, Nancy

    2017-10-01

    External perturbations are utilized to challenge balance and mimic realistic balance threats in patient populations. The reliability of such protocols has not been established. The purpose was to examine test-retest reliability of balance testing with external perturbations. Healthy adults (n=34; mean age 23 years) underwent balance testing over two visits. Participants completed ten balance conditions in which the following parameters were combined: perturbation or non-perturbation, single or double leg, and eyes open or closed. Three trials were collected for each condition. Data were collected on a force plate and external perturbations were applied by translating the plate. Force plate center of pressure (CoP) data were summarized using 13 different CoP measures. Test-retest reliability was examined using intraclass correlation coefficients (ICC) and Bland-Altman plots. CoP measures of total speed and excursion in both anterior-posterior and medial-lateral directions generally had acceptable ICC values for perturbation conditions (ICC=0.46 to 0.87); however, many other CoP measures (e.g. range, area of ellipse) had unacceptable test-retest reliability (ICCbalance testing protocols that include external perturbations should be made to improve test-retest reliability and diminish learning including more extensive participant training and increasing the number of trials. CoP measures that consider all data points (e.g. total speed) are more reliable than those that only consider a few data points. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Assessment of protocols in cone beam CT with symmetric and asymmetric beam using effective dose and P{sub ka}

    Energy Technology Data Exchange (ETDEWEB)

    Batista, W. O.; Linhares de O, M. V. [Instituto Federal da Bahia, Rua Emidio dos Santos s/n, Barbalho, Salvador, 40301015 Bahia (Brazil); Soares, M. R.; Maia, A. F. [Universidade Federal de Sergipe, Departamento de Fisica, Cidade Universitaria Prof. Jose Aloisio de Campos, Marechal Rondon s/n, Jardim Rosa Elze, 49-100000 Sao Cristovao, Sergipe (Brazil); Caldas, L. V. E., E-mail: wilsonottobatista@gmail.com [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The cone beam CT is an emerging technology in dental radiology with significant differences the point of view of design technology between the various manufacturers on the world market. This study aims to evaluate and compare protocols with similar purposes in a cone beam CT scanner using TLDs and air kerma - area product (P{sub ka}) as kerma index. Measurements were performed on two protocols used to obtain the image the maxilla-mandible in equipment Gendex GXCB 500: Protocol [GX1] extended diameter and asymmetric beam (14 cm x 8.5 cm - maxilla / mandible) and protocol [GX2] symmetrical beam (8.5 cm x 8.5 cm - maxillary / mandible). Was used LiF dosimeters (TLD 100) inserted into a female anthropomorphic phantom manufactured by Radiology Support Devices. For all protocols evaluated the value of P{sub ka} using a meter Diamentor E2 and PTW system Radcal Rapidose. The results obtained for Effective Dose / P{sub ka} these measurements were separated by protocol image. Protocol [GX1]: 44.5 μSv/478 mGy cm{sup 2}; protocol [GX2]: 54.8 μSv/507 mGy cm{sup 2}. These values indicate that the relationship between the diameter of the image acquired in the protocol [GX1] and the diameter of the image in the protocol [GX2] is equal to 1.65, the Effective Dose for the first protocol has lower value at 18%. P{sub ka} values reveal very similar results between the two protocols, although, common sense leads to the interpretation that imaging protocols with field of view (Fov) of large diameters imply high values of effective dose when compared to small diameters. However, in this particular case, this is not true due to the asymmetrical beam technology. Conclude that for the cases where the scanner uses asymmetric beam to obtain images with large diameters that cover the entire face there are advantages from the point of view of reducing the exposure of patients with respect to the use of symmetrical beam and / or to Fov images with a smaller diameter. (Author)

  9. Hemoglobin A1c (HbA1c) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/hemoglobina1chba1ctest.html Hemoglobin A1c (HbA1c) Test To use the sharing features on this page, please enable JavaScript. What is a hemoglobin A1c (HbA1c) test? A hemoglobin A1c (HbA1c) test measures ...

  10. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    Science.gov (United States)

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Autoignition and Combustion of Diesel and JP-8

    National Research Council Canada - National Science Library

    Seshadri, Kalyanasundaram

    2007-01-01

    ...: JP-8, commercial jet fuel (with additive package), or commercial jet fuel (without additives)." The objective of the proposed research is to understand those key aspects of combustion of JP-8 that are required to facilitate this conversion...

  12. RAC1 P29S regulates PD-L1 expression in melanoma

    Science.gov (United States)

    Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

    2015-01-01

    Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

  13. Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss

    Directory of Open Access Journals (Sweden)

    Fuller Gregory N

    2005-09-01

    Full Text Available Abstract Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73, DNA Fragmentation Factor subunits alpha (DFFA and beta (DFFB, and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 (TNFRSF9, TNFRSF25. We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development.

  14. PIE on Safety-Tested AGR-1 Compact 5-1-1

    Energy Technology Data Exchange (ETDEWEB)

    Hunn, John D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Morris, Robert Noel [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Baldwin, Charles A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Montgomery, Fred C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gerczak, Tyler J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-08-01

    Post-irradiation examination (PIE) is being performed in support of tristructural isotropic (TRISO) coated particle fuel development and qualification for High-Temperature Gas-cooled Reactors (HTGRs). AGR-1 was the first in a series of TRISO fuel irradiation experiments initiated in 2006 under the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program; this work continues to be funded by the Department of Energy's Office of Nuclear Energy as part of the Advanced Reactor Technologies (ART) initiative. AGR-1 fuel compacts were fabricated at Oak Ridge National Laboratory (ORNL) in 2006 and irradiated for three years in the Idaho National Laboratory (INL) Advanced Test Reactor (ATR) to demonstrate and evaluate fuel performance under HTGR irradiation conditions. PIE is being performed at INL and ORNL to study how the fuel behaved during irradiation, and to examine fuel performance during exposure to elevated temperatures at or above temperatures that could occur during a depressurized conduction cooldown event. This report summarizes safety testing of irradiated AGR-1 Compact 5-1-1 in the ORNL Core Conduction Cooldown Test Facility (CCCTF) and post-safety testing PIE.

  15. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

    Science.gov (United States)

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-01

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. PMID:26645686

  16. A PET/MRI study towards finding the optimal ["1"8F]Fluciclovine PET protocol for detection and characterisation of primary prostate cancer

    International Nuclear Information System (INIS)

    Elschot, Mattijs; Sandsmark, Elise; Tessem, May-Britt; Selnaes, Kirsten M.; Bathen, Tone F.; Krueger-Stokke, Brage; Stoerkersen, Oeystein; Moestue, Siver A.; Bertilsson, Helena

    2017-01-01

    ["1"8F]Fluciclovine PET imaging shows promise for the assessment of prostate cancer. The purpose of this PET/MRI study is to optimise the PET imaging protocol for detection and characterisation of primary prostate cancer, by quantitative evaluation of the dynamic uptake of ["1"8F]Fluciclovine in cancerous and benign tissue. Patients diagnosed with high-risk primary prostate cancer underwent an integrated ["1"8F]Fluciclovine PET/MRI exam before robot-assisted radical prostatectomy with extended pelvic lymph node dissection. Volumes-of-interest (VOIs) of selected organs (prostate, bladder, blood pool) and sub-glandular prostate structures (tumour, benign prostatic hyperplasia (BPH), inflammation, healthy tissue) were delineated on T2-weighted MR images, using whole-mount histology samples as a reference. Three candidate windows for optimal PET imaging were identified based on the dynamic curves of the mean and maximum standardised uptake value (SUV_m_e_a_n and SUV_m_a_x, respectively). The statistical significance of differences in SUV between VOIs were analysed using Wilcoxon rank sum tests (p<0.05, adjusted for multiple testing). Twenty-eight (28) patients [median (range) age: 66 (55-72) years] were included. An early (W1: 5-10 minutes post-injection) and two late candidate windows (W2: 18-23; W3: 33-38 minutes post-injection) were selected. Late compared with early imaging was better able to distinguish between malignant and benign tissue [W3, SUV_m_e_a_n: tumour vs. BPH 2.5 vs. 2.0 (p<0.001), tumour vs. inflammation 2.5 vs. 1.7 (p<0.001), tumour vs. healthy tissue 2.5 vs. 2.0 (p<0.001); W1, SUV_m_e_a_n: tumour vs. BPH 3.1 vs. 3.1 (p=0.771), tumour vs inflammation 3.1 vs. 2.2 (p=0.021), tumour vs. healthy tissue 3.1 vs. 2.5 (p<0.001)] as well as between high-grade and low/intermediate-grade tumours (W3, SUV_m_e_a_n: 2.6 vs. 2.1 (p=0.040); W1, SUV_m_e_a_n: 3.1 vs. 2.8 (p=0.173)). These differences were relevant to the peripheral zone, but not the central gland

  17. Test-retest reliability of the novel 5-HT{sub 1B} receptor PET radioligand [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Saricicek, Aybala [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Izmir Katip Celebi University, Department of Psychiatry, Izmir (Turkey); Chen, Jason; Ruf, Barbara [Yale University, Department of Psychiatry, New Haven, CT (United States); Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun [Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Subramanyam, Kalyani; Maloney, Kathleen [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Matuskey, David [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Deserno, Lorenz [Charite - Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin (Germany); Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Berlin (Germany); Neumeister, Alexander [Yale University, Department of Psychiatry, New Haven, CT (United States); Mount Sinai School of Medicine, Department of Psychiatry, New York, NY (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Krystal, John H. [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Carson, Richard E. [Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bhagwagar, Zubin [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bristol-Myers Squibb, Wallingford, CT (United States)

    2014-11-27

    [{sup 11}C]P943 is a novel, highly selective 5-HT{sub 1B} PET radioligand. The aim of this study was to determine the test-retest reliability of [{sup 11}C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP{sub ND} was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP{sub ND}, 0.5 % and 11.5 % for MA1 BP{sub P}, 16.7 % and 28.3 % for MA1 BP{sub F}, and between 0.2 % and 5.4 % for MRTM2 BP{sub ND}. The power analyses showed a greater number of subjects were required using MA1 BP{sub F} compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP{sub ND} and the lowest with MA1 BP{sub F} in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT{sub 1B} receptor binding can be obtained using the novel PET radioligand [{sup 11}C]P943. Quantification of 5-HT{sub 1B} receptor binding with MRTM2 BP{sub ND} and with MA1 BP{sub P

  18. Interference phenomena in the JP = 1/2- wave in η photoproduction

    International Nuclear Information System (INIS)

    Anisovich, A.V.; Nikonov, V.A.; Sarantsev, A.V.; Klempt, E.; Thoma, U.; Krusche, B.; Werthmueller, D.

    2015-01-01

    The recent precise experimental results for the photoproduction of η-mesons off the neutron measured with the Crystal Ball/TAPS calorimeter at the MAMI accelerator have been investigated in detail in the framework of the Bonn-Gatchina coupled-channel model. The main result is that the narrow structure observed in the excitation function of γη → nη can be reproduced fully with a particular interference pattern in the J P = 1/2 - partial wave. Introduction of the narrow resonance N(1685) with the properties reported in earlier publications deteriorates the quality of the fit. (orig.)

  19. Stability of the JP2 clone of Aggregatibacter actinomycetemcomitans.

    Science.gov (United States)

    Haubek, D; Ennibi, O-K; Vaeth, M; Poulsen, S; Poulsen, K

    2009-09-01

    The JP2 clone of Aggregatibacter actinomycetemcomitans is strongly associated with aggressive periodontitis. To obtain information about colonization dynamics of the JP2 clone, we used PCR to examine its presence in 365 Moroccan juveniles from whom periodontal plaque samples were collected at baseline and after one and two years. Periodontal attachment loss was measured at baseline and at the two-year follow-up. At baseline, 43 (12%) carriers of the JP2 clone were found. Nearly half (44 %) of these were persistently colonized with the clone. The relative risk for the development of aggressive periodontitis, adjusted for the concomitant presence of other genotypes of A. actinomycetemcomitans, was highest for individuals continuously infected by the JP2 clone (RR = 13.9; 95% CI, 9.0 to 21.4), indicating a relationship between infectious dose and disease, which further substantiates the evidence for the JP2 clone as a causal factor in aggressive periodontitis.

  20. Mcm1p binding sites in ARG1 positively regulate Gcn4p binding and SWI/SNF recruitment

    OpenAIRE

    Yoon, Sungpil; Hinnebusch, Alan G.

    2009-01-01

    Transcription of the arginine biosynthetic gene ARG1 is activated by Gcn4p, a transcription factor induced by starvation for any amino acid. Previously we showed that Gcn4p binding stimulates the recruitment of Mcm1p and co-activator SWI/SNF to ARG1 in cells via Gcn4p induction through amino acid starvation. Here we report that Gcn4p binding is reduced by point mutations of the Mcm1p binding site and increased by overexpression of Mcm1p. This result suggests that Mcm1p plays a positive role i...

  1. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

    Science.gov (United States)

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-29

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis

    International Nuclear Information System (INIS)

    Kobayashi, Shinta; Tanaka, Atsushi; Fujiki, Yukio

    2007-01-01

    Dynamin-like protein 1 (DLP1) and Pex11pβ function in morphogenesis of peroxisomes. In the present work, we investigated whether Fis1 is involved in fission of peroxisomes. Endogenous Fis1 was morphologically detected in peroxisomes as well as mitochondria in wild-type CHO-K1 and DLP1-defective ZP121 cells. Subcellular fractionation studies also revealed the presence of Fis1 in peroxisomes. Peroxisomal Fis1 showed the same topology, i.e., C-tail anchored membrane protein, as the mitochondrial one. Furthermore, ectopic expression of FIS1 induced peroxisome proliferation in CHO-K1 cells, while the interference of FIS1 RNA resulted in tubulation of peroxisomes, hence reducing the number of peroxisomes. Fis1 interacted with Pex11pβ, by direct binding apparently involving the C-terminal region of Pex11pβ in the interaction. Pex11pβ also interacted with each other, whereas the binding of Pex11pβ to DLP1 was not detectable. Moreover, ternary complexes comprising Fis1, Pex11pβ, and DLP1 were detected by chemical cross-linking. We also showed that the highly conserved N-terminal domain of Pex11pβ was required for the homo-oligomerization of Pex11pβ and indispensable for the peroxisome-proliferating activity. Taken together, these findings indicate that Fis1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with Pex11pβ and DLP1

  3. Assessment of epicutaneous testing of a monovalent Influenza A (H1N1 2009 vaccine in egg allergic patients

    Directory of Open Access Journals (Sweden)

    Pitt Tracy

    2011-02-01

    Full Text Available Abstract Background H1N1 is responsible for the first influenza pandemic in 41 years. In the fall of 2009, an H1N1 vaccine became available in Canada with the hopes of reducing the overall effect of the pandemic. The purpose of this study was to assess the safety of administering 2 different doses of a monovalent split virus 2009 H1N1 vaccine in egg allergic patients. Methods Patients were skin tested to the H1N1 vaccine in the outpatient paediatric and adult allergy and immunology clinics of the Health Sciences Centre and Children's Hospital of Winnipeg, Manitoba Canada. Individuals Results A total of 61 patients with egg allergy (history of an allergic reaction to egg with either positive skin test &/or specific IgE to egg >0.35 Ku/L were referred to our allergy clinics for skin testing to the H1N1 vaccine. 2 patients were excluded, one did not have a skin prick test to the H1N1 vaccine (only vaccine administration and the other passed an egg challenge during the study period. Ages ranged from 1 to 27 years (mean 5.6 years. There were 41(69.5% males and 18(30.5% females. All but one patient with a history of egg allergy, positive skin test to egg and/or elevated specific IgE level to egg had negative skin tests to the H1N1 vaccine. The 58 patients with negative skin testing to the H1N1 vaccine were administered the vaccine and observed for 30 minutes post vaccination with no adverse results. The patient with the positive skin test to the H1N1 vaccine was also administered the vaccine intramuscularly with no adverse results. Conclusions Despite concern regarding possible anaphylaxis to the H1N1 vaccine in egg allergic patients, in our case series 1/59(1.7% patients with sensitization to egg were also sensitized to the H1N1 vaccine. Administration of the H1N1 vaccine in egg allergic patients with negative H1N1 skin tests and observation is safe. Administering the vaccine in a 1 or 2 dose protocol without skin testing is a reasonable alternative

  4. Astrophysical s-factor measurements for {sup 1}20Te(p,{gamma}){sup 1}21I and {sup 1}20Te(p,n){sup 1}20I reactions; {sup 1}20Te(p,{gamma}){sup 1}21I ve {sup 1}20Te(p,n){sup 1}20I reaksiyonlarinin astrofiziksel s-factor oelcuemleri

    Energy Technology Data Exchange (ETDEWEB)

    Gueray, R T; Oezkan, N; Yalcin, C [Kocaeli University, Kocaeli (Turkey); Goerres, J; DeBoer, R; Palumbo, A; Tan, W P; Wiescher, M [University of Notre Dame, (United States); Fueloep, Zs; Somorjai, E [Institute of Nuclear Research ATOMKI (Hungary); Lee, H Y [Argonne National Laboratory (United States)

    2009-07-01

    Astrophysical S-factors for the {sup 1}20Te(p,{gamma}){sup 1}21I and {sup 1}20Te(p,n){sup 1}20I reactions have been measured in the effective center-of-mass energies between 2.47 MeV and 7.93 MeV. Experimental data have been compared with the Hauser-Fesbach statistical model calculations obtained with the model codes NON-SMOKER and TALYS. The discrepancies between the experimental results and calculations can mainly be attributed to the optical model potentials used in the codes.

  5. Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in patients with T1 bladder tumours: clinical implications and prognostic significance.

    Science.gov (United States)

    Blanca Pedregosa, A M; Sánchez-González, Á; Carrasco Valiente, J; Ruiz García, J M; Gómez Gómez, E; López Beltrán, A; Requena Tapia, M J

    2017-04-01

    To determine the differential protein expression of biomarkers FGFR3, PI3K (subunits PI3Kp110α, PI3KClassIII, PI3Kp85), AKT, p21Waf1/Cip1 and cyclins D1 and D3 in T1 bladder cancer versus healthy tissue and to study their potential role as early recurrence markers. This is a prospective study that employed a total of 67 tissue samples (55 cases of T1 bladder tumours that underwent transurethral resection and 12 cases of adjacent healthy mucosa). The protein expression levels were assessed using Western blot, and the means and percentages were compared using Student's t-test and the chi-squared test. The survival analysis was conducted using the Kaplan-Meier method and the log-rank test. Greater protein expression was detected for FGFR3, PI3Kp110α, PI3KClassIII, cyclins D1 and D3 and p21Waf1/Cip1 in the tumour tissue than in the healthy mucosa. However, these differences were not significant for PI3Kp85 and AKT. We observed statistically significant correlations between early recurrence and PI3Kp110α, PI3KClassIII, PI3Kp85 and AKT (P=.003, P=.045, P=.050 and P=.028, respectively), between the tumour type (primary vs. recurrence) and cyclin D3 (P=.001), between the tumour size and FGFR3 (P=.035) and between multifocality and cyclin D1 (P=.039). The survival analysis selected FGFR3 (P=.024), PI3Kp110α (P=.014), PI3KClassIII (P=.042) and AKT (P=.008) as markers of early-recurrence-free survival. There is an increase in protein expression levels in bladder tumour tissue. The overexpression of FGFR3, PI3Kp110α, PI3KClassIII and AKT is associated with increased early-recurrence-free survival for patients with T1 bladder tumours. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. The sphingosine 1-phosphate receptor S1P(2) triggers hepatic wound healing

    NARCIS (Netherlands)

    Serriere-Lanneau, Valerie; Teixeira-Clerc, Fatima; Li, Liying; Schippers, Marlies; de Wries, Willie; Julien, Boris; Tran-Van-Nhieu, Jeanne; Manin, Sylvie; Poelstra, Klaas; Chun, Jerold; Carpentier, Stephane; Levade, Thierry; Mallat, Ariane; Lotersztajn, Sophie

    Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P(1), S1P(2), and S1P(3)) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here

  7. Sp1/3 and NF-1 mediate basal transcription of the human P2X1 gene in megakaryoblastic MEG-01 cells

    Directory of Open Access Journals (Sweden)

    Ennion Steven J

    2006-03-01

    Full Text Available Abstract Background P2X1 receptors play an important role in platelet function as they can induce shape change, granule centralization and are also involved in thrombus formation. As platelets have no nuclei, the level of P2X1 expression depends on transcriptional regulation in megakaryocytes, the platelet precursor cell. Since nothing is known about the molecular mechanisms regulating megakaryocytic P2X1 expression, this study aimed to identify and functionally characterize the P2X1 core promoter utilized in the human megakaryoblastic cell line MEG-01. Results In order to identify cis-acting elements involved in the transcriptional regulation of P2X1 expression, the ability of 4.7 kb P2X1 upstream sequence to drive luciferase reporter gene expression was tested. Low promoter activity was detected in proliferating MEG-01 cells. This activity increased 20-fold after phorbol-12-myristate-13-acetate (PMA induced differentiation. A transcription start site was detected 365 bp upstream of the start codon by primer extension. Deletion analysis of reporter constructs indicated a core promoter located within the region -68 to +149 bp that contained two Sp1 sites (named Sp1a and Sp1b and an NF-1 site. Individual mutations of Sp1b or NF-1 binding sites severely reduced promoter activity whereas triple mutation of Sp1a, Sp1b and NF-1 sites completely abolished promoter activity in both untreated and PMA treated cells. Sp1/3 and NF-1 proteins were shown to bind their respective sites by EMSA and interaction of Sp1/3, NF-1 and TFIIB with the endogenous P2X1 core promoter in MEG-01 cells was demonstrated by chromatin immunoprecipitation. Alignment of P2X1 genes from human, chimp, rat, mouse and dog revealed consensus Sp1a, Sp1b and NF-1 binding sites in equivalent positions thereby demonstrating evolutionary conservation of these functionally important sites. Conclusion This study has identified and characterized the P2X1 promoter utilized in MEG-01 cells and

  8. Test-retest reliability of jump execution variables using mechanography: a comparison of jump protocols.

    Science.gov (United States)

    Fitzgerald, John S; Johnson, LuAnn; Tomkinson, Grant; Stein, Jesse; Roemmich, James N

    2018-05-01

    Mechanography during the vertical jump may enhance screening and determining mechanistic causes underlying physical performance changes. Utility of jump mechanography for evaluation is limited by scant test-retest reliability data on force-time variables. This study examined the test-retest reliability of eight jump execution variables assessed from mechanography. Thirty-two women (mean±SD: age 20.8 ± 1.3 yr) and 16 men (age 22.1 ± 1.9 yr) attended a familiarization session and two testing sessions, all one week apart. Participants performed two variations of the squat jump with squat depth self-selected and controlled using a goniometer to 80º knee flexion. Test-retest reliability was quantified as the systematic error (using effect size between jumps), random error (using coefficients of variation), and test-retest correlations (using intra-class correlation coefficients). Overall, jump execution variables demonstrated acceptable reliability, evidenced by small systematic errors (mean±95%CI: 0.2 ± 0.07), moderate random errors (mean±95%CI: 17.8 ± 3.7%), and very strong test-retest correlations (range: 0.73-0.97). Differences in random errors between controlled and self-selected protocols were negligible (mean±95%CI: 1.3 ± 2.3%). Jump execution variables demonstrated acceptable reliability, with no meaningful differences between the controlled and self-selected jump protocols. To simplify testing, a self-selected jump protocol can be used to assess force-time variables with negligible impact on measurement error.

  9. Analysis of Semiscale Mod-1 integral test with asymmetrical break (Test S-29-1)

    International Nuclear Information System (INIS)

    Langerman, M.A.

    1977-03-01

    Selected experimental data obtained from Semiscale Mod-1 cold leg break Test S-29-1 and results obtained from analytical codes are analyzed. This test was the first integral blowdown reflood test conducted with the Mod-1 system and was a special test designed specifically to evaluate the sensitivity of the early Mod-1 core thermal response (0 to 5 sec after rupture) to the magnitude and direction of the core flow. To achieve this specific objective in Test S-29-1, the vessel side break area was reduced to approximately one-half the scaled break area associated with a 200 percent cold leg break test. The reduction in break area significantly reduced the core flow reversal that took place immediately after rupture and resulted in periods of positive core flow in the early portion of the test. The results obtained from this test are compared with results obtained from a 200 percent cold leg break test and the effect of core flow on early core thermal response is evaluated. Since Test S-29-1 was the first integral blowdown reflood test conducted with the Mod-1 system, data are also presented through the reflood stage of the test and the results are analyzed. The test data and the core thermal response calculated with the RELAP4 code are also compared

  10. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation

    Science.gov (United States)

    Messias, Carolina V.; Santana-Van-Vliet, Eliane; Lemos, Julia P.; Moreira, Otacilio C.; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000–10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

  11. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

    Directory of Open Access Journals (Sweden)

    Carolina V Messias

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5. S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts.

  12. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver.

    Science.gov (United States)

    Ding, Bi-Sen; Liu, Catherine H; Sun, Yue; Chen, Yutian; Swendeman, Steven L; Jung, Bongnam; Chavez, Deebly; Cao, Zhongwei; Christoffersen, Christina; Nielsen, Lars Bo; Schwab, Susan R; Rafii, Shahin; Hla, Timothy

    2016-12-22

    Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 (S1P 1 ) by its natural ligand bound to HDL (HDL-S1P) induces liver regeneration and curtails fibrosis. In mice lacking HDL-S1P, liver regeneration after partial hepatectomy was impeded and associated with aberrant vascular remodeling, thrombosis and peri-sinusoidal fibrosis. Notably, this "maladaptive repair" phenotype was recapitulated in mice that lack S1P 1 in the endothelium. Reciprocally, enhanced plasma levels of HDL-S1P or administration of SEW2871, a pharmacological agonist specific for S1P 1 enhanced regeneration of metabolically functional vasculature and alleviated fibrosis in mouse chronic injury and cholestasis models. This study shows that natural and pharmacological ligands modulate endothelial S1P 1 to stimulate liver regeneration and inhibit fibrosis, suggesting that activation of this pathway may be a novel therapeutic strategy for liver fibrosis.

  13. Toxicological analysis of 1-P-tholiloxi-3-morpholino-2-propanol

    International Nuclear Information System (INIS)

    Rahimov, I.F.; Kimsanov, A.B.; Khaydarov, K.; Kimsanov, B.

    2005-01-01

    We have researched the toxicological analyse of 1-p-tholiloxi-3-morpholino-2-propanol on white rats during the chronic infusion. The influence of, the preparation 1-p-tholiloxi-3-morpholino-2-propanol on exponents, of the whole stable of the existence of tested animals was observed. It obviously shows that during 30 days in 25 and 50 mg/kg doses the masses of the body of the animals didn't show any phenomenon of the organisms, (allergy, anaphylaxis). The mass of a body of the tested and controlled groups of animals in same extent increased. The changes in blood there quite normal

  14. p21(Waf1/Cip1) expression and the p53/MDM2 feedback loop in gastric carcinogenesis

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Offerhaus, G. J.; Meijer, G. A.; Dekker, W.; Kuipers, E. J.; Meuwissen, S. G.

    1999-01-01

    Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a

  15. Enhancement of the response to purinergic agonists in P2Y1 transfected 1321N1 cells by antagonists suramin and PPADS.

    Science.gov (United States)

    Brown, C A; Charlton, S J; Boarder, M R

    1997-03-01

    1. We have previously shown that both suramin and pyridoxal-phosphate-6-azophenyl-2',4' disulphonic acid (PPADS) act as antagonists at transfected P2Y1 receptors. Here we show that under certain experimental conditions these two P2 antagonists can enhance the response to agonists acting at these receptors. 2. The expression of either P2Y1 or P2Y2 receptors in 1321N1 human astrocytoma cells results, on a change of medium, in an elevation of basal (no added agonist) accumulation of [3H]-inositol(poly)phosphates([3H]-InsPx) compared to cells not expressing these receptors. This elevation is much greater in P2Y1 transfectants than in P2Y, transfectants. 3. Both PPADS and suramin reduced this basal level of [3H]-InsPx accumulation in the P2Y1 expressing cells. 4. When a protocol was used which required changing the culture medium, antagonists were added at a concentration which reduced the basal accumulation by about 50%, there was a significant stimulation in response to increasing concentrations of 2-methylthioadenosine 5'-triphosphate (2MeSATP), in the absence of antagonists there was no significant effect of the agonist. 5. However, when 2MeSATP was added in the absence of a change of medium and with no antagonist present, there was a several fold increase in [3H]-InsPx accumulation. These results show that a release of endogenous agonist activity (possibly ATP/ADP) from the P2Y1 expressing cells can create conditions in which a response to an agonist such as 2MeSATP can only be seen in the presence of a competitive antagonist.

  16. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness

    International Nuclear Information System (INIS)

    Young, Nicholas; Van Brocklyn, James R.

    2007-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P 1-5 . S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P 1 , S1P 2 and S1P 3 all contribute positively to S1P-stimulated glioma cell proliferation, with S1P 1 being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P 5 blocks glioma cell proliferation, and inhibits ERK activation. S1P 1 and S1P 3 enhance glioma cell migration and invasion. S1P 2 inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P 2 also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P 2 -stimulated glioma invasion. Thus, while S1P 2 decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix

  17. Association of glutathione S-transferase (GSTM1, T1 and P1 gene polymorphisms with type 2 diabetes mellitus in north Indian population

    Directory of Open Access Journals (Sweden)

    Bid H

    2010-01-01

    Full Text Available Background: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM. The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. Aims: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. Settings and Design: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. Materials and Methods: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP. Statistical Analysis: Fisher′s exact test and χ2 statistics using SPSS software (Version-15.0. Results: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325 and GSTP1 (I/V (P=0.001, OR= 0.397, 95%CI=0.225-0.701 with T2DM and no significant association with GSTT1 (P=0.493. The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496. Conclusions: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V and multiple association in GSTM1 null, T1 present and P1 (I/I, these polymorphisms can be screened in the population to determine the diabetic risk.

  18. E2F-1-Induced p53-independent apoptosis in transgenic mice

    DEFF Research Database (Denmark)

    Holmberg, Christian Henrik; Helin, K.; Sehested, M.

    1998-01-01

    The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl...... involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered...

  19. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    Science.gov (United States)

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Proceedings of the GICC-1 valorization colloquium

    International Nuclear Information System (INIS)

    Deque, M.; Ambrosi, Ph.; Arrouays, D.; Tulkens, H.; Ciais, Ph.; Seguin, P.; Chevallier, P.; Lacaux, J.P.; Le Maho, Y.; Andre, J.C.

    2004-01-01

    This document gathers the transparencies of the available presentations given at this colloquium on the impacts of climate change on economy, society, ecosystems and public health: 1 - images of climate changes in France in the 21. century according to CNRM and IPSL scenarios (M. Deque); 2 - climatic risks and public policy (P. Ambrosi); 3 - climatic policy and carbon sequestration by forests and agricultural practices (D. Arrouays); 4 - towards new inventories of net greenhouse gas (direct or indirect) and aerosol emissions (P. Ciais); 5 - impact on hydro-systems (P. Chevallier); 6 - impacts on health (J.P. Lacaux); 6 - climate and health (Y. Le Maho); 7 - synthesis of the colloquium (J.C. Andre). (J.S.)

  1. A new protocol for extraction of C0t-1 DNA from rice

    African Journals Online (AJOL)

    USER

    2010-07-12

    Jul 12, 2010 ... plant species differentiation and genome evolution. A new protocol to ... According to nick translation theory, the genomic DNA was digested by DNase I and ... according to the formula Cot-1 = 1 = mol/L × Ts. Since highly and.

  2. Mechanical response of FFTF reference and P1 cladding tubes under transient heating

    International Nuclear Information System (INIS)

    Youngahl, C.A.; Ariman, T.; Lepacek, B.E.

    1977-01-01

    Burst tests of Type 316 stainless steel cladding tube samples subjected to increasing temperature and relatively constant internal pressure were conducted to assist in the pretest analysis of the P1 experiment performed in the Sodium Loop Safety Facility. This paper reports and analyzes the burst test results and those of subsequent transient heating work. The use of a modified extensometer in obtaining mechanical response data for stainless steel in the high temperature range is illustrated, some of such data is provided, and the potential of further experiments and analysis is indicated. Tubing of the same design as Fast Flux Test Facility (FFTF) cladding (20% cold worked, 0.230 in. OD, 15 mil wall) was tested as-received and after annealing or electrolytic thinning. P1 tubing (38% cold worked, 0.230 in. OD, 10 mil wall) was tested before and after aging under conditions anticipated in the P1 reactor experiment. The P1 cladding was designed to simulate FFTF tubing that had experienced irradiation embrittlement and attack by cesium oxide and sodium impurities

  3. PreliminaryEquatorial Paleomagnetic results from Mt Kenya lavas. Neil D Opdyke, 1, Dennis V Kent, 2, Kainian Huang ,1, J.P. Patel , 3

    Science.gov (United States)

    Opdyke, N. D.; Kent, D. V.; Huang, K.; Patel, J. P.

    2007-12-01

    Field work on this study was carried out in August of 2006 by field parties from the University of Florida and Rutgers University. Mt Kenya is believed to be Plio-Pleistocene in age and an Argon dating survey is underway Ten samples were taken at each site consisting of one exposure in individual lava Flows. These exposures are usually in road cuts, streambeds and in some cases roadbeds. We sampled 100 sites distributed around the Mt Kenya Massif and to the northeast along the Nyambini range. The equator bisex's Mt Kenya and all sites were sampled within 40" north or south of the equator . The samples were returned to the US and processed at the University of Florida paleomagnetic laboratory. Many sites were severely affected by lightning however after demagnetization 68 sites yielded directions with alpha 95's equal to or less than 10°. Normal magnetized sites dominate, with N=58 (Dec=1°,Inc -0.1°,α95=2.6°) whereas only 10 reverse sites(Dec. =181.9,Inc. .6°α 95=8°) were identified. The combined site mean direction is Dec=1.1°, Inc..= -0.2° and α 95=3.2°. This result is not significantly different from what is expected from the geocentric axial dipole. VGP's were calculated from each site and the dispersion is low with the ASD = 11° which is in agreement with model "G" of MacFadden and McElhinny .No transitional directions were identified . Quadrupole components are not resolved. 1 Department of geological Sciences, the University of Florida , 2 Dept of Geology, Rutgers University,3,dept of Physics ,The University of Nairobi

  4. A Novel and Validated Protocol for Performing MIC Tests to Determine the Susceptibility of Piscirickettsia salmonis Isolates to Florfenicol and Oxytetracycline

    Directory of Open Access Journals (Sweden)

    Sergio Contreras-Lynch

    2017-07-01

    Full Text Available This paper presents a validated protocol, using a novel, specifically formulated medium, to perform broth microdilution antimicrobial susceptibility assays of the salmonid bacterial pathogen Piscirickettsia salmonis. The minimum inhibitory concentrations (MIC for florfenicol and oxytetracycline against 58 P. salmonis isolates recovered from various outbreaks occurred in Chilean salmonid farms were determined using this protocol. Normalized resistance interpretation (NRI analysis was applied to these data to calculate appropriate protocol-specific epidemiological cut-off values. These cut-off values allow the isolates to be categorized as either fully susceptible wild type (WT members of this species, or as manifesting reduced susceptibility non-wild type (NWT. The distribution of MIC values of florfenicol was bimodal and the distribution of the normalized values for the putative WT observation had a standard deviation of 0.896 log2 μg mL-1. This analysis calculated a cut-off value of ≤0.25 μg mL-1 and categorized 33 (56% of the isolates as manifesting reduced susceptibility to florfenicol. For the oxytetracycline MIC data the NRI analysis also treated the distribution as bimodal. The distribution of the normalized values for the putative WT observation had a standard deviation of 0.951 log2 μg mL-1. This analysis gave a cut-off value of ≤0.5 μg mL-1 and categorized five isolates (9% as manifesting reduced susceptibility to oxytetracycline. The susceptibility testing protocol developed in this study was capable of generating MIC data from all the isolates tested. On the basis of the precision of the data it generated, and the degree of separation of values for WT and NWT it achieved, it is argued that this protocol has the performance characteristics necessary for it to be considered as a standard protocol.

  5. The deexcitation of the Ar (3P2, 3p1 and 1P1) states as measured by absorption both in pure argon and in the presence of additives

    International Nuclear Information System (INIS)

    Dutuit, Odile

    1974-01-01

    The de-excitation of the 3 P 2 , 3 p 1 and 1 P 1 states of argon was studied in pure argon between 10 and 200 torr and in Ar + CO and Ar + H 2 mixtures. These states are populated after excitation of the gas by a short (20 ns) pulse of 500 keV electrons (FEBETRON). Under our experimental conditions, the relation between the measured optical density of the lines studied and the concentration of absorbing species was found to be: DO = log I 0 /I ∝ (lC) n with n = 0,4. The three body rate constants k 2 were measured for the two resonant states 3 p 1 (k 2 = (1,65 ± 0,3) x 10 -32 cm 6 s -1 ) and 1 P 1 (k 2 = (1,0 ± 0,2) x 10 -32 cm 6 s -1 ); they had not been considered in previous low pressure studies. For the metastable state 3 P 2 , the measured value of k 2 ((1,6 ± 0,3) x 10 -32 cm 6 s -1 ) is in good agreement with those found in the literature. However, our two body rate constant k 1 is about ten times higher than that found in measurements at low pressure. This difference could be due to a collision-induced emission process at high pressure. The rate constants for the quenching by CO and H 2 were measured for the metastable state 3 P 2 (1,85 and 10,5 x 10 -11 cm 3 s -1 ) and for the resonant states 3 P 1 (4,5 and 20 x 10 -11 cm 3 s -1 ) and 1 P 1 (8,5 and 33 X 10 -11 cm 3 s -1 ). Comparison of the de-excitation cross sections of resonant and metastable states should lead to a better understanding of energy transfer processes from these latter. (author) [fr

  6. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

    Science.gov (United States)

    Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P 1 , S1P 2 , and S1P 3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to G q . We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα 13 but not Gα 12 , Gα q , or Gα i . Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P 3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P 3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P 3 KO mouse heart. CYM-51736, an S1P 3 -specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P 3 receptor- and Gα 13 -mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    Science.gov (United States)

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  8. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase.

    OpenAIRE

    Manns, M P; Griffin, K J; Sullivan, K F; Johnson, E F

    1991-01-01

    LKM-1 autoantibodies, which are associated with autoimmune chronic active hepatitis, recognize P450IID6, a cytochrome P-450 monooxygenase. The reactivities of 26 LKM-1 antisera were tested with a panel of deletion mutants of P450IID6 expressed in Escherichia coli. 22 sera recognize a 33-amino acid segment of P450IID6, and 11 of these recognize a shorter segment, DPAQPPRD. PAQPPR is also found in IE175 of herpes simplex virus type 1 (HSV-1). Antibodies for HSV-1 proteins were detected by ELISA...

  9. Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae*

    Science.gov (United States)

    Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

    2015-01-01

    Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD+ salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. PMID:26276932

  10. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

    Science.gov (United States)

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  11. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Eunjung Moon

    2015-01-01

    Full Text Available Initial and recurrent stroke produces central nervous system (CNS damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  12. Studying protocol-based pain management in the emergency department

    Directory of Open Access Journals (Sweden)

    Akkamahadevi Patil

    2017-01-01

    Full Text Available Background: Majority of the patients presenting to emergency department (ED have pain. ED oligoanalgesia remains a challenge. Aims: This study aims to study the effect of implementing a protocol-based pain management in the ED on (1 time to analgesia and (2 adequacy of analgesia obtained. Settings and Design: Cross-sectional study in the ED. Methods: Patients aged 18–65 years of age with pain of numeric rating scale (NRS ≥4 were included. A series of 100 patients presenting before introduction of the protocol-based pain management were grouped “pre-protocol,” and managed as per existing practice. Following this, a protocol for management of all patients presenting to ED with pain was implemented. Another series of 100 were grouped as “post-protocol” and managed as per the new pain management protocol. The data of patients from both the groups were collected and analyzed. Statistical Analysis Used: Descriptive statistical tests such as percentage, mean and standard deviation and inferential statistical tests such as Pearson coefficient, Student's t-test were applied. Differences were interpreted as significant when P < 0.05. Results: Mean time to administer analgesic was significantly lesser in the postprotocol group (preprotocol 20.30 min vs. postprotocol 13.05 min; P < 0.001. There was significant difference in the pain relief achieved (change in NRS between the two groups, with greater pain relief achieved in the postprotocol group (preprotocol group 4.6800 vs. postprotocol group 5.3600; P < 0.001. Patients' rating of pain relief (assessed on E5 scale was significantly higher in the postprotocol group (preprotocol 3.91 vs. postprotocol 4.27; P = 0.001. Patients' satisfaction (North American Spine Society scale with the overall treatment was also compared and found to be significantly higher in postprotocol group (mean: preprotocol 1.59 vs. postprotocol 1.39; P = 0.008. Conclusion: Protocol-based pain management provided timely and

  13. Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First Large-Scale Protocol to Formally Include Rapid Diagnostic Tests.

    Directory of Open Access Journals (Sweden)

    José Carlos Sousa-Figueiredo

    Full Text Available Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs, there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of 'mapping resolution', as well as present results and treatment recommendations for northern Namibia.This new protocol allowed a large sample to be surveyed (N = 17,896 children from 299 schools at relatively low cost (7 USD per person mapped and very quickly (28 working days. All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001 and defective (OR = 1.2, P<0.001 or absent sanitation infrastructure (OR = 2.0, P<0.001. Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001. Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively performed well, with sensitivities above 80% and specificities above 95%.This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are

  14. Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.

    Science.gov (United States)

    Mahajan-Thakur, Shailaja; Bien-Möller, Sandra; Marx, Sascha; Schroeder, Henry; Rauch, Bernhard H

    2017-11-17

    The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.

  15. Zac1, an Sp1-like protein, regulates human p21WAF1/Cip1 gene expression in HeLa cells

    International Nuclear Information System (INIS)

    Liu, Pei-Yao; Hsieh, Tsai-Yuan; Liu, Shu-Ting; Chang, Yung-Lung; Lin, Wei-Shiang; Wang, Wei-Ming; Huang, Shih-Ming

    2011-01-01

    Zac1 functions as both a transcription factor and a transcriptional cofactor for p53, nuclear receptors (NRs) and NR coactivators. Zac1 might also act as a transcriptional repressor via the recruitment of histone deacetylase 1 (HDAC1). The ability of Zac1 to interact directly with GC-specific elements indicates that Zac1 possibly binds to Sp1-responsive elements. In the present study, our data show that Zac1 is able to interact directly with the Sp1-responsive element in the p21 WAF1/Cip1 gene promoter and enhance the transactivation activity of Sp1 through direct physical interaction. Our data further demonstrate that Zac1 might enhance Sp1-specific promoter activity by interacting with the Sp1-responsive element, affecting the transactivation activity of Sp1 via a protein–protein interaction, or competing the HDAC1 protein away from the pre-existing Sp1/HDAC1 complex. Finally, the synergistic regulation of p21 WAF1/Cip1 gene expression by Zac1 and Sp1 is mediated by endogenous p53 protein and p53-responsive elements in HeLa cells. Our work suggests that Zac1 might serve as an Sp1-like protein that directly interacts with the Sp1-responsive element to oligomerize with and/or to coactivate Sp1.

  16. Experiment data report for semiscale Mod-1 test S-06-1 (LOFT counterpart test)

    International Nuclear Information System (INIS)

    Collins, B.L.; Patton, M.L. Jr.; Sackett, K.E.

    1977-07-01

    Recorded test data are presented for Test S-06-1 of the Semiscale Mod-1 LOFT counterpart test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying an hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-06-1 was conducted from initial conditions of 15 568 kPa and 564 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact loop to simulate emergency core coolant injection in a PWR. The heater rods in the electrically heated core were operated at an axial peak power density which was 30% of the maximum peak power density

  17. Emissions characteristics of Military Helicopter Engines Fueled with JP-8 and a Fischer-Tropsch Fuel

    International Nuclear Information System (INIS)

    Corporan, E.; DeWitt, M.; Klingshirn, Christopher D.; Striebich, Richard; Cheng, Mengdawn

    2010-01-01

    The rapid growth in aviation activities and more stringent U.S. Environmental Protection Agency regulations have increased concerns regarding aircraft emissions, due to their harmful health and environmental impacts, especially in the vicinity of airports and military bases. In this study, the gaseous and particulate-matter emissions of two General Electric T701C engines and one T700 engine were evaluated. The T700 series engines power the U.S. Army's Black Hawk and Apache helicopters. The engines were fueled with standard military JP-8 fuel and were tested at three power settings. In addition, one of the T701C engines was operated on a natural-gas-derived Fischer-Tropsch synthetic paraffinic kerosene jet fuel. Test results show that the T701C engine emits significantly lower particulate-matter emissions than the T700 for all conditions tested. Particulate-matter mass emission indices ranged from 0.2-1.4 g/kg fuel for the T700 and 0.2-0.6 g/kg fuel for the T701C. Slightly higher NOx and lower CO emissions were observed for the T701C compared with the T700. Operation of the T701C with the Fischer-Tropsch fuel rendered dramatic reductions in soot emissions relative to operation on JP-8, due primarily to the lack of aromatic compounds in the alternative fuel. The Fischer-Tropsch fuel also produced smaller particles and slight reductions in CO emissions.

  18. Treatability test plan for the 200-ZP-1 operable unit

    International Nuclear Information System (INIS)

    1994-07-01

    This document presents the treatability test plan for pilot-scale pump and treat testing at the 200-ZP-1 Operable Unit. The approach discussed in this treatability test plan is to conduct a pilot-scale pump and treat test for the contaminant plume associated with the 200-ZP-1 Operable Unit. The primary contaminants of concern are carbon tetrachloride, chloroform, and trichloroethylene (TCE). The pilot-scale treatability testing has as its primary purpose to assess the performance of aboveground treatment systems with respect to the ability to remove the primary contaminants present in groundwater withdrawn from the contaminant plume. The overall scope of this test plan includes: description of the pump and treat system to be tested, as well as the test performance objectives and data quality objectives (DQOs) that will be used to evaluate the effectiveness of the pilot-scale treatment system; discussion of the treatment technology to be tested and supporting development activities, including process flow and conceptual design descriptions and equipment, fabrication, utility, and system startup needs; description of pilot-scale treatment system performance, operating procedures, and operational controls, as well as anticipated monitoring activities, analytes, parameters, analytical procedures, and quality assurance protocols; summaries of other related treatability testing elements, including personnel and environmental health and safety controls, process and secondary waste management and disposition, schedule, and program organization

  19. Vinclozolin: a feasibility and sensitivity study of the ILSI-HESI F1-extended one-generation rat reproduction protocol.

    Science.gov (United States)

    Schneider, Steffen; Kaufmann, Wolfgang; Strauss, Volker; van Ravenzwaay, Bennard

    2011-02-01

    Feasibility of the ILSI-HESI (ACSA) extended one-generation protocol was tested with vinclozolin (dietary 0, 4, 20, 100mg/kg/day). Parental Wistar rats (n=25/sex/dose) were dosed pre-mating (males 4, females 2 weeks) through F1 offspring weaning (postnatal day PND21); F1 dosing continued through PND70. At PND21, 3 subsets (each 1 pup/sex/litter) were selected for neurotoxicology (functional observational battery, motor activity, neuropathology), clinical pathology (hematology, clinical chemistry, urinalysis, thyroid hormone assay) (subsets 1a, 1b; each n=10/sex/dose), immunotoxicology (IgM) SRBC antibody response and natural killer cell assays (subset 2; n=25/sex/dose), and estrus cycle (subset 3; n=25/dose). Vinclozolin reduced parental and offspring bodyweight and prostate, seminal vesicles and epididymides weight, and increased adrenal weight/induced adrenal cortical hypertrophy at 100mg/kg. Mating, fertility, gestation and lactation were unaffected. At 20 and 100mg/kg, F1 males had reduced anogenital distance and retained areolae; at 100mg/kg only, there was hypospadias, purulent prostatitis and seminal vesicle inflammation with atrophy, and Leydig cell hyperplasia, and in F1 females accelerated vaginal opening. These effects are consistent with vinclozolin's known anti-androgenic developmental effects. Neuro- and immunotoxicology tests were unaffected. F1 Only T4 was reduced at 20 and 100mg/kg. The overall sensitivity of the extended one-generation protocol is comparable to or even greater than the current two-generation study. Thus it reduces animal use while maintaining or enhancing information for risk assessment. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. S-Nitrosation destabilizes glutathione transferase P1-1.

    Science.gov (United States)

    Balchin, David; Stoychev, Stoyan H; Dirr, Heini W

    2013-12-23

    Protein S-nitrosation is a post-translational modification that regulates the function of more than 500 human proteins. Despite its apparent physiological significance, S-nitrosation is poorly understood at a molecular level. Here, we investigated the effect of S-nitrosation on the activity, structure, stability, and dynamics of human glutathione transferase P1-1 (GSTP1-1), an important detoxification enzyme ubiquitous in aerobes. S-Nitrosation at Cys47 and Cys101 reduces the activity of the enzyme by 94%. Circular dichroism spectroscopy, acrylamide quenching, and amide hydrogen-deuterium exchange mass spectrometry experiments indicate that the loss of activity is caused by the introduction of local disorder at the active site of GSTP1-1. Furthermore, the modification destabilizes domain 1 of GSTP1-1 against denaturation, smoothing the unfolding energy landscape of the protein and introducing a refolding defect. In contrast, S-nitrosation at Cys101 alone introduces a refolding defect in domain 1 but compensates by stabilizing the domain kinetically. These data elucidate the physical basis for the regulation of GSTP1-1 by S-nitrosation and provide general insight into the consequences of S-nitrosation on protein stability and dynamics.

  1. Vitual screening and binding mode elucidation of curcumin analogues on Cyclooxygenase-2 using AYO_COX2_V1.1 protocol

    Science.gov (United States)

    Mulatsari, E.; Mumpuni, E.; Herfian, A.

    2017-05-01

    Curcumin is yellow colored phenolic compounds contained in Curcuma longa. Curcumin is known to have biological activities as anti-inflammatory, antiviral, antioxidant, and anti-infective agent [1]. Synthesis of curcumin analogue compounds has been done and some of them had biological activity like curcumin. In this research, the virtual screening of curcumin analogue compounds has been conducted. The purpose of this research was to determine the activity of these compounds as selective Cyclooxygenase-2inhibitors in in-silico. Binding mode elucidation was made by active and inactive representative compounds to see the interaction of the amino acids in the binding site of the compounds. This research used AYO_COX2_V.1.1, a structure-based virtual screening protocol (SBVS) that has been validated by Mumpuni E et al, 2014 [2]. AYO_COX2_V.1.1 protocol using a variety of integrated applications such as SPORES, PLANTS, BKchem, OpenBabel and PyMOL. The results of virtual screening conducted on 49 curcumin analogue compounds obtained 8 compounds with 4 active amino acid residues (GLY340, ILE503, PHE343, and PHE367) that were considered active as COX-2 inhibitor.

  2. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

    2017-02-01

    HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

  3. Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae.

    Science.gov (United States)

    Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

    2015-10-16

    Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD(+) salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    Science.gov (United States)

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  5. Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement.

    Science.gov (United States)

    Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo; Zhou, Tingting; Xie, Lishi; Garcia, Joe G N; Jacobson, Jeffrey R

    2014-06-01

    We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI. © 2013 Wiley Periodicals, Inc.

  6. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  7. Wavelengths of the Ni-like 4d1S0 - 4p1P1 x-ray laser line

    International Nuclear Information System (INIS)

    Li, Y.; Nilsen, J.; Dunn, J.; Osterheld, A.L.; Ryabtsev, A.; Churilov, S.

    1998-01-01

    We measure the wavelengths of the Ni-like 3d 9 4d 1 S 0 - 3d 9 4p 1 P 1 x-ray laser line in several low-Z Ni-like ions ranging from Y (Z=39) to Cd (Z=48). These wavelengths are compared with optimized level calculations using a multiconfiguration Dirac-Fock code. With the help of these results, we identify this line to very high accuracy in nonlasing plasmas from As (Z=33) to Mo (Z=42). Accurate values of these wavelengths are essential for performing plasma imaging and interferometry experiments with multilayer optics that use the x-ray laser to backlight other plasmas. These results also provide important atomic data that are currently missing about the energy of the 4d 1 S 0 level in the NiI sequence. copyright 1998 The American Physical Society

  8. Framework and indicator testing protocol for developing and piloting quality indicators for the UK quality and outcomes framework

    Directory of Open Access Journals (Sweden)

    Burke Martyn

    2011-08-01

    Full Text Available Abstract Background Quality measures should be subjected to a testing protocol before being used in practice using key attributes such as acceptability, feasibility and reliability, as well as identifying issues derived from actual implementation and unintended consequences. We describe the methodologies and results of an indicator testing protocol (ITP using data from proposed quality indicators for the United Kingdom Quality and Outcomes Framework (QOF. Methods The indicator testing protocol involved a multi-step and methodological process: 1 The RAND/UCLA Appropriateness Method, to test clarity and necessity, 2 data extraction from patients' medical records, to test technical feasibility and reliability, 3 diaries, to test workload, 4 cost-effectiveness modelling, and 5 semi-structured interviews, to test acceptability, implementation issues and unintended consequences. Testing was conducted in a sample of representative family practices in England. These methods were combined into an overall recommendation for each tested indicator. Results Using an indicator testing protocol as part of piloting was seen as a valuable way of testing potential indicators in 'real world' settings. Pilot 1 (October 2009-March 2010 involved thirteen indicators across six clinical domains and twelve indicators passed the indicator testing protocol. However, the indicator testing protocol identified a number of implementation issues and unintended consequences that can be rectified or removed prior to national roll out. A palliative care indicator is used as an exemplar of the value of piloting using a multiple attribute indicator testing protocol - while technically feasible and reliable, it was unacceptable to practice staff and raised concerns about potentially causing actual patient harm. Conclusions This indicator testing protocol is one example of a protocol that may be useful in assessing potential quality indicators when adapted to specific country health

  9. Quality Assurance Protocol for AFCI Advanced Structural Materials Testing

    Energy Technology Data Exchange (ETDEWEB)

    Busby, Jeremy T [ORNL

    2009-05-01

    The objective of this letter is to inform you of recent progress on the development of advanced structural materials in support of advanced fast reactors and AFCI. As you know, the alloy development effort has been initiated in recent months with the procurement of adequate quantities of the NF616 and HT-UPS alloys. As the test alloys become available in the coming days, mechanical testing, evaluation of optimizing treatments, and screening of environmental effects will be possible at a larger scale. It is therefore important to establish proper quality assurance protocols for this testing effort in a timely manner to ensure high technical quality throughout testing. A properly implemented quality assurance effort will also enable preliminary data taken in this effort to be qualified as NQA-1 during any subsequent licensing discussions for an advanced design or actual prototype. The objective of this report is to describe the quality assurance protocols that will be used for this effort. An essential first step in evaluating quality protocols is assessing the end use of the data. Currently, the advanced structural materials effort is part of a long-range, basic research and development effort and not, as yet, involved in licensing discussions for a specific reactor design. After consultation with Mark Vance (an ORNL QA expert) and based on the recently-issued AFCI QA requirements, the application of NQA-1 quality requirements will follow the guidance provided in Part IV, Subpart 4.2 of the NQA-1 standard (Guidance on Graded Application of QA for Nuclear-Related Research and Development). This guidance mandates the application of sound scientific methodology and a robust peer review process in all phases, allowing for the data to be qualified for use even if the programmatic mission changes to include licensing discussions of a specific design or prototype. ORNL has previously implemented a QA program dedicated to GNEP activities and based on an appropriately graded

  10. Quality Assurance Protocol for AFCI Advanced Structural Materials Testing

    International Nuclear Information System (INIS)

    Busby, Jeremy T.

    2009-01-01

    The objective of this letter is to inform you of recent progress on the development of advanced structural materials in support of advanced fast reactors and AFCI. As you know, the alloy development effort has been initiated in recent months with the procurement of adequate quantities of the NF616 and HT-UPS alloys. As the test alloys become available in the coming days, mechanical testing, evaluation of optimizing treatments, and screening of environmental effects will be possible at a larger scale. It is therefore important to establish proper quality assurance protocols for this testing effort in a timely manner to ensure high technical quality throughout testing. A properly implemented quality assurance effort will also enable preliminary data taken in this effort to be qualified as NQA-1 during any subsequent licensing discussions for an advanced design or actual prototype. The objective of this report is to describe the quality assurance protocols that will be used for this effort. An essential first step in evaluating quality protocols is assessing the end use of the data. Currently, the advanced structural materials effort is part of a long-range, basic research and development effort and not, as yet, involved in licensing discussions for a specific reactor design. After consultation with Mark Vance (an ORNL QA expert) and based on the recently-issued AFCI QA requirements, the application of NQA-1 quality requirements will follow the guidance provided in Part IV, Subpart 4.2 of the NQA-1 standard (Guidance on Graded Application of QA for Nuclear-Related Research and Development). This guidance mandates the application of sound scientific methodology and a robust peer review process in all phases, allowing for the data to be qualified for use even if the programmatic mission changes to include licensing discussions of a specific design or prototype. ORNL has previously implemented a QA program dedicated to GNEP activities and based on an appropriately graded

  11. Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.

    Directory of Open Access Journals (Sweden)

    Mark R Soboleski

    Full Text Available The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1 highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca influenza viruses from 1977 or recombinant adenoviruses (rAd expressing 1934 nucleoprotein (NP and consensus matrix 2 (M2 (NP+M2-rAd. Antibodies against the M2 ectodomain (M2e were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.

  12. Quality assessment in in vivo NMR spectroscopy: V. Multicentre evaluation of prototype test objects and protocols for performance assessment in small bore MRS equipment

    DEFF Research Database (Denmark)

    Howe, F.A.; Canese, R; Podo, F

    1995-01-01

    This paper reports the results of multicentre studies aimed at designing, constructing, and evaluating prototype test objects for performance assessment in small-bore MRS systems, by utilizing the test protocols already proposed by the EEC COMAC-BME Concerted Action for clinical MRS equipment...... using ISIS as volume localization sequence in 31P MRS. The results suggested the interest of adopting some of these prototypes for improving the comparison of spectroscopy data obtained from different sites, for providing useful means of quality assurance in experimental MRS, and facilitating....... Three classes of test objects were considered: (1) a multicompartment test object for 31P MRS measurements performed with slice-selective sequences; (2) a two-compartment test object for volume-selection 1H MRS; and (3) two-compartment test objects for assessing the performance of experimental systems...

  13. Stat1 phosphorylation determines Ras oncogenicity by regulating p27 kip1.

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    Full Text Available Inactivation of p27 Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27 Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27 Kip1. Our work reveals a novel functional link between Stat1 and p27 Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors.

  14. Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1.

    Directory of Open Access Journals (Sweden)

    Ryan G Thomas

    Full Text Available An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure.We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1 and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05.These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection

  15. Experiment data report for Semiscale Mod-1 Test S-05-1 (alternate ECC injection test)

    International Nuclear Information System (INIS)

    Feldman, E.M.; Patton, M.L. Jr.; Sackett, K.E.

    1977-02-01

    Recorded test data are presented for Test S-05-1 of the Semiscale Mod-1 alternate ECC injection test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-05-1 was conducted from initial conditions of 2263 psia and 544 0 F to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the cold leg broken loop piping. During the test, cooling water was injected into the vessel lower plenum to simulate emergency core coolant injection in a PWR, with the flow rate based on system volume scaling

  16. Publication trends of study protocols in rehabilitation.

    Science.gov (United States)

    Jesus, Tiago S; Colquhoun, Heather L

    2017-09-04

    Growing evidence points for the need to publish study protocols in the health field. To observe whether the growing interest in publishing study protocols in the broader health field has been translated into increased publications of rehabilitation study protocols. Observational study using publication data and its indexation in PubMed. Not applicable. Not applicable. PubMed was searched with appropriate combinations of Medical Subject Headings up to December 2014. The effective presence of study protocols was manually screened. Regression models analyzed the yearly growth of publications. Two-sample Z-tests analyzed whether the proportion of Systematic Reviews (SRs) and Randomized Controlled Trials (RCTs) among study protocols differed from that of the same designs for the broader rehabilitation research. Up to December 2014, 746 publications of rehabilitation study protocols were identified, with an exponential growth since 2005 (r2=0.981; p<0.001). RCT protocols were the most common among rehabilitation study protocols (83%), while RCTs were significantly more prevalent among study protocols than among the broader rehabilitation research (83% vs. 35.8%; p<0.001). For SRs, the picture was reversed: significantly less common among study protocols (2.8% vs. 9.3%; p<0.001). Funding was more often reported by rehabilitation study protocols than the broader rehabilitation research (90% vs. 53.1%; p<0.001). Rehabilitation journals published a significantly lower share of rehabilitation study protocols than they did for the broader rehabilitation research (1.8% vs.16.7%; p<0.001). Identifying the reasons for these discrepancies and reverting unwarranted disparities (e.g. low rate of publication for rehabilitation SR protocols) are likely new avenues for rehabilitation research and its publication. SRs, particularly those aggregating RCT results, are considered the best standard of evidence to guide rehabilitation clinical practice; however, that standard can be improved

  17. The Hsp90 co-chaperones Sti1, Aha1, and P23 regulate adaptive responses to antifungal azoles

    Directory of Open Access Journals (Sweden)

    Xiaokui Gu

    2016-10-01

    Full Text Available Heat Shock Protein 90 (Hsp90 is essential for tumor progression in humans and drug resistance in fungi. However, the roles of its many co-chaperones in antifungal resistance are unknown. In this study, by susceptibility test of Neurospora crassa mutants lacking each of 18 Hsp90/Calcineurin system member genes (including 8 Hsp90 co-chaperone genes to antifungal drugs and other stresses, we demonstrate that the Hsp90 co-chaperones Sti1 (Hop1 in yeast, Aha1, and P23 (Sba1 in yeast were required for the basal resistance to antifungal azoles and heat stress. Deletion of any of them resulted in hypersensitivity to azoles and heat. Liquid chromatography–mass spectrometry (LC-MS analysis showed that the toxic sterols eburicol and 14α-methyl-3,6-diol were significantly accumulated in the sti1 and p23 deletion mutants after ketoconazole treatment, which has been shown before to led to cell membrane stress. At the transcriptional level, Aha1, Sti1, and P23 positively regulate responses to ketoconazole stress by erg11 and erg6, key genes in the ergosterol biosynthetic pathway. Aha1, Sti1, and P23 are highly conserved in fungi, and sti1 and p23 deletion also increased the susceptibility to azoles in Fusarium verticillioides. These results indicate that Hsp90-cochaperones Aha1, Sti1, and P23 are critical for the basal azole resistance and could be potential targets for developing new antifungal agents.

  18. Toxicokinetic Study for Investigation of Sex Differences in Internal Dosimetry of Jet Propulsion Fuel 8 (JP-8) in the Laboratory Rat

    Science.gov (United States)

    2013-07-26

    brain and observed cochlea concentrations of n-octane, n-decane, n-tetradecane, ethylbenzene , m-xylene and toluene in rats exposed to JP-8 (high...occur in combination with noise expo- sures (Department of the Army, 1998). The hydrocarbons ethylbenzene , toluene, and p-xylene, known to be present in...to supply JP-8 to the Cannon nose-only exposure system. Rats were exposed to JP-8 on a 52-position Cannon nose-only exposure system (Lab Products

  19. Compiling symbolic attacks to protocol implementation tests

    Directory of Open Access Journals (Sweden)

    Michael Rusinowitch

    2013-07-01

    Full Text Available Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically generating abstract attacks and converting them to concrete tests on protocol implementations. In particular we aim to improve previously proposed blackbox testing methods in order to discover automatically new attacks and vulnerabilities. As a proof of concept we have experimented our proposed architecture to detect a renegotiation vulnerability on some implementations of SSL/TLS, a protocol widely used for securing electronic transactions.

  20. Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and Breast Cancer Metastasis.

    Science.gov (United States)

    Nagahashi, Masayuki; Yamada, Akimitsu; Katsuta, Eriko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Hait, Nitai C; Allegood, Jeremy C; Tsuchida, Junko; Yuza, Kizuki; Nakajima, Masato; Abe, Manabu; Sakimura, Kenji; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

    2018-04-01

    Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod attenuated key proinflammatory cytokines, macrophage infiltration, and tumor progression induced by obesity. S1P produced in the lung premetastatic niche by tumor-induced SphK1 increased macrophage recruitment into the lung and induced IL6 and signaling pathways important for lung metastatic colonization. Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated signaling pathways in the lung induced by a high-fat diet, and it dramatically reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis, thereby prolonging survival. Taken together, our results establish a critical role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in obesity-related inflammation, formation of lung metastatic niches, and breast cancer metastasis, with potential implications for prevention and treatment. Significance: These findings offer a preclinical proof of concept that signaling by a sphingolipid may be an effective target to prevent obesity-related breast cancer metastasis. Cancer Res; 78(7); 1713-25. ©2018 AACR . ©2018 American Association for Cancer Research.

  1. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization[S

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M.; El-Shewy, Hesham M.; Sorci-Thomas, Mary G.; Thomas, Michael J.; Lopes-Virella, Maria F.; Luttrell, Louis M.; Hammad, Samar M.; Klein, Richard L.

    2017-01-01

    HDL normally transports about 50–70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration. PMID:27881715

  2. The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1

    Directory of Open Access Journals (Sweden)

    Melva Louisa

    2009-12-01

    Full Text Available Aim: Some carotenoids such as canthaxantin, astaxanthin and beta apo-8’-carotenal were reported to have modulatoryeffect on the cytochrome P450. The present study was conducted to investigate the effects of lycopene, a nonprovitamin A carotenoid, on microsomal cytochrome P450, CYP1A2 and CYP2E1.Methods: Total cytochrome P450 levels, CYP1A2 and CYP2E1-catalyzed reactions (acetanilide 4-hydroxylation and p-nitrophenol hydroxylation were studied in the liver microsomes of male Sprague Dawley rats. Microsomes were prepared using differential centrifugation combined with calcium aggregation method. Lycopene was orally administered in the dosages of 0, 25, 50 or 100 mg/kgBW/day for 14 days in a repeated fashion. Data were analyzed using ANOVA test.Results: Total cytochrome P450 level and acetanilide 4-hydroxylase activity were unaffected by any of the treatments. The CYP2E1 probe enzyme (p-nitrophenol hydroxylase was significantly reduced by repeated administration of 100mg/ kgBW/day lycopene (7.88 + 2.04 vs 12.26 + 2.77 n mol/min/mg prot.Conclusion: The present results suggest that lycopene does not affect the total cytochrome P450 or CYP1A2 activity but it inhibits the activity of CYP2E1 (p-nitrophenol hydroxylase in the rat. (Med J Indones 2009; 18: 233-8Keywords: lycopene, cytochrome P450, CYP1A2, CYP2E1

  3. Study of Stark Effect in n-doped 1.55 μm InN0.92yP1-1.92yBiy/InP MQWs

    Science.gov (United States)

    Bilel, C.; Chakir, K.; Rebey, A.; Alrowaili, Z. A.

    2018-05-01

    The effect of an applied electric field on electronic band structure and optical absorption properties of n-doped InN0.92y P1-1.92y Bi y /InP multiple quantum wells (MQWs) was theoretically studied using a self-consistent calculation combined with the 16-band anti-crossing model. The incorporation of N and Bi atoms into an InP host matrix leads to rapid reduction of the band gap energy covering a large infrared range. The optimization of the well parameters, such as the well/barrier widths, N/Bi compositions and doping density, allowed us to obtain InN0.92y P1-1.92y Bi y /InP MQWs operating at the wavelength 1.55 μm. Application of the electric field causes a red-shift of the fundamental transition energy T 1 accompanied by a significant change in the spatial distribution of confined electron density. The Stark effect on the absorption coefficient of n-doped InN0.92y P1-1.92y Bi y /InP MQWs was investigated. The Bi composition of these MQWs was adjusted for each electric field value in order to maintain the wavelength emission at 1.55 μm.

  4. Cense Explosion Test Program. Report 1. Cense 1. Explosions in Sandstone

    Science.gov (United States)

    1977-09-01

    series, "Analysis and Summary of CENSE Data." 10 * _ CHAPTER 2 APPROACH 2.1 DESCRIPTION OF TEST SITE An exposed outcrop of Kayenta sandstone with 180...ft/s seismic velocity previously determined (References 12-14) for the unweathered upper zone of the Kayenta sandstone. 16 I The P-wave propagation...Propagation along the horizontal radial was 8400 ft/s. The seismic velocity pre- viously determined for Kayenta sandstone in this area was 7500 ft/s

  5. Graded Exercise Testing in a Pediatric Weight Management Center: The DeVos Protocol.

    Science.gov (United States)

    Eisenmann, Joey C; Guseman, Emily Hill; Morrison, Kyle; Tucker, Jared; Smith, Lucie; Stratbucker, William

    2015-12-01

    In this article, we describe a protocol used to test the functional capacity of the obese pediatric patient and describe the peak oxygen consumption (VO2peak) of patients seeking treatment at a pediatric weight management center. One hundred eleven (mean age, 12.5 ± 3.0 years) patients performed a multistage exercise test on a treadmill, of which 90 (81%) met end-test criteria and provided valid VO2peak data. Peak VO2 was expressed: (1) in absolute terms (L·min(-1)); (2) as the ratio of the volume of oxygen consumed per minute relative to total body mass (mL·kg(-1)·min(-1)); and (3) as the ratio of the volume of oxygen consumed per minute relative to fat-free mass (mL·FFM·kg(-1)·min(-1)). Mean BMI z-score was 2.4 ± 0.3 and the mean percent body fat was 36.5 ± 9.7%. Absolute VO2peak (L·min(-1)) was significantly different between sexes; however, relative values were similar between sexes. Mean VO2peak was 25.7 ± 4.8 mL·kg(-1)·min(-1) with a range of 13.5-36.7 mL·kg(-1)·min(-1). Obese youth seeking treatment at a stage 3 pediatric weight management center exhibit low VO2peak. The protocol outlined here should serve as a model for similar programs interested in the submaximal and peak responses to exercise in obese pediatric patients.

  6. The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas.

    Science.gov (United States)

    Ngo, Teri-T B; Peng, Tien; Liang, Xing-Jie; Akeju, Oluwaseun; Pastorino, Sandra; Zhang, Wei; Kotliarov, Yuri; Zenklusen, Jean C; Fine, Howard A; Maric, Dragan; Wen, Patrick Y; De Girolami, Umberto; Black, Peter McL; Wu, Wells W; Shen, Rong-Fong; Jeffries, Neal O; Kang, Dong-Won; Park, John K

    2007-04-18

    Malignant gliomas are generally resistant to all conventional therapies. Notable exceptions are anaplastic oligodendrogliomas with loss of heterozygosity on chromosome 1p (1p+/-). Patients with 1p+/- anaplastic oligodendroglioma frequently respond to procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine. Because the underlying biologic basis for this clinical finding is unclear, we evaluated differentially expressed 1p-encoded proteins in 1p+/- and 1p+/+ malignant glioma cell lines and then examined whether their expression was associated with outcome of patients with anaplastic oligodendroglioma. We used a comparative proteomic screen of A172 (1p+/-) and U251 (1p+/+) malignant glioma cell lines to identify differentially expressed 1p-encoded proteins, including stathmin, a microtubule-associated protein. 1p+/- and 1p+/+ anaplastic oligodendroglioma specimens from 24 patients were assessed for stathmin expression by immunohistochemistry. The relationship between stathmin expression and clinical outcome was assessed with Kaplan-Meier analyses. RNA inhibition and cDNA transfection experiments tested effects of stathmin under- and overexpression, respectively, on the in vitro and in vivo resistance of malignant glioma cells to treatment with nitrosourea. For in vivo resistance studies, 36 mice with intracranial and 16 mice with subcutaneous xenograft tumor implants were used (one tumor per mouse). Flow cytometry was used for cell cycle analysis. Immunoblotting was used to assess protein expression. All statistical tests were two-sided. Decreased stathmin expression in tumors was statistically significantly associated with loss of heterozygosity in 1p (Pnitrosourea-treated mice carrying xenograft tumors. Median survival of mice with stathmin+/- tumors was 95 days (95% CI = 68.7 to 121.3 days) and that of mice with stathmin+/+ tumors was 64 days (95% CI = 58.2 to 69.8 days) (difference = 31 days, 95% CI = 4.1 to 57.9 days; PNitrosoureas induced

  7. Zac1, an Sp1-like protein, regulates human p21{sup WAF1/Cip1} gene expression in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Pei-Yao [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Hsieh, Tsai-Yuan [Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Liu, Shu-Ting; Chang, Yung-Lung [Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Lin, Wei-Shiang [Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Wang, Wei-Ming, E-mail: ades0431@ms38.hinet.net [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Huang, Shih-Ming, E-mail: shihming@ndmctsgh.edu.tw [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC (China)

    2011-12-10

    Zac1 functions as both a transcription factor and a transcriptional cofactor for p53, nuclear receptors (NRs) and NR coactivators. Zac1 might also act as a transcriptional repressor via the recruitment of histone deacetylase 1 (HDAC1). The ability of Zac1 to interact directly with GC-specific elements indicates that Zac1 possibly binds to Sp1-responsive elements. In the present study, our data show that Zac1 is able to interact directly with the Sp1-responsive element in the p21{sup WAF1/Cip1} gene promoter and enhance the transactivation activity of Sp1 through direct physical interaction. Our data further demonstrate that Zac1 might enhance Sp1-specific promoter activity by interacting with the Sp1-responsive element, affecting the transactivation activity of Sp1 via a protein-protein interaction, or competing the HDAC1 protein away from the pre-existing Sp1/HDAC1 complex. Finally, the synergistic regulation of p21{sup WAF1/Cip1} gene expression by Zac1 and Sp1 is mediated by endogenous p53 protein and p53-responsive elements in HeLa cells. Our work suggests that Zac1 might serve as an Sp1-like protein that directly interacts with the Sp1-responsive element to oligomerize with and/or to coactivate Sp1.

  8. Expression and clinical implication of Beclin1, HMGB1, p62, survivin, BRCA1 and ERCC1 in epithelial ovarian tumor tissues.

    Science.gov (United States)

    Ju, L-L; Zhao, C Y; Ye, K-F; Yang, H; Zhang, J

    2016-05-01

    The aim of the present study is to investigate the differential expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 protein in epithelial ovarian cancer (EOC) and to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. Expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC), 13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue. Beclin, p62 and ERCC1 expression was significantly higher in the EOC than the BET (p0.05). BRCA1 expression was lower in EOC than BET (pepithelial ovarian cancer.

  9. Prospective evaluation of a new protocol for the provisional use of perfusion imaging with exercise stress testing.

    Science.gov (United States)

    Duvall, W Lane; Savino, John A; Levine, Elliot J; Hermann, Luke K; Croft, Lori B; Henzlova, Milena J

    2015-02-01

    Previous literature suggests that myocardial perfusion imaging (MPI) adds little to the prognosis of patients who exercise >10 metabolic equivalents (METs) during stress testing. With this in mind, we prospectively tested a provisional injection protocol in emergency department (ED) patients presenting for the evaluation of chest pain in which a patient would not receive an injection of radioisotope if adequate exercise was achieved without symptoms and a negative ECG response. All patients who presented to the ED over a 5-year period who were referred for stress testing as part of their ED evaluation were included. Patients considered for a provisional protocol were: exercise stress, age heart rate ≥85%, ≥10 METs of exercise, no anginal symptoms during stress, and no ECG changes. Groups were compared based on stress test results, all-cause and cardiac mortality, follow-up cardiac testing, subsequent revascularization, and cost. A total of 965 patients were eligible with 192 undergoing exercise-only and 773 having perfusion imaging. After 41.6 ± 19.6 months of follow-up, all-cause mortality was similar in the exercise-only versus the exercise plus imaging group (2.6% vs. 2.1%, p = 0.59). There were no cardiac deaths in the exercise-only group. At 1 year there was no difference in the number of repeat functional stress tests (1.6% vs. 2.1%, p = 0.43), fewer angiograms (0% vs. 4.0%, p = 0.002), and a significantly lower cost ($65 ± $332 vs $506 ± $1,991, p = 0.002; values are in US dollars) in the exercise-only group. The radiation exposure in the exercise plus imaging group was 8.4 ± 2.1 mSv. A provisional injection protocol has a very low mortality, few follow-up diagnostic tests, and lower cost compared to standard imaging protocols. If adopted it would decrease radiation exposure, save time and decrease health-care costs without jeopardizing prognosis.

  10. Polymorphism in ficolin-1 (FCN1) gene is associated with an earlier ...

    Indian Academy of Sciences (India)

    ZILMA PEREIRA DOS ANJOSA1

    up based on the manufacture's protocol using 7500 Real-. Time PCR instrument ... tection against T1D onset (P value: 0.0003, OR: 0.53, 95%. CI = 0.38–0.75) as .... recruitment of leucocytes that produce a smaller quantity of ficolin 1 could ...

  11. Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans

    DEFF Research Database (Denmark)

    Cheon, Seon Ah; Bal, Jyotiranjan; Song, Yunkyoung

    2012-01-01

    p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal...... growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties...

  12. Influence of Whitening Gel Application Protocol on Dental Color Change

    Directory of Open Access Journals (Sweden)

    Taciana Marco Ferraz Caneppele

    2015-01-01

    Full Text Available Objectives. To evaluate the influence of different whitening protocols on the efficacy of 35% hydrogen peroxide (HP tooth whitening and gel pH and concentration. Material and Methods. Eighty-four enamel/dentin discs from bovine incisors were used. The baseline color was measured with a spectrophotometer. Two sessions of in-office whitening with 35% HP were performed under different protocols: G1: 3 applications of HP (10 min each per session; G2: 1 application of 30 min per session; G3: 1 application of 40 min per session, with no gel replenishment within session for groups 2 and 3. HP titration and pH evaluation at baseline, after 10, 30, and 40 min were also performed. The final color was measured 24 h after the 1st and 2nd whitening sessions. Data were submitted to Repeated Measures ANOVA and Tukey’s test. Results. For color evaluation, no differences were observed among groups after two sessions. HP titration showed no drop on concentration after 10, 30, or 40 min. The pH was 5.54 at baseline and 5.41 after 40 min. Conclusion. Replenishment or extended application time of in-office whitening gel does not affect gel pH and concentration, a fact that supports the similar effectiveness of whitening observed among the tested protocols.

  13. Measurements in large JP-4 pool fires

    International Nuclear Information System (INIS)

    Keltner, N.R.; Kent, L.A.; Schneider, M.E.

    1987-01-01

    Over the past four years, Sandia National Laboratories has conducted a number of large pool fire tests to evaluate the design of radioactive material (RAM) shipping containers. Some of these tests have been designed to define the thermal environment and some have been used for certification testing. In each test there have been a number of fire diagnostic measurements. The simplest sets of diagnostics have involved measurements of temperature at several elevations on arrays of towers, measurements of hot wall heat flux with small calorimeters suspended from the towers, the average fuel recession rate, and the wind speed and direction. The most complex sets of diagnostics have included the above and in various tests added radiometers in the lower flame zone, centerline velocity measurements at a number of elevations, radiometers and calorimeters at the fuel surface, large cylindrical and flat plate calorimeters, infrared imaging, time resolved fuel recession rates, and a variety of soot particle concentration and size measurements made in the plume with a tethered balloon and an instrumented airplane. All of the large fires have been conducted in a 9.1 m by 18.3 m pool using JP-4 as the fuel. Typical duration is one-half hour. Covering all of the results is beyond the scope of a single paper. Conditionally sampled temperature and velocity measurements from one fire will be presented; for this fire, a 20 cm layer of fuel was floated on 61 cm of water. Pool surface heat flux, fuel recession rate data, and smoke emission data from a second fire are given. Because the wind has a strong effect on the temperature and velocity measurements, conditional sampling has been used to try to obtain data during periods of low winds. 10 refs., 3 figs

  14. SUN family proteins Sun4p, Uth1p and Sim1p are secreted from Saccharomyces cerevisiae and produced dependently on oxygen level.

    Directory of Open Access Journals (Sweden)

    Evgeny Kuznetsov

    Full Text Available The SUN family is comprised of proteins that are conserved among various yeasts and fungi, but that are absent in mammals and plants. Although the function(s of these proteins are mostly unknown, they have been linked to various, often unrelated cellular processes such as those connected to mitochondrial and cell wall functions. Here we show that three of the four Saccharomyces cerevisiae SUN family proteins, Uth1p, Sim1p and Sun4p, are efficiently secreted out of the cells in different growth phases and their production is affected by the level of oxygen. The Uth1p, Sim1p, Sun4p and Nca3p are mostly synthesized during the growth phase of both yeast liquid cultures and colonies. Culture transition to slow-growing or stationary phases is linked with a decreased cellular concentration of Sim1p and Sun4p and with their efficient release from the cells. In contrast, Uth1p is released mainly from growing cells. The synthesis of Uth1p and Sim1p, but not of Sun4p, is repressed by anoxia. All four proteins confer cell sensitivity to zymolyase. In addition, Uth1p affects cell sensitivity to compounds influencing cell wall composition and integrity (such as Calcofluor white and Congo red differently when growing on fermentative versus respiratory carbon sources. In contrast, Uth1p is essential for cell resistance to boric acids irrespective of carbon source. In summary, our novel findings support the hypothesis that SUN family proteins are involved in the remodeling of the yeast cell wall during the various phases of yeast culture development and under various environmental conditions. The finding that Uth1p is involved in cell sensitivity to boric acid, i.e. to a compound that is commonly used as an important antifungal in mycoses, opens up new possibilities of investigating the mechanisms of boric acid's action.

  15. Comparative analysis between P1 and B1 equations for neutron moderation

    International Nuclear Information System (INIS)

    Martinez, Aquilino Senra; Silva, Fernando Carvalho da; Cardoso, Carlos Eduardo Santos

    2000-01-01

    In order to calculate the neutron flux in nuclear reactors, B1 or P1 equations are solved by numerical methods for several groups of energy. The neutron fluxes obtained from the solutions of the B1 and P1 equations are similar when they are applied to large nuclear power reactors. However, an important difference between the two fluxes is that the system of P1 equations uses one more approximation than the B1 system and then, its flux is less precise. The present work shows the relations between both equations and analyzes for what conditions the two equations systems are equivalent. Furthermore, this equations are numerically solved in 54 groups of energy for a quadrangular arrange. (author)

  16. 2009 pandemic influenza A (H1N1 virus outbreak and response--Rwanda, October, 2009-May, 2010.

    Directory of Open Access Journals (Sweden)

    Justin Wane

    Full Text Available BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1pdm09 (pH1N1 was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL. Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532 of specimens tested influenza positive; of these 96% (n = 510 were influenza A and 4% (n = 22 were influenza B. Of cases testing influenza A positive, 96.8% (n = 494, 3% (n = 15, and 0.2% (n = 1 were A(H1N1pdm09, Seasonal A(H3 and Seasonal A(non-subtyped, respectively. Among laboratory-confirmed cases, 263 (53.2% were children <15 years and 275 (52% were female. In total, 58 (12% cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days. All cases recovered and there were no deaths. Overall, 339 (68% confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532 were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532, asthma 0.8% (4/532, cardiac disease 1.5% (8/532, pregnancy 0.6% (3/532, diabetes mellitus 0.4% (2/532, and chronic malnutrition 0.8% (4/532. CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to

  17. From proton nuclear magnetic resonance spectra to pH. Assessment of {sup 1}H NMR pH indicator compound set for deuterium oxide solutions

    Energy Technology Data Exchange (ETDEWEB)

    Tynkkynen, Tuulia, E-mail: tuulia.tynkkynen@uku.fi [Laboratory of Chemistry, Department of Biosciences, University of Kuopio, PO Box 1627, 70211 Kuopio (Finland); Tiainen, Mika; Soininen, Pasi; Laatikainen, Reino [Laboratory of Chemistry, Department of Biosciences, University of Kuopio, PO Box 1627, 70211 Kuopio (Finland)

    2009-08-19

    In this study, a protocol for pH determination from D{sub 2}O samples using {sup 1}H NMR pH indicator compounds was developed and assessed by exploring the pH-dependency of 13 compounds giving pH-dependent {sup 1}H NMR signals. The indicators cover the pH range from pH* 0 to 7.2. Equations to transform the indicator chemical shifts to pH estimates are given here for acetic acid, formic acid, chloroacetic acid, dichloroacetic acid, creatine, creatinine, glycine, histidine, 1,2,4-triazole, and TSP (2,2,3,3-tetradeutero-3-(trimethylsilyl)-propionic acid). To characterize the method in presence of typical solutes, the effects of common metabolites, albumin and ionic strength were also evaluated. For the ionic strengths, the effects were also modelled. The experiments showed that the use of pH sensitive {sup 1}H NMR chemical shifts allows the pH determination of typical metabolite solutions with accuracy of 0.01-0.05 pH units. Also, when the ionic strength is known with accuracy better than 0.1 mol dm{sup -3} and the solute concentrations are low, pH{sub nmr}{sup *} (the NMR estimate of pH) can be assumed to be within 0.05 pH units from potentiometrically determined pH.

  18. Search for stopped gluinos from p-anti-p collisions at s**(1/2) = 1.96 TeV

    Czech Academy of Sciences Publication Activity Database

    Abazov, V. M.; Abbott, B.; Abolins, M.; Kupčo, Alexander; Lokajíček, Miloš; Šimák, Vladislav

    2007-01-01

    Roč. 99, č. 13 (2007), 131801/1-131801/7 ISSN 0031-9007 R&D Projects: GA MŠk 1P04LA210; GA MŠk 1P05LA257 Institutional research plan: CEZ:AV0Z10100502 Keywords : supersymmetry * gluino * neutralino * D0 * DZero Subject RIV: BF - Elementary Particle s and High Energy Physics Impact factor: 6.944, year: 2007

  19. A1C Test and Diabetes

    Science.gov (United States)

    ... Diagnosis The A1C Test & Diabetes The A1C Test & Diabetes On this page: What is the A1C test? ... the A1C test used to diagnose type 2 diabetes and prediabetes? Health care professionals can use the ...

  20. Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

    DEFF Research Database (Denmark)

    Savelyeva, I.; Dobbelstein, M.

    2011-01-01

    to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

  1. Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

    Science.gov (United States)

    Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

    2011-01-01

    Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

  2. Optimizing a Treadmill Ramp Protocol to Evaluate Aerobic Capacity of Hemiparetic Poststroke Patients.

    Science.gov (United States)

    Bernardes, Wendell L; Montenegro, Rafael A; Monteiro, Walace D; de Almeida Freire, Raul; Massaferri, Renato; Farinatti, Paulo

    2018-03-01

    Bernardes, WL, Montenegro, RA, Monteiro, WD, de Almeida Freire, R, Massaferri, R, and Farinatti, P. Optimizing a treadmill ramp protocol to evaluate aerobic capacity of hemiparetic poststroke patients. J Strength Cond Res 32(3): 876-884, 2018-A correct assessment of cardiopulmonary capacity is important for aerobic training within motor rehabilitation of poststroke hemiparetic patients (PSHPs). However, specific cardiopulmonary exercise testing (CPET) for these patients are scarce. We proposed adaptations in a protocol originally developed for PSHPs by Ovando et al. (CPET1). We hypothesized that our adapted protocol (CPET2) would improve the original test, by preventing early fatigue and increasing patients' peak performance. Eleven PSHPs (52 ± 14 years, 10 men) performed both protocols. CPET2 integrated changes in final speed (100-120% vs. 140% maximal speed in 10-m walking test), treadmill inclination (final inclination of 5 vs. 10%), and estimated test duration (10 vs. 8 minutes) to smooth the rate of workload increment of CPET1. Peak oxygen uptake (V[Combining Dot Above]O2peak) (20.3 ± 6.1 vs. 18.6 ± 5.0 ml·kg·min; p = 0.04), V[Combining Dot Above]O2 at gas exchange transition (V[Combining Dot Above]O2-GET) (11.5 ± 2.9 vs. 9.8 ± 2.0 ml·kg·min; p = 0.04), and time to exhaustion (10 ± 3 vs. 6 ± 2 minutes; p higher in CPET2 than in CPET1. Slopes and intercepts of regressions describing relationships between V[Combining Dot Above]O2 vs. workload, heart rate vs. workload, and V[Combining Dot Above]O2 vs. heart rate were similar between CPETs. However, standard errors of estimates obtained for regressions between heart rate vs. workload (3.0 ± 1.3 vs. 3.8 ± 1.0 b·min; p = 0.004) and V[Combining Dot Above]O2 vs. heart rate (6.0 ± 2.1 vs. 4.8 ± 2.4 ml·kg·min; p = 0.05) were lower in CPET2 than in CPET1. In conclusion, the present adaptations in Ovando's CPET protocol increased exercise tolerance of PSHPs, eliciting higher V[Combining Dot Above]O2peak

  3. S1P and the birth of platelets

    Science.gov (United States)

    Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

    2012-01-01

    Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P1 receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P1 receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12–CXCR4 axis. Pharmacologic modulation of the S1P1 receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P4 receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P1 duet that could potentially be harnessed for clinical translation. PMID:23166370

  4. Computer program /P1-GAS/ calculates the P-0 and P-1 transfer matrices for neutron moderation in a monatomic gas

    Science.gov (United States)

    Collier, G.; Gibson, G.

    1968-01-01

    FORTRAN 4 program /P1-GAS/ calculates the P-O and P-1 transfer matrices for neutron moderation in a monatomic gas. The equations used are based on the conditions that there is isotropic scattering in the center-of-mass coordinate system, the scattering cross section is constant, and the target nuclear velocities satisfy a Maxwellian distribution.

  5. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    Science.gov (United States)

    Zhang, Xun E; Adderley, Shaquria P; Breslin, Jerome W

    2016-01-01

    Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

  6. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    Directory of Open Access Journals (Sweden)

    Xun E Zhang

    Full Text Available Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC or human dermal microvascular endothelial cells (HDMEC were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER using an electrical cell-substrate impedance sensor (ECIS. The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

  7. Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1α mRNA response in human skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina; Gunnarsson, Thomas Gunnar Petursson; Hostrup, Morten

    2016-01-01

    This study tested the hypothesis that elevated plasma adrenaline or metabolic stress enhances exercise-induced PGC-1α mRNA and intracellular signaling in human muscle. Trained (VO2-max: 53.8 ± 1.8 mL min(-1) kg(-1)) male subjects completed four different exercise protocols (work load of the legs...... exercise than at rest in all protocols, and higher (P adrenaline nor muscle metabolic stress determines the magnitude of PGC-1α mRNA response in human muscle. Furthermore, higher exercise-induced changes in AMPK, p38, and CREB...

  8. Preparation data of the bromodomains BRD3(1, BRD3(2, BRD4(1, and BRPF1B and crystallization of BRD4(1-inhibitor complexes

    Directory of Open Access Journals (Sweden)

    Martin Hügle

    2016-06-01

    Full Text Available This article presents detailed purification procedures for the bromodomains BRD3(1, BRD3(2, BRD4(1, and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1 and BRD4(1 in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC and by differential scanning fluorimetry (DSF as well as structural characterizations of BRD4(1 inhibitor complexes (PDB codes: PDB: 4LYI, PDB: 4LZS, PDB: 4LYW, PDB: 4LZR, PDB: 4LYS, PDB: 5D24, PDB: 5D25, PDB: 5D26, PDB: 5D3H, PDB: 5D3J, PDB: 5D3L, PDB: 5D3N, PDB: 5D3P, PDB: 5D3R, PDB: 5D3S, PDB: 5D3T. These data have been reported previously and are discussed in more detail elsewhere [1,2].

  9. Experiment data report for semiscale Mod-1 test S-04-1 (baseline ECC test)

    International Nuclear Information System (INIS)

    Crapo, H.S.; Collins, B.L.; Sackett, K.E.

    1976-09-01

    Recorded test data are presented for Test S-04-1 of the Semiscale Mod-1 Baseline ECC Test Series. This test is among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor system. Test S-04-1 was conducted from an initial cold leg fluid temperature of 542 0 F and an initial pressure of 2,263 psia. A simulated double-ended offset shear cold leg break was used to investigate the system response to a depressurization and reflood transient using system volume scaled coolant injection parameters. System flow was set to achieve a core fluid temperature differential of 66 0 F at a full core power of 1.6 MW. The flow resistance of the intact loop was based on core area scaling. An electrically heated core with a flat radial power profile was used in the pressure vessel to simulate the effects of a nuclear core. During system depressurization, core power was reduced from the initial level of 1.6 MW in such a manner as to simulate the surface heat flux response of nuclear fuel rods until such time that departure from nucleate boiling might occur. Blowdown to the pressure suppression system was accompanied by simulated emergency core cooling injection into both the intact and broken loops. Coolant injection was continued until test termination at 200 seconds after initiation of blowdown

  10. Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.

    Science.gov (United States)

    Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D

    2017-12-01

    Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH) 2 D 3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH) 2 D 3 for 48 or 72 h reduces S1PR2 (4-fold; S1P did not inhibit the migration of cells exposed to 1,25(OH) 2 D 3 (p S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα 12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Electric Vehicle Communications Standards Testing and Validation - Phase II: SAE J2931/1

    Energy Technology Data Exchange (ETDEWEB)

    Pratt, Richard M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gowri, Krishnan [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-01-15

    Vehicle to grid communication standards enable interoperability among vehicles, charging stations and utility providers and provide the capability to implement charge management. Several standards initiatives by the Society of Automobile Engineers (SAE), International Standards Organization and International Electrotechnical Commission (ISO/IEC), and ZigBee/HomePlug Alliance are developing requirements for communication messages and protocols. Recent work by the Electric Power Research Institute (EPRI) in collaboration with SAE and automobile manufacturers has identified vehicle to grid communication performance requirements and developed a test plan as part of SAE J2931/1 committee work. This laboratory test plan was approved by the SAE J2931/1 committee and included test configurations, test methods, and performance requirements to verify reliability, robustness, repeatability, maximum communication distance, and authentication features of power line carrier (PLC) communication modules at the internet protocol layer level. The goal of the testing effort was to select a communication technology that would enable automobile manufacturers to begin the development and implementation process. The EPRI/Argonne National Laboratory (ANL)/Pacific Northwest National Laboratory (PNNL) testing teams divided the testing so that results for each test could be presented by two teams, performing the tests independently. The PNNL team performed narrowband PLC testing including the Texas Instruments (TI) Concerto, Ariane Controls AC-CPM1, and the MAXIM Tahoe 2 evaluation boards. The scope of testing was limited to measuring the vendor systems communication performance between Electric Vehicle Support Equipment (EVSE) and plug-in electric vehicles (PEV). The testing scope did not address PEV’s CAN bus to PLC or PLC to EVSE (Wi-Fi, cellular, PLC Mains, etc.) communication integration. In particular, no evaluation was performed to delineate the effort needed to translate the IPv6

  12. Molecular components in P-wave charmed-strange mesons

    CERN Document Server

    Ortega, Pablo G.

    2016-10-26

    Results obtained by various experiments show that the $D_{s0}^{\\ast}(2317)$ and $D_{s1}(2460)$ mesons are very narrow states located below the $DK$ and $D^{\\ast}K$ thresholds, respectively. This is markedly in contrast with the expectations of naive quark models and heavy quark symmetry. Motivated by a recent lattice study which addresses the mass shifts of the $c\\bar{s}$ ground states with quantum numbers $J^{P}=0^{+}$ ($D_{s0}^{\\ast}(2317)$) and $J^{P}=1^{+}$ ($D_{s1}(2460)$) due to their coupling with $S$-wave $D^{(\\ast)}K$ thresholds, we perform a similar analysis within a nonrelativistic constituent quark model in which quark-antiquark and meson-meson degrees of freedom are incorporated. The quark model has been applied to a wide range of hadronic observables and thus the model parameters are completely constrained. The coupling between quark-antiquark and meson-meson Fock components is done using a modified version of the $^{3}P_{0}$ decay model. We observe that the coupling of the $0^{+}$ $(1^{+})$ mes...

  13. Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols

    DEFF Research Database (Denmark)

    Andersen, Mette Klarskov; Autio, Kirsi; Barbany, Gisela

    2011-01-01

    The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19)t(1;19)-positive BCP ALL treated on two successive Nordic...... Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1·8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional...... and 10 years was 0·85 and 0·82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS...

  14. Interobserver and test-retest reproducibility of T1ρ and T2 mesurements of lumber intervertebral discs by 3t magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Yeon Hwa; Yoon, Choon Sik; Eun, Na Lae; Kim, Sung Jin; Chung, Tae Sub [Dept. of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Hwang, Moon Jung [GE Health Care, Seoul (Korea, Republic of); Yoo, Hanna [Biostatistics Collaboration Lab, Yonsei University College of Medicine, Seoul (Korea, Republic of); Peter, Robert D. [GE Health Care, Milwaukee (United States); Lee, Young Han; Suh, Jin Suck [Dept. of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-11-15

    To investigate the interobserver and test-retest reproducibility of T1ρ and T2 measurements of lumbar intervertebral discs using 3T magnetic resonance imaging (MRI). This study included a total of 51 volunteers (female, 26; male, 25; mean age, 54 ± 16.3 years) who underwent lumbar spine MRI with a 3.0 T scanner. Amongst these subjects, 40 underwent repeat T1ρ and T2 measurement acquisitions with identical image protocol. Two observers independently performed the region of interest measurements in the nuclei pulposi of the discs from L1-2 through L5-S1 levels. Statistical analysis was performed using intraclass correlation coefficient (ICC) with a two-way random model of absolute agreement. Comparison of the ICC values was done after acquisition of ICC values using Z test. Statistical significance was defined as p value < 0.05. The ICCs of interobserver reproducibility were 0.951 and 0.672 for T1ρ and T2 mapping, respectively. The ICCs of test-retest reproducibility (40 subjects) for T1ρ and T2 measurements were 0.922 and 0.617 for observer A and 0.914 and 0.628 for observer B, respectively. In the comparison of the aforementioned ICCs, ICCs of interobserver and test-retest reproducibility for T1ρ mapping were significantly higher than T2 mapping (p < 0.001). The interobserver and test-retest reproducibility of T1ρ mapping were significantly higher than those of T2 mapping for the quantitative assessment of nuclei pulposi of lumbar intervertebral discs.

  15. Mark 1 Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Mark I Test Facility is a state-of-the-art space environment simulation test chamber for full-scale space systems testing. A $1.5M dollar upgrade in fiscal year...

  16. IVOA Credential Delegation Protocol Version 1.0

    Science.gov (United States)

    Plante, Raymond; Graham, Matthew; Rixon, Guy; Taffoni, Giuliano; Plante, Raymond; Graham, Matthew

    2010-02-01

    The credential delegation protocol allows a client program to delegate a user's credentials to a service such that that service may make requests of other services in the name of that user. The protocol defines a REST service that works alongside other IVO services to enable such a delegation in a secure manner. In addition to defining the specifics of the service protocol, this document describes how a delegation service is registered in an IVOA registry along with the services it supports. The specification also explains how one can determine from a service registration that it requires the use of a supporting delegation service.

  17. User's manual for THYDE-P1

    International Nuclear Information System (INIS)

    Asahi, Yoshiro

    1982-04-01

    THYDE-P1 is a computer code applicable to LWR (light water reactor) plant dynamics in response to various disturbances. This work is the user's mannual of THYDE-P1 (version SV02L03). The input requirements, steady state adjustment, execution of runs and output specifications are described. (author)

  18. Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Harrison David J

    2007-11-01

    Full Text Available Abstract Background TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how Rb-deficiency would affect responses to TGFβ-induced cell cycle arrest. Results Primary hepatocytes isolated from Rb-floxed mice were infected with an adenovirus expressing CRE-recombinase to delete the Rb gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes, cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling. Rb is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some Rb-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21Cip1 and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21Cip and P53 work through the same pathway to regulate G1/S in response to TGFβ. In Rb-deficient cells however, p53 but not p21Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. Conclusion The present results show that otherwise genetically normal hepatocytes with disabled p53, p21Cip1 or Rb genes respond less well to the antiproliferative effects of TGFβ. As the function of

  19. A lifetime measurement of the 1s2p 3P1 level in helium-like Mg and Al

    International Nuclear Information System (INIS)

    Armour, I.A.; Silver, J.D.; Traebert, E.; Oxford Univ.

    1981-01-01

    The lifetimes of the 1s2p 3 P 1 levels of helium-like magnesium and aluminium have been measured by the beam-foil decay curve technique. The 1s 2 -1s2p transitions were observed with a curved-crystal x-ray spectrometer. Decay curves taken under systematically varied conditions have been evaluated using several techniques including a cascade model. The results are in agreement with most of the theoretical predictions. (author)

  20. Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation.

    Science.gov (United States)

    Grenald, Shaness A; Doyle, Timothy M; Zhang, Hong; Slosky, Lauren M; Chen, Zhoumou; Largent-Milnes, Tally M; Spiegel, Sarah; Vanderah, Todd W; Salvemini, Daniela

    2017-09-01

    Metastatic bone pain is the single most common form of cancer pain and persists as a result of peripheral and central inflammatory, as well as neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P). Intriguingly, de novo sphingolipid biosynthesis was increased as shown by the elevations of dihydro-ceramides and dihydro-S1P. We next identified the S1P receptor subtype 1 (S1PR1) as a novel target for therapeutic intervention. Intrathecal or systemic administration of the competitive and functional S1PR1 antagonists, TASP0277308 and FTY720/Fingolimod, respectively, attenuated cancer-induced spontaneous flinching and guarding. Inhibiting CIBP by systemic delivery of FTY720 did not result in antinociceptive tolerance over 7 days. FTY720 administration enhanced IL-10 in the lumbar ipsilateral spinal cord of CIBP animals and intrathecal injection of an IL-10 neutralizing antibody mitigated the ability of systemic FTY720 to reverse CIBP. FTY720 treatment was not associated with alterations in bone metabolism in vivo. Studies here identify a novel mechanism to inhibit bone cancer pain by blocking the actions of the bioactive metabolites S1P and dihydro-S1P in lumbar spinal cord induced by bone cancer and support potential fast-track clinical application of the FDA-approved drug, FTY720, as a therapeutic avenue for CIBP.

  1. Effect of insulin therapy and dietary adjustments on safety and performance during simulated soccer tests in people with type 1 diabetes: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Calvo-Marín, Javier; Torrealba-Acosta, Gabriel; Campbell, Matthew; Gaboury, Jesse; Ali, Ajmol; Chen-Ku, Chih Hao

    2017-07-20

    Despite the reduction in glycemic derangement in patients with type 1 diabetes mellitus (T1D) through dietary and therapeutic adjustments implemented before, during and after continuous exercise, evidence for its effectiveness with intermittent forms of exercise, such as soccer, is still lacking. We designed a study protocol for a randomized, crossover, double-blinded, controlled trial, for the evaluation of the effect that a strategy of dietary and therapeutic modifications may have on safety and performance of persons with T1D in soccer training sessions and cognitive testing. Inclusion criteria comprise: age older than 18 years, more than 2 years since T1D diagnosis, low C-peptide level, a stable insulin regimen, HbA1c less than 9.0% and regular participation in soccer activities. Our primary outcome evaluates safety regarding hypoglycemia events in patients using dietary and therapeutic adjustments, compared with the performance under the implementation of current American Diabetes Association (ADA) usual recommendations for nutritional and pharmacological adjustments for exercise. Additionally, we will evaluate as secondary outcomes: soccer performance, indexed by performance in well-established soccer skill tests, cognitive functions (indexed by Stroop, digital vigilance test (DVT), Corsi block-tapping task (CBP), and rapid visual information processing (RVIP) tests), and glycemic control measured with a continuous glucose monitor (CGM). Dietary and insulin adjustments standardized under a 4-step method strategy have never been tested in a clinical trial setting with intermittent forms of exercise, such as soccer. We hypothesize that through this strategy we will observe better performance by persons with T1D in soccer and cognitive evaluations, and more stable control of glycemic parameters before, during and after exercise execution, indexed by CGM measurements. ISRCTN, ISRCTN17447843. Registered on 5 January 2017.

  2. Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. METHODS: In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients. RESULTS: In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity. CONCLUSION: Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

  3. Intrinsic remediation of JP-4 fuel in soil and ground water

    International Nuclear Information System (INIS)

    Schmithorst, W.L. Jr.; Vardy, J.A.

    1995-01-01

    Intrinsic remediation methods were employed to remediate soil and ground water contaminated by JP-4 fuel at the United States Coast Guard (USCG) Support Center facility in Elizabeth City, North Carolina. By the time the release was discovered, non-aqueous phase JP-4 fuel was detected in ground water over an area of approximately 8,000 square feet. In addition, concentrations of dissolved BTEX in ground water exceeded 5,000 microg/L. Tight clays present in the upper two meters of the aquifer, underlain by highly transmissive sands, prevented remediation of the JP-4 by conventional treatment methods. Therefore, a system of air injection and air extraction wells were installed that simultaneously depressed the water table and extracted hydrocarbon vapors. The conceptual idea, developed by the EPA RS Kerr Environmental Laboratory (RSKERL) in Ada, Oklahoma, is to stimulate rapid intrinsic biodegradation of the JP-4 fuel compounds. Subsequent biorespiration measurements indicated that the fuel compounds were being rapidly biodegraded. Upon removal of the non aqueous JP-4 compounds, an investigation was conducted to determine if the aquifer had an adequate assimilative capacity to support natural aerobic and anaerobic biodegradation of the contaminants. Analysis of ground water samples collected using a cone penetrometer and a direct-push sampling device indicate a sufficient concentration of electron acceptors to support natural biodegradation of the JP-4 compounds

  4. The continuing saga of the /sup 1/P/sub 1/ (q-barq) mesonic states

    International Nuclear Information System (INIS)

    Dalitz, R.H.; Tuan, S.F.

    1986-01-01

    The mesonic states predicted by the quark model to have the structure (q-barq) do not allow all combinations possible for the quantum numbers (JPC). The happy situation for the /sup 3/P/sub J/ states does not hold for the /sup 1/P/sub 1/ state. The experimenter is therefore faced by a double difficulty, the difficulty of forming the /sup 1/P/sub 1/ through the channels available to him and the difficulty of detecting the /sup 1/P/sub 1/ state when it is formed. The difficulty about the detection and study of /sup 1/P/sub 1/ states is not intrinsic but circumstantial. It is not intrinsic because the B-meson is readily produced and studied, the same being true for Q/sub B/, although this has been a more confused situation because of the mixing between the Q/sub A/ and Q/sub B/ states. Porter has devoted considerable attention to the search for the /sup 1/P/sub 1/ (c-barc) state and the authors outline that discussion in this paper. They also describe the formation of the state Psi' (3685), since this has a large cross section in e/sup +/e/sup -/ annihilation, and to look for the /sup 1/P/sub 1/ state as a product among its decay modes

  5. 1P1 heavy quarkonia production in hadron-hadron collisions

    International Nuclear Information System (INIS)

    Alanakyan, R.A.; Dul'yan, L.S.; Grigoryan, S.G.; Matinyan, S.G.

    1987-01-01

    The production of 1 P 1 -quarkonia (charmonium, bottomonium and toponium) with large transverse momenta is studied in collisions of ultrahigh-energy pp and pp-bar beams. The analysis was carried out in the framework of gluon-gluon fusion mechanism and nonrelativistic quarkonium model

  6. Event Shapes in $p\\bar p$ Collisions at $\\sqrt{s} = 1.96$ TeV

    Energy Technology Data Exchange (ETDEWEB)

    Atkins, Scott [Louisiana Tech Univ., Ruston, LA (United States)

    2012-08-01

    This dissertation presents the analysis of nine different event shapes measured in high energy p$\\bar{p}$ collisions. An event shape can be defined as an event-based quantity that measures how the final energies are distributed in the final event. This analysis will test strong interactions as described by Quantum Chromodynamics (QCD), through their implementation in different Monte Carlo-based models. Each of the event shapes provides information about the flow of energy in QCD events and about the hadronic final states that occur in p$\\bar{p}$ particle collisions, thus allowing the study of the dynamics of QCD multijet events. Any deviation of an event shape from zero will be indicative of higher-order effects, meaning that more than the two jets were produced in the event. For each of the event shapes, both normalized differential distributions ( 1/σ dσ/dX) and average event shapes ($\\bar{X}$σ) were measured, where X is the event shape and σ is the cross section. This analysis uses 0.7 fb-1 of data taken between 2004 and 2006 by the DØ detector located at the Fermi National Accelerator Lab (Fermilab) in Batavia, IL, using p$\\bar{p}$ collisions at a center-of-mass energy of √s = 1.96 TeV.

  7. Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

    Directory of Open Access Journals (Sweden)

    Kaipeng Huang

    Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

  8. A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1-p15 microdeletion syndrome: Clinical and molecular analysis.

    Science.gov (United States)

    Mimouni-Bloch, Aviva; Yeshaya, Josepha; Kahana, Sarit; Maya, Idit; Basel-Vanagaite, Lina

    2015-11-01

    Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 microdeletion syndrome. Children with this syndrome generally share certain features including microcephaly, developmental delay, facial dysmorphism, urogenital and skeletal abnormalities. We present a child with a de-novo interstitial 1665 kb duplication of 2p16.1-p15. Clinical features of this child are distinct from those of children with the 2p16.1-p15 microdeletion syndrome, specifically the head circumference which is within the normal range and mild intellectual disability with absence of autistic behaviors. Microduplications many times bear milder clinical phenotypes in comparison with corresponding microdeletion syndromes. Indeed, as compared to the microdeletion syndrome patients, the 2p16.1-p15 microduplication seems to have a milder cognitive effect and no effect on other body systems. Limited information available in genetic databases about cases with overlapping duplications indicates that they all have abnormal developmental phenotypes. The involvement of genes in this location including BCL11A, USP34 and PEX13, affecting fundamental developmental processes both within and outside the nervous system may explain the clinical features of the individual described in this report. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. Art. 1 Eerste Protocol EVRM

    NARCIS (Netherlands)

    Poelmann, E.

    2014-01-01

    Het recht op bezit is niet in het Europees Verdrag ter bescherming van de rechten van de mens en de fundamentele vrijheden (hierna: EVRM) neergelegd, maar in het Eerste Protocol daarbij (hierna: EP), dat in 1954 in werking is getreden. Het is van belang voor ogen te houden dat de Tweede Wereldoorlog

  10. Some spherical analysis related to the pairs (U (n), Hn) and (U (p, q ...

    Indian Academy of Sciences (India)

    )-invariant, left invariant differential operators on Hn is commutative. It is generated by. P = p. ∑ j=1. (X2 j + Y2 j ) − n. ∑ j=p+1 (X2 j + Y2 j ) and T = ∂∂t where {T,X1,...,Xn,Y1,...,Yn} denotes the standard basis of the Lie algebra of Hn. That is ...

  11. Improvement in luminance of light-emitting diode using InP/ZnS quantum dot with 1-dodecanethiol ligand

    Science.gov (United States)

    Fukuda, Takeshi; Sasaki, Hironao

    2018-03-01

    We present the synthesis protocol of a red emissive InP/ZnS quantum dot with a 1-dodecanthiol ligand and its application to a quantum dot light-emitting diode. The ligand change from oleylamine to 1-dodecanthiol, which were connected around the InP/ZnS quantum dot, was confirmed by Fourier-transform infrared spectroscopy and thermal analysis. The absorption peak was blue-shifted by changing 1-dodecanthiol ligands from oleylamine ligands to prevent the unexpected nucleation of the InP core. In addition, the luminance of the light-emitting device was improved by using the InP/ZnS quantum dot with 1-dodecanthiol ligands, and the maximum current efficiency of 7.2 × 10-3 cd/A was achieved. The 1-dodecanthiol ligand is often used for capping to reduce the number of surface defects and/or prevent unexpected core growth, resulting in reduced Auger recombination. This result indicates that 1-dodecanthiol ligands prevent the deactivation of excitons while injecting carriers by applying a voltage, resulting in a high luminance efficiency.

  12. The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells--new opportunities in regenerative medicine.

    Science.gov (United States)

    Marycz, Krzysztof; Śmieszek, Agnieszka; Jeleń, Marta; Chrząstek, Klaudia; Grzesiak, Jakub; Meissner, Justyna

    2015-09-01

    Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) belong to a family of bioactive sphingolipids that act as important extracellular signaling molecules and chemoattractants. This study investigated the influence of S1P and C1P on the morphology, proliferation activity and osteogenic properties of rat multipotent stromal cells derived from bone marrow (BMSCs) and subcutaneous adipose tissue (ASCs). We show that S1P and C1P can influence mesenchymal stem cells (MSCs), each in a different manner. S1P stimulation promoted the formation of cellular aggregates of BMSCs and ASCs, while C1P had an effect on the regular growth pattern and expanded intercellular connections, thereby increasing the proliferative activity. Although osteogenic differentiation of MSCs was enhanced by the addition of S1P, the effectiveness of osteoblast differentiation was more evident in BMSCs, particularly when biochemical and molecular marker levels were considered. The results of the functional osteogenic differentiation assay, which includes an evaluation of the efficiency of extracellular matrix mineralization (SEM-EDX), revealed the formation of numerous mineral aggregates in BMSC cultures stimulated with S1P. Our data demonstrated that in an appropriate combination, the bioactive sphingolipids S1P and C1P may find wide application in regenerative medicine, particularly in bone regeneration with the use of MSCs.

  13. A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders

    Science.gov (United States)

    Huwiler, Andrea; Bourquin, Florence; Kotelevets, Nataliya; Pastukhov, Oleksandr; Capitani, Guido; Grütter, Markus G.; Zangemeister-Wittke, Uwe

    2011-01-01

    Sphingosine-1-phosphate (S1P) regulates a broad spectrum of fundamental cellular processes like proliferation, death, migration and cytokine production. Therefore, elevated levels of S1P may be causal to various pathologic conditions including cancer, fibrosis, inflammation, autoimmune diseases and aberrant angiogenesis. Here we report that S1P lyase from the prokaryote Symbiobacterium thermophilum (StSPL) degrades extracellular S1P in vitro and in blood. Moreover, we investigated its effect on cellular responses typical of fibrosis, cancer and aberrant angiogenesis using renal mesangial cells, endothelial cells, breast (MCF-7) and colon (HCT 116) carcinoma cells as disease models. In all cell types, wild-type StSPL, but not an inactive mutant, disrupted MAPK phosphorylation stimulated by exogenous S1P. Functionally, disruption of S1P receptor signaling by S1P depletion inhibited proliferation and expression of connective tissue growth factor in mesangial cells, proliferation, migration and VEGF expression in carcinoma cells, and proliferation and migration of endothelial cells. Upon intravenous injection of StSPL in mice, plasma S1P levels rapidly declined by 70% within 1 h and then recovered to normal 6 h after injection. Using the chicken chorioallantoic membrane model we further demonstrate that also under in vivo conditions StSPL, but not the inactive mutant, inhibited tumor cell-induced angiogenesis as an S1P-dependent process. Our data demonstrate that recombinant StSPL is active under extracellular conditions and holds promise as a new enzyme therapeutic for diseases associated with increased levels of S1P and S1P receptor signaling. PMID:21829623

  14. Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors--an assessment of the efficacy of testing in donor screening. The HIV-Antigen Study Group.

    Science.gov (United States)

    Alter, H J; Epstein, J S; Swenson, S G; VanRaden, M J; Ward, J W; Kaslow, R A; Menitove, J E; Klein, H G; Sandler, S G; Sayers, M H

    1990-11-08

    We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three of the antigen-positive donors had other markers of infectious disease that would have resulted in the exclusion of their blood; two had risk factors for HIV-1 that should have led to self-exclusion. Of 220 blood units with repeatedly reactive p24 antigen whose presence could not be confirmed by neutralization (0.04 percent of the donations studied), none were positive for HIV-1 antibody, HIV-1 by polymerase chain reaction (120 units tested), or virus culture (76 units tested)--attesting to the specificity of confirmatory neutralization. The finding that no donation studied was positive for p24 antigen and negative for HIV-1 antibody suggests that screening donors for p24 antigen with tests of the current level of sensitivity would not add substantially to the safety of the U.S. blood supply.

  15. Formal Test Automation: The Conference Protocol with PHACT

    NARCIS (Netherlands)

    Heerink, A.W.; Ural, Hasan; Probert, Robert L.; Feenstra, J.; Tretmans, G.J.; von Bochmann, Gregor

    2000-01-01

    We discuss a case study of automatic test generation and test execution based on formal methods. The case is the Conference Protocol, a simple, chatbox-like protocol, for which (formal) specifications and multiple implementations are publicly available and which is also used in other case study

  16. CSF Aβ1-42, but not p-Tau181, differentiates aMCI from SCI.

    Science.gov (United States)

    Rizzi, Liara; Maria Portal, Marcelle; Batista, Carlos Eduardo Alves; Missiaggia, Luciane; Roriz-Cruz, Matheus

    2018-01-01

    Individuals with amnestic mild cognitive impairment (aMCI) are at a high risk to develop Alzheimer's disease (AD). We compared CSF levels of biomarkers of amyloidosis (Aβ 1-42 ) and neurodegeneration (p-Tau 181 ) in individuals with aMCI and with subjective cognitive impairment (SCI) in order to ascertain diagnostic accuracy and predict the odds ratio associated with aMCI. We collected CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory clinic of Southern Brazil. Levels of Aβ 1-42 and p-Tau 181 were measured by immunoenzymatic assay. Participants also underwent neuropsychological testing including the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimer's Disease (VM-CERAD). CSF concentration of Aβ 1-42 was significantly lower (p: .007) and p-Tau 181 /Aβ 1-42 ratio higher (p: .014) in aMCI individuals than in SCI. However, isolate p-Tau 181 levels were not associated with aMCI (p: .166). There was a statistically significant association between Aβ 1-42 and p-Tau 181 (R 2 : 0.177; β: -4.43; p: .017). ROC AUC of CSF Aβ 1-42 was 0.768 and of the p-Tau 181 /Aβ 1-42 ratio equals 0.742. Individuals with Aβ 1-42   0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy. VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CSF Aβ 1-42 , but not p-Tau 181, level was significantly associated with aMCI. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Ocean Optics Protocols for Satellite Ocean Color Sensor Validation. Volume 1; Revised

    Science.gov (United States)

    Mueller, James L. (Editor); Fargion, Giulietta (Editor); Mueller, J. L.; Trees, C.; Austin, R. W.; Pietras, C.; Hooker, S.; Holben, B.; McClain, Charles R.; Clark, D. K.; hide

    2002-01-01

    This document stipulates protocols for measuring bio-optical and radiometric data for the SIMBIOS Project. It supersedes the earlier version, and is organized into four parts: Introductory Background, Instrument Characteristics, Field Measurements and Data Analysis, Data Reporting and Archival. Changes in this revision include the addition of three new chapters: (1) Fundamental Definitions, Relationships and Conventions; (2) MOBY, A Radiometric Buoy for Performance Monitoring and Vicarious Calibration of Satellite Ocean Color Sensors: Measurement and Data Analysis Protocols; and (3) Normalized Water-Leaving Radiance and Remote Sensing Reflectance: Bidirectional Reflectance and Other Factors. Although the present document represents another significant, incremental improvement in the ocean optics protocols, there are several protocols that have either been overtaken by recent technological progress, or have been otherwise identified as inadequate. Revision 4 is scheduled for completion sometime in 2003. This technical report is not meant as a substitute for scientific literature. Instead, it will provide a ready and responsive vehicle for the multitude of technical reports issued by an operational Project. The contributions are published as submitted, after only minor editing to correct obvious grammatical or clerical errors.

  18. Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent.

    Science.gov (United States)

    Nisar, Shaista; Kelly, Eamonn; Cullen, Pete J; Mundell, Stuart J

    2010-04-01

    The activity and traffic of G-protein coupled receptors (GPCRs) is tightly controlled. Recent work from our laboratory has shown that P2Y(1) and P2Y(12) responsiveness is rapidly and reversibly modulated in human platelets and that the underlying mechanism requires receptor trafficking as an essential part of this process. However, little is known about the molecular mechanisms underlying P2Y receptor traffic. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. These functions may in part be due to interactions of SNX1 with the mammalian retromer complex. In this study, we investigated the role of SNX1 in P2Y receptor trafficking. We show that P2Y(1) receptors recycle via a slow recycling pathway that is regulated by SNX1, whereas P2Y(12) receptors return to the cell surface via a rapid route that is SNX1 independent. SNX1 inhibition caused a dramatic increase in the rate of P2Y(1) receptor recycling, whereas inhibition of Vps26 and Vps35 known to be present in retromer had no effect, indicating that SNX1 regulation of P2Y(1) receptor recycling is retromer independent. In addition, inhibition of SNX4, 6 and 17 proteins did not affect P2Y(1) receptor recycling. SNX1 has also been implicated in GPCR degradation; however, we provide evidence that P2Y receptor degradation is SNX1 independent. These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of GPCRs.

  19. A model based security testing method for protocol implementation.

    Science.gov (United States)

    Fu, Yu Long; Xin, Xiao Long

    2014-01-01

    The security of protocol implementation is important and hard to be verified. Since the penetration testing is usually based on the experience of the security tester and the specific protocol specifications, a formal and automatic verification method is always required. In this paper, we propose an extended model of IOLTS to describe the legal roles and intruders of security protocol implementations, and then combine them together to generate the suitable test cases to verify the security of protocol implementation.

  20. Assessing health systems for type 1 diabetes in sub-Saharan Africa: developing a 'Rapid Assessment Protocol for Insulin Access'

    Directory of Open Access Journals (Sweden)

    de Courten Maximilian

    2006-02-01

    Full Text Available Abstract Background In order to improve the health of people with Type 1 diabetes in developing countries, a clear analysis of the constraints to insulin access and diabetes care is needed. We developed a Rapid Assessment Protocol for Insulin Access, comprising a series of questionnaires as well as a protocol for the gathering of other data through site visits, discussions, and document reviews. Methods The Rapid Assessment Protocol for Insulin Access draws on the principles of Rapid Assessment Protocols which have been developed and implemented in several different areas. This protocol was adapted through a thorough literature review on diabetes, chronic condition management and medicine supply in developing countries. A visit to three countries in sub-Saharan Africa and meetings with different experts in the field of diabetes helped refine the questionnaires. Following the development of the questionnaires these were tested with various people familiar with diabetes and/or healthcare in developing countries. The Protocol was piloted in Mozambique then refined and had two further iterations in Zambia and Mali. Translations of questionnaires were made into local languages when necessary, with back translation to ensure precision. Results In each country the protocol was implemented in 3 areas – the capital city, a large urban centre and a predominantly rural area and their respective surroundings. Interviews were carried out by local teams trained on how to use the tool. Data was then collected and entered into a database for analysis. Conclusion The Rapid Assessment Protocol for Insulin Access was developed to provide a situational analysis of Type 1 diabetes, in order to make recommendations to the national Ministries of Health and Diabetes Associations. It provided valuable information on patients' access to insulin, syringes, monitoring and care. It was thus able to sketch a picture of the health care system with regards to its ability to

  1. Effects of carbohydrate and caffeine ingestion on performance during a rugby union simulation protocol.

    Science.gov (United States)

    Roberts, Simon P; Stokes, Keith A; Trewartha, Grant; Doyle, Jenny; Hogben, Patrick; Thompson, Dylan

    2010-06-01

    In this study, we investigated the effect of ingesting carbohydrate alone or with caffeine on performance of a rugby union-specific shuttle running protocol. On three occasions, at least one week apart in a counterbalanced trial order, eight male rugby union forwards ingested either placebo or carbohydrate (1.2 g x kg(-1) body mass x h(-1)) before and during a rugby union-specific protocol, with pre-exercise caffeine ingestion (4 mg x kg(-1)) before one of the carbohydrate trials (carbohydrate + caffeine). The intermittent exercise protocol included walking, jogging, and cruising at pre-determined intensities, simulated contact events, a sustained high-intensity test of speed and agility (Performance Test), and a 15-m sprint. Ratings of perceived exertion (RPE) were recorded every 5 min and a motor skills test was performed after each 21-min block. Performance Test times were not significantly different between trials but the likelihood of 2% improvements for carbohydrate + caffeine over placebo and carbohydrate were 98% and 44%, respectively. For carbohydrate + caffeine, 15-m sprints were faster than for placebo (P=0.05) and the motor skills test was performed faster in the carbohydrate + caffeine trial than the carbohydrate and placebo trials (P benefit to rugby performance following co-ingestion of carbohydrate and caffeine.

  2. Effect of i.p. insulin administration onIGF1 and IGFBP1 in type1 diabetes

    NARCIS (Netherlands)

    van Dijk, P R; Logtenberg, S J J; Groenier, K H; Kleefstra, N; Bilo, H J G; Arnqvist, H J

    2014-01-01

    In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH-IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p.

  3. Audit protocol of compliance test on x-ray and interventional radiodiagnostic

    International Nuclear Information System (INIS)

    Endang Kunarsih; Fitria Sandra

    2011-01-01

    Testing protocol is a document that defined and implemented by the testing agency in conducting compliance testing to ensure that quality of testing implementation is planned and controlled in accordance with applicable regulations and standards. Testing protocol is required in filing an application to be a qualified testing agency. Auditors will review the testing protocol document to assess adequacy of the acceptance criteria before proceed to the next process. This paper presents the acceptance criteria required in an audit of the testing protocol document from the applicant of testing agency. (author)

  4. Maternal obesity alters feto-placental Cytochrome P4501A1 activity

    Science.gov (United States)

    DuBois, Barent N.; O’Tierney, Perrie; Pearson, Jacob; Friedman, Jacob E.; Thornburg, Kent; Cherala, Ganesh

    2012-01-01

    Cytochrome P4501A1 (CYP1A1), an important drug metabolizing enzyme, is expressed in human placenta throughout gestation as well as in fetal liver. Obesity, a chronic inflammatory condition, is known to alter CYP enzyme expression in non-placental tissues. In the present study, we test the hypothesis that maternal obesity alters the distribution of CYP1A1 activity in feto-placental unit. Placentas were collected from non-obese (BMI30) women at term. Livers were collected from gestation day 130 fetuses of non-human primates fed either control diet or high-fat diet (HFD). Cytosol and microsomes were collected using differential centrifugation, and incubated with 7-Ethoxyresorufin. The CYP1A1 specific activity (pmoles of resorufin formed/min/mg of protein) was measured at excitation/emission wavelength of 530/590nm. Placentas of obese women had significantly reduced microsomal CYP1A1 activity compared to non-obese women (0.046 vs. 0.082; p<0.05); however no such effect was observed on cytosolic activity. Similarly, fetal liver from HFD fed mothers had significantly reduced microsomal CYP1A1 activity (0.44±0.04 vs. 0.20±0.10; p<0.05), with no significant difference in cytosolic CYP1A1 activity (control, 1.23±0.20; HFD, 0.80±0.40). Interestingly, multiple linear regression analyses of placental efficiency indicates cytosolic CYP1A1 activity is a main effect (5.67±2.32 (β±SEM); p=0.022) along with BMI (−0.57±0.26; p=0.037), fetal gender (1.07±0.26; p<0.001), and maternal age (0.07±0.03; p=0.011). In summary, while maternal obesity affects microsomal CYP1A1 activity alone, cytosolic activity along with maternal BMI is an important determinant of placental efficiency. Together, these data suggest that maternal lifestyle could have a significant impact on CYP1A1 activity, and hints at a possible role for CYP1A1 in feto-placental growth and thereby well-being of fetus. PMID:23046808

  5. Fiber Laser Component Testing for Space Qualification Protocol Development

    Science.gov (United States)

    Falvey, S.; Buelow, M.; Nelson, B.; Starcher, Y.; Thienel, L.; Rhodes, C.; Tull, Jackson; Drape, T.; Westfall, C.

    A test protocol for the space qualifying of Ytterbium-doped diode-pumped fiber laser (DPFL) components was developed under the Bright Light effort, sponsored by AFRL/VSE. A literature search was performed and summarized in an AMOS 2005 conference paper that formed the building blocks for the development of the test protocol. The test protocol was developed from the experience of the Bright Light team, the information in the literature search, and the results of a study of the Telcordia standards. Based on this protocol developed, test procedures and acceptance criteria for a series of vibration, thermal/vacuum, and radiation exposure tests were developed for selected fiber laser components. Northrop Grumman led the effort in vibration and thermal testing of these components at the Aerospace Engineering Facility on Kirtland Air Force Base, NM. The results of the tests conducted have been evaluated. This paper discusses the vibration and thermal testing that was executed to validate the test protocol. The lessons learned will aid in future assessments and definition of space qualification protocols. Components representative of major items within a Ytterbium-doped diode-pumped fiber laser were selected for testing; including fibers, isolators, combiners, fiber Bragg gratings, and laser diodes. Selection of the components was based on guidelines to test multiple models of typical fiber laser components. A goal of the effort was to test two models (i.e. different manufacturers) of each type of article selected, representing different technologies for the same type of device. The test articles did not include subsystems or systems. These components and parts may not be available commercial-off-the-shelf (COTS), and, in fact, many are custom articles, or newly developed by the manufacturer. The primary goal for this effort is a completed taxonomy that lists all relevant laser components, modules, subsystems, and interfaces, and cites the documentation for space

  6. Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Ruo-Chia Tseng

    2009-08-01

    Full Text Available A HIC1-SIRT1-p53 circular loop in which hypermethylation in cancer 1 (HIC1 represses the transcription of SIRT1 that deacetylates and inactivates p53 thus leading to HIC1 inactivation has been identified in cell and animal models. However, the alteration and prognostic effects of HIC1-SIRT1-p53 circular loop have never been demonstrated in human cancer patients. We examine the HIC1-SIRT1-p53 alterations in 118 lung cancer patients to define their etiological roles in tumorigenesis. We found that patients with lung squamous cell carcinoma with low p53 acetylation and SIRT1 expression mostly showed low HIC1 expression, confirming deregulation of HIC1-SIRT1-p53 circular loop in the clinical model. Interestingly, the expression of deleted in breast cancer 1 (DBC1, which blocks the interaction between SIRT1 deacetylase and p53, led to acetylated p53 in patients with lung adenocarcinoma. However, epigenetic alteration of HIC1 promoter by posttranslational modifications of histones and promoter hypermethylation favoring the compacted chromatin production attenuated the transcriptional induction by acetylated p53. Importantly, lung cancer patients with altered HIC1-SIRT1-p53 circular regulation showed poor prognosis. Our data show the first valid clinical evidence of the deregulation of HIC1-SIRT1-p53 loop in lung tumorigenesis and prognosis. Distinct status of p53 acetylation/deacetylation and HIC1 alteration mechanism result from different SIRT1-DBC1 control and epigenetic alteration in lung squamous cell carcinoma and lung adenocarcinoma.

  7. Differential Recognition of Old World and New World Arenavirus Envelope Glycoproteins by Subtilisin Kexin Isozyme 1 (SKI-1)/Site 1 Protease (S1P)

    Science.gov (United States)

    Burri, Dominique J.; Ramos da Palma, Joel; Seidah, Nabil G.; Zanotti, Giuseppe; Cendron, Laura

    2013-01-01

    The arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). Comparison of the currently known sequences of arenavirus GPCs revealed the presence of a highly conserved aromatic residue at position P7 relative to the SKI-1/S1P cleavage side in Old World and clade C New World arenaviruses but not in New World viruses of clades A and B or cellular substrates of SKI-1/S1P. Using a combination of molecular modeling and structure-function analysis, we found that residueY285 of SKI-1/S1P, distal from the catalytic triad, is implicated in the molecular recognition of the aromatic “signature residue” at P7 in the GPC of Old World Lassa virus. Using a quantitative biochemical approach, we show that Y285 of SKI-1/S1P is crucial for the efficient processing of peptides derived from Old World and clade C New World arenavirus GPCs but not of those from clade A and B New World arenavirus GPCs. The data suggest that during coevolution with their mammalian hosts, GPCs of Old World and clade C New World viruses expanded the molecular contacts with SKI-1/S1P beyond the classical four-amino-acid recognition sequences and currently occupy an extended binding pocket. PMID:23536681

  8. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

    Directory of Open Access Journals (Sweden)

    Xiao-Su Zhao

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  9. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

    Science.gov (United States)

    Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  10. A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes

    International Nuclear Information System (INIS)

    Hondow, Heather L; Fox, Stephen B; Mitchell, Gillian; Scott, Rodney J; Beshay, Victoria; Wong, Stephen Q; Dobrovic, Alexander

    2011-01-01

    Detection of mutations by DNA sequencing can be facilitated by scanning methods to identify amplicons which may have mutations. Current scanning methods used for the detection of germline sequence variants are laborious as they require post-PCR manipulation. High resolution melting (HRM) is a cost-effective rapid screening strategy, which readily detects heterozygous variants by melting curve analysis of PCR products. It is well suited to screening genes such as BRCA1 and BRCA2 as germline pathogenic mutations in these genes are always heterozygous. Assays for the analysis of all coding regions and intron-exon boundaries of BRCA1 and BRCA2 were designed, and optimised. A final set of 94 assays which ran under identical amplification conditions were chosen for BRCA1 (36) and BRCA2 (58). Significant attention was placed on primer design to enable reproducible detection of mutations within the amplicon while minimising unnecessary detection of polymorphisms. Deoxyinosine residues were incorporated into primers that overlay intronic polymorphisms. Multiple 384 well plates were used to facilitate high throughput. 169 BRCA1 and 239 BRCA2 known sequence variants were used to test the amplicons. We also performed an extensive blinded validation of the protocol with 384 separate patient DNAs. All heterozygous variants were detected with the optimised assays. This is the first HRM approach to screen the entire coding region of the BRCA1 and BRCA2 genes using one set of reaction conditions in a multi plate 384 well format using specifically designed primers. The parallel screening of a relatively large number of samples enables better detection of sequence variants. HRM has the advantages of decreasing the necessary sequencing by more than 90%. This markedly reduced cost of sequencing will result in BRCA1 and BRCA2 mutation testing becoming accessible to individuals who currently do not undergo mutation testing because of the significant costs involved

  11. Compound list: transforming growth factor beta 1 [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available transforming growth factor beta 1 TGFB1 00182 ftp://ftp.biosciencedbc.jp/archive/op...en-tggates/LATEST/Human/in_vitro/transforming_growth_factor_beta_1.Human.in_vitro.Liver.zip ...

  12. Electron impact excitation-autoionisation of the (2s2)1S, (2p2)1D and (2s2p)1P autoionising states of helium

    International Nuclear Information System (INIS)

    Samardzic, O.; Hurn, J.A.; Weigold, E.; Brunger, M.J.

    1994-01-01

    The electron impact excitation of the (2s 2 ) 1 S, (2p 2 ) 1 D and (2s2p) 1 P autoionising states of helium and their subsequent radiationless decay was studied by observation of the ejected electrons. The present work was carried out at an incident energy of 94.6 eV and for ejected electron scattering angles in the range 25-135 deg C. The lineshapes observed in the present ejected electron spectra are analysed using the Shore-Balashov parametrisation. As part of the analysis procedure, numerically rigorous confidence limits were determined for the derived parameters. No previous experimental or theoretical work has been undertaken at the incident energy of the present investigation but, where possible, the resulting parameters are qualitatively compared against the 80 eV results of other experiments and theory. 37 refs., 4 figs

  13. Modeling Tolerance Development for the Effect on Heart Rate of the Selective S1P1 Receptor Modulator Ponesimod.

    Science.gov (United States)

    Lott, Dominik; Lehr, Thorsten; Dingemanse, Jasper; Krause, Andreas

    2017-09-15

    Ponesimod is a selective sphingosine-1-phosphate-1 (S1P 1 ) receptor modulator currently under investigation for the treatment of multiple sclerosis. S1P receptor modulators reduce heart rate following treatment initiation. This effect disappears with repeated dosing, enabling development of innovative uptitration regimens to optimize patient safety. There are currently no published pharmacokinetic/pharmacodynamic models describing the heart rate reduction of S1P receptor modulators in humans. The model developed here provides quantification of this effect for ponesimod. A direct-effect I max model with estimated maximum reduction of 45%, tolerance development, and circadian variation best described this effect. The pooled data from nine clinical studies enabled characterization of interindividual variability. The model was used to simulate different treatment regimens to compare the effect of high initial doses vs. gradual uptitration with respect to the occurrence of bradycardia. The results indicate a better safety profile when using gradual uptitration. The model allows studying dosing regimens not clinically tested in silico. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  14. UVB-induced gene expression in the skin of Xiphophorus maculatus Jp 163 B☆

    Science.gov (United States)

    Yang, Kuan; Boswell, Mikki; Walter, Dylan J.; Downs, Kevin P.; Gaston-Pravia, Kimberly; Garcia, Tzintzuni; Shen, Yingjia; Mitchell, David L.; Walter, Ronald B.

    2014-01-01

    Xiphophorus fish and interspecies hybrids represent long-standing models to study the genetics underlying spontaneous and induced tumorigenesis. The recent release of the Xiphophorus maculatus genome sequence will allow global genetic regulation studies of genes involved in the inherited susceptibility to UVB-induced melanoma within select backcross hybrids. As a first step toward this goal, we report results of an RNA-Seq approach to identify genes and pathways showing modulated transcription within the skin of X. maculatus Jp 163 B upon UVB exposure. X. maculatus Jp 163 B were exposed to various doses of UVB followed by RNA-Seq analysis at each dose to investigate overall gene expression in each sample. A total of 357 genes with a minimum expression change of 4-fold (p-adj fish skin to UVB exposure. PMID:24556253

  15. Post-test analysis of PANDA test P4

    International Nuclear Information System (INIS)

    Hart, J.; Woudstra, A.; Koning, H.

    1999-01-01

    The results of a post-test analysis of the integral system test P4, which has been executed in the PANDA facility at PSI in Switzerland within the framework of Work Package 2 of the TEPSS project are presented. The post-test analysis comprises an evaluation of the PANDA test P4 and a comparison of the test results with the results of simulations using the RELAPS/MOD3.2, TRAC-BF1, and MELCOR 1.8.4 codes. The PANDA test P4 has provided data about how trapped air released from the drywell later in the transient affects PCCS performance in an adequate manner. The well-defined measurements can serve as an important database for the assessment of thermal hydraulic system analysis codes, especially for conditions that could be met in passively operated advanced reactors, i.e. low pressure and small driving forces. Based on the analysis of the test data, the test acceptance criteria have been met. The test P4 has been successfully completed and the instrument readings were with the permitted ranges. The PCCs showed a favorable and robust performance and a wide margin for decay heat removal from the containment. The PANDA P4 test demonstrated that trapped air, released from the drywell later in the transient, only temporarily and only slightly affected the performance of the passive containment cooling system. The analysis of the results of the RELAPS code showed that the overall behaviour of the test has been calculated quite well with regards to pressure, mass flow rates, and pool boil-down. This accounts both for the pre-test and the post-test simulations. However, due to the one-dimensional, stacked-volume modeling of the PANDA DW, WW, and GDCS vessels, 3D-effects such as in-vessel mixing and recirculation could not be calculated. The post-test MELCOR simulation showed an overall behaviour that is comparable to RELAPS. However, MELCOR calculated almost no air trapping in the PCC tubes that could hinder the steam condensation rate. This resulted in lower calculated

  16. Transcriptional regulation of the p73 gene, a member of the p53 family, by early growth response-1 (Egr-1)

    International Nuclear Information System (INIS)

    Lee, Sang-Wang; Kim, Eun-Joo; Um, Soo-Jong

    2007-01-01

    To elucidate the regulatory mechanism of p73 gene expression, we analyzed the human p73 promoter and found three putative Egr-1-binding sites located upstream of exon 1 (-1728, -321, and -38). The Egr-1 responsiveness of these sites was analyzed by transient transfection assays using 5'- and 3'-serial truncations of the p73 promoter, subcloned in a CAT reporter vector. The functional significance of the region was further confirmed by an electrophoretic mobility shift assay using the Egr-1 protein synthesized in vitro and a [ 32 P]-labeled middle site sequence, followed by competition with unlabeled wild-type or mutant oligonucleotides and supershift assays using an anti-Egr-1 antibody. When induced by either the nitric oxide donor NOC-18 or the PPARγ agonist troglitazone, Egr-1 bound to the p73 promoter, as assessed by chromatin immunoprecipitation assays, accompanied by increased expression of p73. MTT assays revealed that cell growth was significantly inhibited on treating the cells with troglitazone. Overall, our results provide direct evidence that Egr-1 positively regulated p73 expression by binding to its promoter in vivo, consistent with Egr-1 and p73 being involved in p53-independent tumor suppression

  17. Optimizing the high-resolution manometry (HRM) study protocol.

    Science.gov (United States)

    Patel, A; Ding, A; Mirza, F; Gyawali, C P

    2015-02-01

    Intolerance of the esophageal manometry catheter may prolong high-resolution manometry (HRM) studies and increase patient distress. We assessed the impact of obtaining the landmark phase at the end of the study when the patient has acclimatized to the HRM catheter. 366 patients (mean age 55.4 ± 0.8 years, 62.0% female) undergoing esophageal HRM over a 1-year period were studied. The standard protocol consisted of the landmark phase, 10 5 mL water swallows 20-30 s apart, and multiple rapid swallows where 4-6 2 mL swallows were administered in rapid succession. The modified protocol consisted of the landmark phase at the end of the study after test swallows. Study duration, technical characteristics, indications, and motor findings were compared between standard and modified protocols. Of the 366 patients, 89.6% underwent the standard protocol (study duration 12.9 ± 0.3 min). In 10.4% with poor catheter tolerance undergoing the modified protocol, study duration was significantly longer (15.6 ± 1.0 min, p = 0.004) despite similar duration of study maneuvers. Only elevated upper esophageal sphincter basal pressures at the beginning of the study segregated modified protocol patients. The 95th percentile time to landmark phase in the standard protocol patients was 6.1 min; as many as 31.4% of modified protocol patients could not obtain their first study maneuver within this period (p = 0.0003). Interpretation was not impacted by shifting the landmark phase to the end of the study. Modification of the HRM study protocol with the landmark phase obtained at the end of the study optimizes study duration without compromising quality. © 2014 John Wiley & Sons Ltd.

  18. Improved wavelengths for the 1s2s3S1-1s2p3P0,2 transitions in helium-like Si12+

    International Nuclear Information System (INIS)

    Armour, I.A.; Myers, E.G.; Silver, J.D.; Traebert, E.; Oxford Univ.

    1979-01-01

    The wavelengths of the 1s2s 3 S 1 -1s2p 3 P 0 , 2 transitions in He-like Si 12+ have been remaesured to be 87.86 +- 0.01 nm and 81.48 +- 0.01 nm. The use of Rydberg lines for the calibration of fast beam spectra is discussed. (orig.)

  19. Lysine-specific demethylase 1 (LSD1) destabilizes p62 and inhibits autophagy in gynecologic malignancies.

    Science.gov (United States)

    Chao, Angel; Lin, Chiao-Yun; Chao, An-Ning; Tsai, Chia-Lung; Chen, Ming-Yu; Lee, Li-Yu; Chang, Ting-Chang; Wang, Tzu-Hao; Lai, Chyong-Huey; Wang, Hsin-Shih

    2017-09-26

    Lysine-specific demethylase 1 (LSD1) - also known as KDM1A - is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 - also termed sequestasome 1 (SQSTM1) - plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo . The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

  20. Cytochrome P450 1A1 (CYP1A1) protects against nonalcoholic fatty liver disease caused by Western diet containing benzo[a]pyrene in mice.

    Science.gov (United States)

    Uno, Shigeyuki; Nebert, Daniel W; Makishima, Makoto

    2018-03-01

    The Western diet contributes to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Benzo[a]pyrene (BaP), a prototypical environmental pollutant produced by combustion processes, is present in charcoal-grilled meat. Cytochrome P450 1A1 (CYP1A1) metabolizes BaP, resulting in either detoxication or metabolic activation in a context-dependent manner. To elucidate a role of CYP1A1-BaP in NAFLD pathogenesis, we compared the effects of a Western diet, with or without oral BaP treatment, on the development of NAFLD in Cyp1a1(-/-) mice versus wild-type mice. A Western diet plus BaP induced lipid-droplet accumulation in liver of Cyp1a1(-/-) mice, but not wild-type mice. The hepatic steatosis observed in Cyp1a1(-/-) mice was associated with increased cholesterol, triglyceride and bile acid levels. Cyp1a1(-/-) mice fed Western diet plus BaP had changes in expression of genes involved in bile acid and lipid metabolism, and showed no increase in Cyp1a2 expression but did exhibit enhanced Cyp1b1 mRNA expression, as well as hepatic inflammation. Enhanced BaP metabolic activation, oxidative stress and inflammation may exacerbate metabolic dysfunction in liver of Cyp1a1(-/-) mice. Thus, Western diet plus BaP induces NAFLD and hepatic inflammation in Cyp1a1(-/-) mice in comparison to wild-type mice, indicating a protective role of CYP1A1 against NAFLD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia.

    Science.gov (United States)

    Li, Qinghua; Pan, Zhifang; Wang, Xuejian; Gao, Zhiqin; Ren, Chune; Yang, Weiwei

    2014-10-10

    Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Deficiency of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 accelerates atherogenesis in apolipoprotein E-deficient mice

    International Nuclear Information System (INIS)

    Akyuerek, Levent M.; Boehm, Manfred; Olive, Michelle; Zhou, Alex-Xianghua; San, Hong; Nabel, Elizabeth G.

    2010-01-01

    Cyclin-dependent kinase inhibitors, p21 Cip1 and p27 Kip1 , are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21 Cip1 or p27 Kip1 in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE -/- aortae, both apoE -/- /p21 -/- and apoE -/- /p27 -/- aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27 Kip1 accelerated plaque formation significantly more than p21 -/- in apoE -/- mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21 Cip1 and p27 Kip1 accelerates atherogenesis in apoE -/- mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.

  3. REMOTE SENSING OF CH4 BY COMBINING LIDAR AND OPTICAL CORRELATION SPECTROSCOPY : FIRST EXPERIMENTAL RESULTS B. Thomas1, A. Miffre1, G. David1, J.P. Cariou2, P. Rairoux1 1Laboratoire de Spectrométrie Ionique et Moléculaire, CNRS, UMR 5579 Université Lyon 1, 10 rue Ada Byron, 69622 Villeurbanne, France, patrick.rairoux@univ-lyon1.fr 2Leosphere France, 14-16 rue Jean Rostand, 91400 Orsay, France, jpcariou@leosphere.fr

    Science.gov (United States)

    Thomas, B.; Miffre, A.; David, G.; Cariou, J.; Rairoux, P.

    2012-12-01

    In this contribution, we present a new methodology, called OCS-lidar, to remotely evaluate trace gas concentrations in the atmosphere (B. Thomas et al, 2012), as well as the first methane concentration measurements using this methodology. It is based on combining the Optical Correlation Spectroscopy (OCS) method with laser remote sensing technique (lidar). As displayed on figure 1, an Acoustic Optical Programmable Dispersive Filter is coupled with spectrally broadened femtosecond laser pulses to achieve the optical correlation between the emitted laser pulse and the methane absorption cross-section. In a first time, statistical and systematical errors of the OCS-lidar methodology have been evaluated thanks to a numerical model. The detection noise, interfering trace gases, temperature and pressure variations as well as laser pulse-to-pulse fluctuations have been considered. OCS-lidar simulations for methane concentration measurements have been achieved for background concentration (1.5 to 3 ppm), low (tens of ppm) and high sources (hundreds of ppm). Results show that background measurements are possible in the hour range while sources assessment and localization can be achieved in 10 minutes range up to 3 km range. Then, first methane concentration experimental measurements by using the OCS-lidar methodology will be presented. The laser source is an Oscillator Parametric Amplifier with emitting wavelength from 1.1 to 2 μm with 0.2 mJ at 1 kHz repetition rate. An AOPDF is used to generate correlated and non-correlated (or reference) signal. Experimental results on background methane concentration and on remote point source measurements will be presented, showing the achieved sensitivity and accuracy in both geophysical conditions.igure 1. Scheme of the OCS-Lidar principle. A broadened laser source centered on λ0-wavelength, with power spectral density P0, is used to create spectrally shaped power density P0M1 and P0M2, which are respectively correlated and anti

  4. Financial incentive does not affect P300 (in response to certain episodic and semantic probe stimuli) in the Complex Trial Protocol (CTP) version of the Concealed Information Test (CIT) in detection of malingering.

    Science.gov (United States)

    Rosenfeld, J Peter; Labkovsky, Elena; Davydova, Elena; Ward, Anne; Rosenfeld, Lauren

    2017-05-01

    Previous research indicated that the skin conductance response of the autonomic nervous system in the Concealed Information Test (CIT) is typically increased in subjects who are financially and otherwise incentivized to defeat the CIT (the paradoxical "motivational impairment" effect). This is not the case for RT-based CITs, nor P300 tests based on the three-stimulus protocol for detection of cognitive malingering (although these are not the same as CITs). The present report is the first attempt to study the effect of financial motivation on the P300-based Complex Trial Protocol using both episodic and semantic memory probe and irrelevant stimuli. The Test of Memory Malingering (TOMM) was used to validate behavioral differences between the two groups we created by offering one (paid) group but not another (unpaid) group a financial reward for beating our tests. Group behavioral differences on the TOMM did confirm group manipulations. Probe-minus-irrelevant P300 differences did not differ between groups, although as previously, semantic memory-evoked P300s were larger than episodic memory-evoked P300s. © 2017 Society for Psychophysiological Research.

  5. Use of a standardized JaCVAM in vivo rat comet assay protocol to assess the genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2-dimethylhydrazine dihydrochloride, and N-nitrosodimethylamine.

    Science.gov (United States)

    McNamee, J P; Bellier, P V

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), our laboratory examined ampicillin trihydrate (AMP), 1,2-dimethylhydrazine dihydrochloride (DMH), and N-nitrosodimethylamine (NDA) using a standard comet assay validation protocol (v14.2) developed by the JaCVAM validation management team (VMT). Coded samples were received by our laboratory along with basic MSDS information. Solubility analysis and range-finding experiments of the coded test compounds were conducted for dose selection. Animal dosing schedules, the comet assay processing and analysis, and statistical analysis were conducted in accordance with the standard protocol. Based upon our blinded evaluation, AMP was not found to exhibit evidence of genotoxicity in either the rat liver or stomach. However, both NDA and DMH were observed to cause a significant increase in % tail DNA in the rat liver at all dose levels tested. While acute hepatoxicity was observed for these compounds in the high dose group, in the investigators opinion there were a sufficient number of consistently damaged/measurable cells at the medium and low dose groups to judge these compounds as genotoxic. There was no evidence of genotoxicity from either NDA or DMH in the rat stomach. In conclusion, our laboratory observed increased DNA damage from two blinded test compounds in rat liver (later identified as genotoxic carcinogens), while no evidence of genotoxicity was observed for the third blinded test compound (later identified as a non-genotoxic, non-carcinogen). This data supports the use of a standardized protocol of the in vivo comet assay as a cost-effective alternative genotoxicity assay for regulatory testing purposes. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  6. Optical properties of lattice matched InxGa1-xP1-yNy heteroepitaxial layers on GaP

    International Nuclear Information System (INIS)

    Imanishi, T.; Wakahara, A.; Kim, S.M.; Yonezu, H.; Furukawa, Y.

    2005-01-01

    Optical constants and band structure of In x Ga 1-x P 1-y N y lattice matched to GaP (100) substrate are investigated. Nitrogen concentration in the film estimated by X-ray diffraction and X-ray photoelectron spectroscopy, was 1.4%, 1.8% and 3.5%. Refractive index and transition critical points E 0 (Γ v to Γ c ), E 1 (L v to L c ) and E 2 (X v to X c ) are evaluated by spectroscopic ellipsometry. When N composition increases from 1.4% to 3.5%, both photoluminescence (PL) peak energy, E PL , and E 0 shift to lower energy, and the energy difference ΔE=E 0 -E PL decrease from 380 meV to 110 meV. The large red-sift of E PL from the E 0 suggest that the luminescence is of defect-related luminescence, and crossover point of indirect band structure estimated by the extrapolation of N-composition dependence of ΔE is estimated to be around in In 0.1 Ga 0.9 P 0.96 N 0.04 . (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. Moderate financial incentive does not appear to influence the P300 Concealed Information Test (CIT) effect in the Complex Trial Protocol (CTP) version of the CIT in a forensic scenario, while affecting P300 peak latencies and behavior.

    Science.gov (United States)

    Rosenfeld, J Peter; Sitar, Evan; Wasserman, Joshua; Ward, Anne

    2018-03-01

    Previous research indicated that the skin conductance response (SCR) of the Autonomic Nervous System (ANS) in the Concealed Information Test (CIT) is typically increased in subjects who are financially and otherwise incentivized to defeat the CIT (the paradoxical "motivational impairment" effect). This is not the case for RT-based CITs, nor for P300 tests based on the 3-stimulus protocol or Complex Trial Protocol for detection of cognitive malingering (although these are not the same as forensic CITs). The present report extends earlier studies of malingerers by running five groups of subjects (15-16 per group yielding 78 total) in a mock crime (forensic) scenario: paid (to beat the test) and unpaid, instructed and uninstructed, and simply guilty. There was no evidence that the "CIT effect" (probe-minus-irrelevant P300 differences) differed among groups, although behavioral differences among groups were seen. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

    Directory of Open Access Journals (Sweden)

    Giovanni Morelli

    2018-05-01

    Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

  9. Develop and Implement Operational Ground Testing Protocols to Individualize Astronaut Sleep Medication Efficacy and Individual Effects

    Data.gov (United States)

    National Aeronautics and Space Administration — The study protocol was successfully pilot tested with N=7 subjects (6 NASA flight surgeons and 1 Behavioral Health and Performance element Operations professional)...

  10. Only Acyl Carrier Protein 1 (AcpP1 Functions in Pseudomonas aeruginosa Fatty Acid Synthesis

    Directory of Open Access Journals (Sweden)

    Jin-Cheng Ma

    2017-11-01

    Full Text Available The genome of Pseudomonas aeruginosa contains three open reading frames, PA2966, PA1869, and PA3334, which encode putative acyl carrier proteins, AcpP1, AcpP2, and AcpP3, respectively. In this study, we found that, although these apo-ACPs were successfully phosphopantetheinylated by P. aeruginosa phosphopantetheinyl transferase (PcpS and all holo-forms of these proteins could be acylated by Vibrio harveyi acyl-ACP synthetase (AasS, only AcpP1 could be used as a substrate for the synthesis of fatty acids, catalyzed by P. aeruginosa cell free extracts in vitro, and only acpP1 gene could restore growth in the Escherichia coliacpP mutant strain CY1877. And P. aeruginosaacpP1 could not be deleted, while disruption of acpP2 or acpP3 in the P. aeruginosa genome allowed mutant strains to grow as well as the wild type strain. These findings confirmed that only P. aeruginosa AcpP1 functions in fatty acid biosynthesis, and that acpP2 and acpP3 do not play roles in the fatty acid synthetic pathway. Moreover, disruption of acpP2 and acpP3 did not affect the ability of P. aeruginosa to produce N-acylhomoserine lactones (AHL, but replacement of P. aeruginosaacpP1 with E. coliacpP caused P. aeruginosa to reduce the production of AHL molecules, which indicated that neither P. aeruginosa AcpP2 nor AcpP3 can act as a substrate for synthesis of AHL molecules in vivo. Furthermore, replacement of acpP1 with E. coliacpP reduced the ability of P. aeruginosa to produce some exo-products and abolished swarming motility in P. aeruginosa.

  11. Lipotoxicity induces hepatic protein inclusions through TBK1-mediated p62/SQSTM1 phosphorylation.

    Science.gov (United States)

    Cho, Chun-Seok; Park, Hwan-Woo; Ho, Allison; Semple, Ian A; Kim, Boyoung; Jang, Insook; Park, Haeli; Reilly, Shannon; Saltiel, Alan R; Lee, Jun Hee

    2017-12-18

    Obesity commonly leads to hepatic steatosis, which often provokes lipotoxic injuries to hepatocytes that cause non-alcoholic steatohepatitis (NASH). NASH in turn is associated with the accumulation of insoluble protein aggregates that are composed of ubiquitinated proteins and ubiquitin adaptor p62/sequestosome 1 (SQSTM1). The formation of p62 inclusions in hepatocytes is the critical marker that distinguishes simple fatty liver from NASH and predicts a poor prognostic outcome for subsequent liver carcinogenesis. However, the molecular mechanism by which lipotoxicity induces protein aggregation is currently unknown. Here we show that upon saturated fatty acid-induced lipotoxicity, Tank-binding protein kinase 1 (TBK1) is activated and phosphorylates p62. The TBK1-mediated p62 phosphorylation is important for lipotoxicity-induced aggregation of ubiquitinated proteins and the formation of large protein inclusions in hepatocytes. In addition, cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), upstream regulators of TBK1, are involved in the lipotoxic activation of TBK1 and subsequent p62 phosphorylation in hepatocytes. Furthermore, TBK1 inhibition prevented formation of the ubiquitin-p62 aggregates, not only in cultured hepatocytes, but also in mouse models of obesity and NASH. These results suggest that lipotoxic activation of TBK1 and subsequent p62 phosphorylation are critical steps in the NASH pathology of protein inclusion accumulation in hepatocytes. This mechanism can provide an explanation for how hypernutrition and obesity promote the development of severe liver pathologies, such as steatohepatitis and liver cancer, by facilitating the formation of p62 inclusions. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  12. Co-expression of human cytochrome P4501A1 (CYP1A1) variants and human NADPH-cytochrome P450 reductase in the baculovirus/insect cell system.

    Science.gov (United States)

    Schwarz, D; Kisselev, P; Honeck, H; Cascorbi, I; Schunck, W H; Roots, I

    2001-06-01

    1. Three human cytochrome P4501A1 (CYP1A1) variants, wild-type (CYP1A1.1), CYP1A1.2 (1462V) and CYP1A1.4 (T461N), were co-expressed with human NADPH-P450 reductase (OR) in Spodoptera frugiperda (Sf9) insect cells by baculovirus co-infection to elaborate a suitable system for studying the role of CYPA1 polymorphism in the metabolism of exogenous and endogenous substrates. 2. A wide range of conditions was examined to optimize co-expression with regard to such parameters as relative multiplicity of infection (MOI), time of harvest, haem precursor supplementation and post-translational stabilization. tinder optimized conditions, almost identical expression levels and molar OR/CYP1A1 ratios (20:1) were attained for all CYP1A1 variants. 3. Microsomes isolated from co-infected cells demonstrated ethoxyresorufin deethlylase activities (nmol/min(-1) nmol(-1) CYP1A1) of 16.0 (CYP1A1.1), 20.5 (CYP1A1.2) and 22.5 (CYP1A1.4). Pentoxyresorufin was dealkylated approximately 10-20 times slower with all enzyme variants. 4. All three CYP1A1 variants were active in metabolizing the precarcinogen benzo[a]pyrene (B[a]P), with wild-type enzyme showing the highest activity, followed by CYP1A1.4 (60%) and CYP1A1.2 (40%). Each variant produced all major metabolites including B[a]P-7,8-dihydrodiol, the precursor of the ultimate carcinogenic species. 5. These studies demonstrate that the baculovirus-mediated co-expression-by-co-infection approach all CYP1A1 variants yields functionally active enzyme systems with similar molar OR/CYP1A1 ratios, thus providing suitable preconditions to examine the metabolism of and environmental chemicals by the different CY1A1 variants.

  13. FLOW TESTING AND ANALYSIS OF THE FSP-1 EXPERIMENT

    Energy Technology Data Exchange (ETDEWEB)

    Hawkes, Grant L.; Jones, Warren F.; Marcum, Wade; Weiss, Aaron; Howard, Trevor

    2017-06-01

    The U.S. High Performance Research Reactor Conversions fuel development team is focused on developing and qualifying the uranium-molybdenum (U-Mo) alloy monolithic fuel to support conversion of domestic research reactors to low enriched uranium. Several previous irradiations have demonstrated the favorable behavior of the monolithic fuel. The Full Scale Plate 1 (FSP-1) fuel plate experiment will be irradiated in the northeast (NE) flux trap of the Advanced Test Reactor (ATR). This fueled experiment contains six aluminum-clad fuel plates consisting of monolithic U-Mo fuel meat. Flow testing experimentation and hydraulic analysis have been performed on the FSP-1 experiment to be irradiated in the ATR at the Idaho National Laboratory (INL). A flow test experiment mockup of the FSP-1 experiment was completed at Oregon State University. Results of several flow test experiments are compared with analyses. This paper reports and shows hydraulic analyses are nearly identical to the flow test results. A water velocity of 14.0 meters per second is targeted between the fuel plates. Comparisons between FSP-1 measurements and this target will be discussed. This flow rate dominates the flow characteristics of the experiment and model. Separate branch flows have minimal effect on the overall experiment. A square flow orifice was placed to control the flowrate through the experiment. Four different orifices were tested. A flow versus delta P curve for each orifice is reported herein. Fuel plates with depleted uranium in the fuel meat zone were used in one of the flow tests. This test was performed to evaluate flow test vibration with actual fuel meat densities and reported herein. Fuel plate deformation tests were also performed and reported.

  14. Soft chelating irrigation protocol optimizes bonding quality of Resilon/Epiphany root fillings.

    Science.gov (United States)

    De-Deus, Gustavo; Namen, Fátima; Galan, João; Zehnder, Matthias

    2008-06-01

    This study was designed to test the impact of either a strong (MTAD) or a soft (1-hydroxyethylidene-1, 1-bisphosphonate [HEPB]) chelating solution on the bond strength of Resilon/Epiphany root fillings. Both 17% EDTA and the omission of a chelator in the irrigation protocol were used as reference treatments. Forty extracted human upper lateral incisors were prepared using different irrigation protocols (n = 10): G1: NaOCl, G2: NaOCl + 17% EDTA, G3: NaOCl + BioPure MTAD (Dentsply/Tulsa, Tulsa, OK), and G4: NaOCl + 18% HEPB. The teeth were obturated and then prepared for micropush-out assessment using root slices of 1 mm thickness. Loading was performed on a universal testing machine at a speed of 0.5 mm/min. One-way analysis of variance and Tukey multiple comparisons were used to compare the results among the experimental groups. EDTA- and MTAD-treated samples revealed intermediate bond strength (0.3-3.6 MPa). The lowest bond strengths were achieved in NaOCl-treated samples (0.3-1.2 MPa, p < 0.05). The highest bond strength was reached in the HEBP-treated samples (3.1-6.1 MPa, p < 0.05). Under the present in vitro conditions, the soft chelating irrigation protocol (18% HEBP) optimized the bonding quality of Resilon/Epiphany (Resilon Research LLC, Madison, CT) root fillings.

  15. Diary as an Instrument of Philosophic Self-research in Creative Work of J.-P. Sartre

    Directory of Open Access Journals (Sweden)

    Natalya S. Shurinova

    2016-12-01

    Full Text Available The article examines the features of diary genre in the works of J.-P. Sartre on the text material, demonstrating an affinity with diary prose, – the novel «Nausea» and «Diary of a strange war». We proceed from the assumption that the relevance of this form is due to Sartre’s genre traits, productive for the formulation of an existential statement. Among them are: a special stylistic organization of the text, the synchronicity of unfinished diary, as well as the possibility of introducing in the text of the indirect recipient and the similarity of the genre with the epistolary form. Each of these features enables Sartre to actualize their own philosophical principles and ideas: openness of the existential project, intentionality of consciousness and the need to examine the person in the aspect of its perception of the world, the senselessness of introspection and self-knowledge of the other. During the analysis we refer to the works of Russian (E.M. Evnin, S.L. Fokin and French Sartre-experts (J.F. Luetta, M. Comte, J. Degi, J. Simon, as well as theoretical studies of the genre (works of Y.M. Lotman, O. Yegorov, A.A. Zaliznyak, L.N. Letyagin, A. Girard, F. Lejeune.

  16. Wolf-Hirschhorn (4p-) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion.

    Science.gov (United States)

    Chen, Chih-Ping; Su, Yi-Ning; Chen, Yi-Yung; Su, Jun-Wei; Chern, Schu-Rern; Chen, Yu-Ting; Chen, Wen-Lin; Chen, Li-Feng; Wang, Wayseen

    2011-12-01

    To present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) associated with microduplications at 8p and 10p in a fetus with an apparently pure 4p deletion. A 35-year-old gravida 2, para 1 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Her husband was 38 years of age. There was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(4p16.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 6.5-Mb deletion at 4p16.3-p16.1, a 1.2-Mb microduplication at 8p22-p21.3, and a 1.1-Mb microduplication at 10p15.3, or arr cgh 4p16.3p16.1 (0-6,531,998 bp)×1, 8p22p21.3 (18,705,388-19,940,445 bp)×3, 10p15.3 (0-1,105,065 bp)×3. Polymorphic DNA marker analysis confirmed a paternal origin of 4p deletion. Prenatal ultrasound revealed facial dysmorphism and hypospadias. The aCGH analysis of the parents revealed no genomic imbalance. Fluorescence in situ hybridization study showed an unbalanced reciprocal translocation between chromosomes 4 and 10 at bands 4p16.1 and 10p15.3. The cytogenetic result, thus, was 46,XY,der(4)t(4;10)(p16.1;p15.3),dup(8)(p21.3p22). The parents elected to terminate the pregnancy, and a 470-g malformed fetus was delivered. The present case provides evidence that an apparently pure 4p deletion can be associated with subtle chromosome imbalances in other chromosomes. Copyright © 2011. Published by Elsevier B.V.

  17. A Higher-Calorie Refeeding Protocol Does Not Increase Adverse Outcomes in Adult Patients with Eating Disorders.

    Science.gov (United States)

    Matthews, Kylie; Hill, Jan; Jeffrey, Shane; Patterson, Susan; Davis, Amanda; Ward, Warren; Palmer, Michelle; Capra, Sandra

    2018-04-12

    Patients with eating disorders (EDs) are often considered a high-risk population to refeed. Current research advises using "start low, go slow" refeeding methods (∼1,000 kcal/day, advancing ∼500 kcal/day every 3 to 4 days) in adult patients with severe EDs to prevent the development of refeeding syndrome (RFS), typically characterized by decreases in serum electrolyte levels and fluid shifts. To compare the incidence of RFS and related outcomes using a low-calorie protocol (LC) (1,000 kcal) or a higher-calorie protocol (HC) (1,500 kcal) in medically compromised adult patients with EDs. This was a retrospective pre-test-post-test study. One hundred and nineteen participants with EDs, medically admitted to a tertiary hospital in Brisbane, Australia, between December 2010 and January 2017, were included (LC: n=26, HC: n=93). The HC refeeding protocol was implemented in September 2013. Differences in prevalence of electrolyte disturbances, hypoglycemia, edema, and RFS diagnoses were examined. χ 2 tests, Kruskal-Wallis H test, analysis of variance, and independent t tests were used to compare data between the two protocols. Descriptors were similar between groups (LC: 28±9 years, 96% female, 85% with anorexia nervosa, 31% admitted primarily because of clinical symptoms of exacerbated ED vs HC: 27±9 years, 97% female, 84% with anorexia nervosa, 44% admitted primarily because of clinical symptoms of exacerbated ED, P>0.05). Participants refed using the LC protocol had higher incidence rates of hypoglycemia (LC: 31% vs HC: 10%, P=0.012), with no statistical or clinical differences in electrolyte disturbances (LC: 65% vs HC: 45%, P=0.079), edema (LC: 8% vs HC: 6%, P=0.722) or diagnosed RFS (LC: 4% vs HC: 1%, P=0.391). A higher-calorie refeeding protocol appears to be safe, with no differences in rates of electrolyte disturbances or clinically diagnosed RFS and a lower incidence of hypoglycemia. Future research examining higher-calorie intakes, similar to those

  18. Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma.

    Science.gov (United States)

    Herr, D; Bettendorf, H; Denschlag, D; Keck, C; Pietrowski, D

    2006-10-01

    To investigate the association between the occurrence of uterine leiomyoma and two SNPs of the CYP 2A13 and CYP 1A1 genes. Prospective case control study with 132 women with clinically and surgically diagnosed uterine leiomyoma and 260 controls. Genotyping was performed by polymerase chain reaction (PCR) based amplification of CYP 2A13 and CYP 1A1 genes, and restriction fragment length polymorphism (RFLP) analysis. Comparing women with uterine leiomyoma and controls, we demonstrate statistical significant differences of allele frequency and genotype distribution for the CYP 1A1 polymorphism (P = 0.025 and P = 0.046, respectively). Furthermore, for the CYP 2A13 polymorphism we found a significant difference concerning allele frequency (P = 0.033). However, for the genotype distribution, only borderline significance was observed (P = 0.064). The CYP 2A13 and CYP 1A1 SNPs are associated with uterine leiomyoma in a Caucasian population and may contribute to the understanding of the pathogenic mechanisms of uterine leiomyoma.

  19. The P1approximation in the transport of beta rays

    International Nuclear Information System (INIS)

    Legarda, F.; Idoeta, R.; Herranz, M.

    1994-01-01

    A validation test for the p1 approximation to the linear transport of electrons in planar geometry has been performed. The p1 approximation is shown to be a good option for the description of the transport of beta rays with endpoint energies between 400kev and 3.5Mev through aluminium foils . This approximation together with the use of only elastic interactions of electrons with atoms has found good agreement with experimental results . A calculation has been made of the fraction of transmitted electrons through foils, solving the transport equation for planar geometry in the p1 approximation and assuming that only elastic scattering processes take place. The boundary condition at the entrance of the foil was a collimated beta source, while at the end of the foil has been adopted a vaccum boundary condition.Sources considered are those for which experimental and calculated spectrum shapes are known to agree. The calculated fractional transmission through different absorber thicknesses is found to have an exponential shape . Besides this fact the attenuation coefficients found ,when compared with those empirically obtained, agree to within 5%. 1 fig.; 4 refs. (author)

  20. A 1MeV, 1A negative ion accelerator test facility

    International Nuclear Information System (INIS)

    Hanada, M.; Dairaku, M.; Inoue, T.; Miyamoto, K.; Ohara, Y.; Okumura, Y.; Watanabe, K.; Yokoyama, K.

    1995-01-01

    For the Proof-of-Principle test of negative ion acceleration up to 1 MeV, the beam energy required for ITER, a negative ion test facility named MeV Test Facility (MTF) and an ion source/accelerator have been designed and constructed. They are designed to produce a 1 MeV H- beam at a low source pressure of 0.13Pa. The MTF has a power supply system, which constituts of a 1MV, 1A, 60 s Cockcroft-Walton type dc high energy generator and power supplies for negative ion generation and extraction (ion source power supplies). The negative ion source/accelerator is composed of a cesiated volume source and a 5-stage, multi-aperture, electrostatic accelerator. The MTF and the ion source/accelerator have been completed, and the accelertion test up to 1 MeV of the H- ions has started. (orig.)

  1. Disease - MicrobeDB.jp | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...File name: disease.tar.gz File URL: ftp://ftp.biosciencedbc.jp/archive/microbedb/...iption Download License Update History of This Database Site Policy | Contact Us Disease - MicrobeDB.jp | LSDB Archive ...

  2. Laboratory-based testing to evaluate abuse-deterrent formulations and satisfy the Food and Drug Administration's recommendation for Category 1 Testing.

    Science.gov (United States)

    Altomare, Christopher; Kinzler, Eric R; Buchhalter, August R; Cone, Edward J; Costantino, Anthony

    The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. Study protocols are designed to evaluate common abuse patterns of prescription medications as well as more advanced methods that have been reported on drug abuse websites and forums. Because FDA believes Category 1 testing should fully characterize the abuse-deterrent characteristics of an investigational formulation, Category 1 testing is time consuming and requires specialized laboratory resources as well as advanced knowledge of prescription medication abuse. Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of an investigational formulation. In this article, we will provide a general overview of the methods of manipulation and routes of administration commonly utilized by prescription drug abusers, how those methods and routes are evaluated in a laboratory setting, and discuss data intake, analysis, and reporting to satisfy FDA's Category 1 testing requirements.

  3. Authentication Test-Based the RFID Authentication Protocol with Security Analysis

    Directory of Open Access Journals (Sweden)

    Minghui Wang

    2014-08-01

    Full Text Available To the problem of many recently proposed RFID authentication protocol was soon find security holes, we analyzed the main reason, which is that protocol design is not rigorous, and the correctness of the protocol cannot be guaranteed. To this end, authentication test method was adopted in the process of the formal analysis and strict proof to the proposed RFID protocol in this paper. Authentication Test is a new type of analysis and design method of security protocols based on Strand space model, and it can be used for most types of the security protocols. After analysis the security, the proposed protocol can meet the RFID security demand: information confidentiality, data integrity and identity authentication.

  4. Radiative E1-decay of charmonium 1P1 level within sum rules of quantum chromodynamics

    International Nuclear Information System (INIS)

    Martynenko, A.P.

    1991-01-01

    Analysis of radiative decay of 1 P 11 S 0 + γ charmonium within sum rules of quantum chromodynamics was conducted. The sum rule, taking account of gluon exponential correction, was obtained, and width of Χ → η c + γ decay was calculated

  5. Experiment data report for Semiscale Mod-1 Test S-28-1 (steam generator tube rupture test series)

    International Nuclear Information System (INIS)

    Collins, B.L.; Coppin, C.E.; Sackett, K.E.

    1977-10-01

    Recorded test data are presented for Test S-28-1 of the Semiscale Mod-1 steam generator tube rupture test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-28-1 was conducted from initial conditions of 15 767 kPa and 557 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact and broken loops to simulate emergency core coolant injection in a PWR. Sixty steam generator tube ruptures were simulated by a controlled injection from a heated accumulator into the intact loop hot leg

  6. Measurement of the production cross section ratio $\\sigma(\\chi_{b2}(1\\mathrm{P}))/ \\sigma(\\chi_{b1}(1\\mathrm{P}))$ in pp collisions at $\\sqrt{s}$ = 8 TeV

    CERN Document Server

    Khachatryan, Vardan; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Luyckx, Sten; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Van De Klundert, Merijn; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Daci, Nadir; Heracleous, Natalie; Keaveney, James; Lowette, Steven; Maes, Michael; Olbrechts, Annik; Python, Quentin; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Dobur, Didar; Favart, Laurent; Gay, Arnaud; Grebenyuk, Anastasia; Léonard, Alexandre; Mohammadi, Abdollah; Perniè, Luca; Reis, Thomas; Seva, Tomislav; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Costantini, Silvia; Crucy, Shannon; Dildick, Sven; Fagot, Alexis; Garcia, Guillaume; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Salva Diblen, Sinem; Sigamani, Michael; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bruno, Giacomo; Castello, Roberto; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Nuttens, Claude; Pagano, Davide; Perrini, Lucia; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Aldá Júnior, Walter Luiz; Alves, Gilvan; Brito, Lucas; Correa Martins Junior, Marcos; Dos Reis Martins, Thiago; Mora Herrera, Clemencia; Pol, Maria Elena; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Malbouisson, Helena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santaolalla, Javier; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Bernardes, Cesar Augusto; Dogra, Sunil; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Aleksandrov, Aleksandar; Genchev, Vladimir; Iaydjiev, Plamen; Marinov, Andrey; Piperov, Stefan; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Tcholakov, Vanio; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Du, Ran; Jiang, Chun-Hua; Liang, Song; Plestina, Roko; Tao, Junquan; Wang, Xianyou; Wang, Zheng; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Qiang; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Mekterovic, Darko; Sudic, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Bodlak, Martin; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; Ellithi Kamel, Ali; Mahmoud, Mohammed; Radi, Amr; Kadastik, Mario; Murumaa, Marion; Raidal, Martti; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Rander, John; Rosowsky, André; Titov, Maksym; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Charlot, Claude; Dahms, Torsten; Dalchenko, Mykhailo; Dobrzynski, Ludwik; Filipovic, Nicolas; Florent, Alice; Granier de Cassagnac, Raphael; Mastrolorenzo, Luca; Miné, Philippe; Mironov, Camelia; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Paganini, Pascal; Regnard, Simon; Salerno, Roberto; Sauvan, Jean-Baptiste; Sirois, Yves; Veelken, Christian; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Aubin, Alexandre; Bloch, Daniel; Brom, Jean-Marie; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Beaupere, Nicolas; Boudoul, Gaelle; Bouvier, Elvire; Brochet, Sébastien; Carrillo Montoya, Camilo Andres; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Kurca, Tibor; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Ruiz Alvarez, José David; Sabes, David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Xiao, Hong; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Bontenackels, Michael; Edelhoff, Matthias; Feld, Lutz; Hindrichs, Otto; Klein, Katja; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Dietz-Laursonn, Erik; Duchardt, Deborah; Erdmann, Martin; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Millet, Philipp; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Weber, Martin; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Haj Ahmad, Wael; Heister, Arno; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Lingemann, Joschka; Nowack, Andreas; Nugent, Ian Michael; Perchalla, Lars; Pooth, Oliver; Stahl, Achim; Asin, Ivan; Bartosik, Nazar; Behr, Joerg; Behrenhoff, Wolf; Behrens, Ulf; Bell, Alan James; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Burgmeier, Armin; Cakir, Altan; Calligaris, Luigi; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Garay Garcia, Jasone; Geiser, Achim; Gunnellini, Paolo; Hauk, Johannes; Hempel, Maria; Horton, Dean; Jung, Hannes; Kalogeropoulos, Alexis; Kasemann, Matthias; Katsas, Panagiotis; Kieseler, Jan; Kleinwort, Claus; Krücker, Dirk; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lobanov, Artur; Lohmann, Wolfgang; Lutz, Benjamin; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mittag, Gregor; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Nayak, Aruna; Novgorodova, Olga; Nowak, Friederike; Ntomari, Eleni; Perrey, Hanno; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Ribeiro Cipriano, Pedro M; Ron, Elias; Sahin, Mehmet Özgür; Salfeld-Nebgen, Jakob; Saxena, Pooja; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Schröder, Matthias; Seitz, Claudia; Spannagel, Simon; Vargas Trevino, Andrea Del Rocio; Walsh, Roberval; Wissing, Christoph; Aldaya Martin, Maria; Blobel, Volker; Centis Vignali, Matteo; Draeger, Arne-Rasmus; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Görner, Martin; Haller, Johannes; Hoffmann, Malte; Höing, Rebekka Sophie; Kirschenmann, Henning; Klanner, Robert; Kogler, Roman; Lange, Jörn; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Ott, Jochen; Peiffer, Thomas; Pietsch, Niklas; Poehlsen, Jennifer; Pöhlsen, Thomas; Rathjens, Denis; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Seidel, Markus; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Feindt, Michael; Frensch, Felix; Giffels, Manuel; Hartmann, Frank; Hauth, Thomas; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Kuznetsova, Ekaterina; Lobelle Pardo, Patricia; Mozer, Matthias Ulrich; Müller, Thomas; Nürnberg, Andreas; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Röcker, Steffen; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weiler, Thomas; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Markou, Athanasios; Markou, Christos; Psallidas, Andreas; Topsis-Giotis, Iasonas; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Stiliaris, Efstathios; Aslanoglou, Xenofon; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Bencze, Gyorgy; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Swain, Sanjay Kumar; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Bhawandeep, Bhawandeep; Kalsi, Amandeep Kaur; Kaur, Manjit; Mittal, Monika; Nishu, Nishu; Singh, Jasbir; Kumar, Ashok; Kumar, Arun; Ahuja, Sudha; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Varun; Banerjee, Sunanda; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dutta, Suchandra; Gomber, Bhawna; Jain, Sandhya; Jain, Shilpi; Khurana, Raman; Modak, Atanu; Mukherjee, Swagata; Roy, Debarati; Sarkar, Subir; Sharan, Manoj; Abdulsalam, Abdulla; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Banerjee, Sudeshna; Bhowmik, Sandeep; Chatterjee, Rajdeep Mohan; Dewanjee, Ram Krishna; Dugad, Shashikant; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Parida, Bibhuti; Sudhakar, Katta; Wickramage, Nadeesha; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Goldouzian, Reza; Jafari, Abideh; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Chhibra, Simranjit Singh; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Selvaggi, Giovanna; Silvestris, Lucia; Singh, Gurpreet; Venditti, Rosamaria; Verwilligen, Piet; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gallo, Elisabetta; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Ferro, Fabrizio; Lo Vetere, Maurizio; Robutti, Enrico; Tosi, Silvano; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Lucchini, Marco Toliman; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Martelli, Arabella; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bisello, Dario; Branca, Antonio; Carlin, Roberto; Checchia, Paolo; Dall'Osso, Martino; Dorigo, Tommaso; Dosselli, Umberto; Galanti, Mario; Gasparini, Fabrizio; Gasparini, Ugo; Giubilato, Piero; Gonella, Franco; Gozzelino, Andrea; Kanishchev, Konstantin; Lacaprara, Stefano; Margoni, Martino; Montecassiano, Fabio; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Tosi, Mia; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Gabusi, Michele; Ratti, Sergio P; Riccardi, Cristina; Salvini, Paola; Vitulo, Paolo; Biasini, Maurizio; Bilei, Gian Mario; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Romeo, Francesco; Saha, Anirban; Santocchia, Attilio; Spiezia, Aniello; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Moon, Chang-Seong; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Squillacioti, Paola; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Vernieri, Caterina; Barone, Luciano; Cavallari, Francesca; D'imperio, Giulia; Del Re, Daniele; Diemoz, Marcella; Grassi, Marco; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Micheli, Francesco; Nourbakhsh, Shervin; Organtini, Giovanni; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Soffi, Livia; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Casasso, Stefano; Costa, Marco; Degano, Alessandro; Demaria, Natale; Dujany, Giulio; Finco, Linda; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Ortona, Giacomo; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Montanino, Damiana; Schizzi, Andrea; Umer, Tomo; Zanetti, Anna; Chang, Sunghyun; Kropivnitskaya, Anna; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Park, Hyangkyu; Sakharov, Alexandre; Son, Dong-Chul; Kim, Tae Jeong; Kim, Jae Yool; Song, Sanghyeon; Choi, Suyong; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Byounghoon; Lee, Kyong Sei; Park, Sung Keun; Roh, Youn; Choi, Minkyoo; Kim, Ji Hyun; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Ryu, Min Sang; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kim, Donghyun; Kwon, Eunhyang; Lee, Jongseok; Seo, Hyunkwan; Yu, Intae; Juodagalvis, Andrius; Komaragiri, Jyothsna Rani; Md Ali, Mohd Adli Bin; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Reucroft, Steve; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Khalid, Shoaib; Khan, Wajid Ali; Khurshid, Taimoor; Shah, Mehar Ali; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michał; Wolszczak, Weronika; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Varela, Joao; Vischia, Pietro; Golutvin, Igor; Gorbunov, Ilya; Karjavin, Vladimir; Konoplyanikov, Viktor; Korenkov, Vladimir; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Mitsyn, Valeri Valentinovitch; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Skatchkov, Nikolai; Smirnov, Vitaly; Tikhonenko, Elena; Yuldashev, Bekhzod S; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Spiridonov, Alexander; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Vinogradov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Snigirev, Alexander; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Ekmedzic, Marko; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Battilana, Carlo; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Merino, Gonzalo; Navarro De Martino, Eduardo; Pérez Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Brun, Hugues; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Lloret Iglesias, Lara; Brochero Cifuentes, Javier Andres; Cabrillo, Iban Jose; Calderon, Alicia; Duarte Campderros, Jordi; Fernandez, Marcos; Gomez, Gervasio; Graziano, Alberto; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Benaglia, Andrea; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Bernet, Colin; Bianchi, Giovanni; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Bondu, Olivier; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Cerminara, Gianluca; Colafranceschi, Stefano; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; David Tinoco Mendes, Andre; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Dobson, Marc; Dordevic, Milos; Dupont-Sagorin, Niels; Elliott-Peisert, Anna; Eugster, Jürg; Franzoni, Giovanni; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Girone, Maria; Glege, Frank; Guida, Roberto; Gundacker, Stefan; Guthoff, Moritz; Hammer, Josef; Hansen, Magnus; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Marrouche, Jad; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Morovic, Srecko; Mulders, Martijn; Musella, Pasquale; Orsini, Luciano; Pape, Luc; Perez, Emmanuelle; Perrozzi, Luca; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Pimiä, Martti; Piparo, Danilo; Plagge, Michael; Racz, Attila; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Sharma, Archana; Siegrist, Patrice; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Spiga, Daniele; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Treille, Daniel; Tsirou, Andromachi; Veres, Gabor Istvan; Vlimant, Jean-Roch; Wardle, Nicholas; Wöhri, Hermine Katharina; Wollny, Heiner; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Bortignon, Pierluigi; Buchmann, Marco-Andrea; Casal, Bruno; Chanon, Nicolas; Deisher, Amanda; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Dünser, Marc; Eller, Philipp; Grab, Christoph; Hits, Dmitry; Lustermann, Werner; Mangano, Boris; Marini, Andrea Carlo; Martinez Ruiz del Arbol, Pablo; Meister, Daniel; Mohr, Niklas; Nägeli, Christoph; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pauss, Felicitas; Peruzzi, Marco; Quittnat, Milena; Rebane, Liis; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Theofilatos, Konstantinos; Wallny, Rainer; Weber, Hannsjoerg Artur; Amsler, Claude; Canelli, Maria Florencia; Chiochia, Vincenzo; De Cosa, Annapaola; Hinzmann, Andreas; Hreus, Tomas; Kilminster, Benjamin; Lange, Clemens; Millan Mejias, Barbara; Ngadiuba, Jennifer; Robmann, Peter; Ronga, Frederic Jean; Taroni, Silvia; Verzetti, Mauro; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Ferro, Cristina; Kuo, Chia-Ming; Lin, Willis; Lu, Yun-Ju; Volpe, Roberta; Yu, Shin-Shan; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Grundler, Ulysses; Hou, George Wei-Shu; Kao, Kai-Yi; Lei, Yeong-Jyi; Liu, Yueh-Feng; Lu, Rong-Shyang; Majumder, Devdatta; Petrakou, Eleni; Tzeng, Yeng-Ming; Wilken, Rachel; Asavapibhop, Burin; Srimanobhas, Norraphat; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Akin, Ilina Vasileva; Bilin, Bugra; Bilmis, Selcuk; Gamsizkan, Halil; Karapinar, Guler; Ocalan, Kadir; Sekmen, Sezen; Surat, Ugur Emrah; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Bahtiyar, Hüseyin; Barlas, Esra; Cankocak, Kerem; Vardarli, Fuat Ilkehan; Yücel, Mete; Levchuk, Leonid; Sorokin, Pavel; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Frazier, Robert; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Senkin, Sergey; Smith, Vincent J; Williams, Thomas; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Burton, Darren; Colling, David; Cripps, Nicholas; Cutajar, Michael; Dauncey, Paul; Davies, Gavin; Della Negra, Michel; Dunne, Patrick; Ferguson, William; Fulcher, Jonathan; Futyan, David; Gilbert, Andrew; Hall, Geoffrey; Iles, Gregory; Jarvis, Martyn; Karapostoli, Georgia; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Mathias, Bryn; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Raymond, David Mark; Rogerson, Samuel; Rose, Andrew; Seez, Christopher; Sharp, Peter; Tapper, Alexander; Vazquez Acosta, Monica; Virdee, Tejinder; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Martin, William; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Dittmann, Jay; Hatakeyama, Kenichi; Kasmi, Azeddine; Liu, Hongxuan; Scarborough, Tara; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Lawson, Philip; Richardson, Clint; Rohlf, James; Sperka, David; St John, Jason; Sulak, Lawrence; Alimena, Juliette; Berry, Edmund; Bhattacharya, Saptaparna; Christopher, Grant; Cutts, David; Demiragli, Zeynep; Ferapontov, Alexey; Garabedian, Alex; Heintz, Ulrich; Kukartsev, Gennadiy; Laird, Edward; Landsberg, Greg; Luk, Michael; Narain, Meenakshi; Segala, Michael; Sinthuprasith, Tutanon; Speer, Thomas; Swanson, Joshua; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Lander, Richard; Miceli, Tia; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Searle, Matthew; Shalhout, Shalhout; Smith, John; Squires, Michael; Stolp, Dustin; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Cousins, Robert; Everaerts, Pieter; Farrell, Chris; Hauser, Jay; Ignatenko, Mikhail; Rakness, Gregory; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Babb, John; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Ivova Rikova, Mirena; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Liu, Hongliang; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Nguyen, Harold; Olmedo Negrete, Manuel; Shrinivas, Amithabh; Sumowidagdo, Suharyo; Wimpenny, Stephen; Andrews, Warren; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Evans, David; Holzner, André; Kelley, Ryan; Klein, Daniel; Lebourgeois, Matthew; Letts, James; Macneill, Ian; Olivito, Dominick; Padhi, Sanjay; Palmer, Christopher; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Sudano, Elizabeth; Tadel, Matevz; Tu, Yanjun; Vartak, Adish; Welke, Charles; Würthwein, Frank; Yagil, Avraham; Yoo, Jaehyeok; Barge, Derek; Bradmiller-Feld, John; Campagnari, Claudio; Danielson, Thomas; Dishaw, Adam; Flowers, Kristen; Franco Sevilla, Manuel; Geffert, Paul; George, Christopher; Golf, Frank; Gouskos, Loukas; Incandela, Joe; Justus, Christopher; Mccoll, Nickolas; Richman, Jeffrey; Stuart, David; To, Wing; West, Christopher; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Di Marco, Emanuele; Duarte, Javier; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Rogan, Christopher; Spiropulu, Maria; Timciuc, Vladlen; Wilkinson, Richard; Xie, Si; Zhu, Ren-Yuan; Azzolini, Virginia; Calamba, Aristotle; Carlson, Benjamin; Ferguson, Thomas; Iiyama, Yutaro; Paulini, Manfred; Russ, James; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Ford, William T; Gaz, Alessandro; Luiggi Lopez, Eduardo; Nauenberg, Uriel; Smith, James; Stenson, Kevin; Ulmer, Keith; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Chu, Jennifer; Dittmer, Susan; Eggert, Nicholas; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Ryd, Anders; Salvati, Emmanuele; Skinnari, Louise; Sun, Werner; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Winstrom, Lucas; Wittich, Peter; Winn, Dave; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Burkett, Kevin; Butler, Joel Nathan; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gao, Yanyan; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hanlon, Jim; Hare, Daryl; Harris, Robert M; Hirschauer, James; Hooberman, Benjamin; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Kaadze, Ketino; Klima, Boaz; Kreis, Benjamin; Kwan, Simon; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Tiehui; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Mishra, Kalanand; Mrenna, Stephen; Musienko, Yuri; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Prokofyev, Oleg; Sexton-Kennedy, Elizabeth; Sharma, Seema; Soha, Aron; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vidal, Richard; Whitbeck, Andrew; Whitmore, Juliana; Yang, Fan; Acosta, Darin; Avery, Paul; Bourilkov, Dimitri; Carver, Matthew; Cheng, Tongguang; Curry, David; Das, Souvik; De Gruttola, Michele; Di Giovanni, Gian Piero; Field, Richard D; Fisher, Matthew; Furic, Ivan-Kresimir; Hugon, Justin; Konigsberg, Jacobo; Korytov, Andrey; Kypreos, Theodore; Low, Jia Fu; Matchev, Konstantin; Milenovic, Predrag; Mitselmakher, Guenakh; Muniz, Lana; Rinkevicius, Aurelijus; Shchutska, Lesya; Snowball, Matthew; Yelton, John; Zakaria, Mohammed; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Prosper, Harrison; Veeraraghavan, Venkatesh; Weinberg, Marc; Baarmand, Marc M; Hohlmann, Marcus; Kalakhety, Himali; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Bazterra, Victor Eduardo; Berry, Douglas; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Khalatyan, Samvel; Kurt, Pelin; Moon, Dong Ho; O'Brien, Christine; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Duru, Firdevs; Haytmyradov, Maksat; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Rahmat, Rahmat; Sen, Sercan; Tan, Ping; Tiras, Emrah; Wetzel, James; Yetkin, Taylan; Yi, Kai; Barnett, Bruce Arnold; Blumenfeld, Barry; Bolognesi, Sara; Fehling, David; Gritsan, Andrei; Maksimovic, Petar; Martin, Christopher; Swartz, Morris; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Bruner, Christopher; Gray, Julia; Kenny III, Raymond Patrick; Malek, Magdalena; Murray, Michael; Noonan, Daniel; Sanders, Stephen; Sekaric, Jadranka; Stringer, Robert; Wang, Quan; Wood, Jeffrey Scott; Barfuss, Anne-Fleur; Chakaberia, Irakli; Ivanov, Andrew; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Saini, Lovedeep Kaur; Shrestha, Shruti; Skhirtladze, Nikoloz; Svintradze, Irakli; Gronberg, Jeffrey; Lange, David; Rebassoo, Finn; Wright, Douglas; Baden, Drew; Belloni, Alberto; Calvert, Brian; Eno, Sarah Catherine; Gomez, Jaime; Hadley, Nicholas John; Kellogg, Richard G; Kolberg, Ted; Lu, Ying; Marionneau, Matthieu; Mignerey, Alice; Pedro, Kevin; Skuja, Andris; Tonjes, Marguerite; Tonwar, Suresh C; Apyan, Aram; Barbieri, Richard; Bauer, Gerry; Busza, Wit; Cali, Ivan Amos; Chan, Matthew; Di Matteo, Leonardo; Dutta, Valentina; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Klute, Markus; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Ma, Teng; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Stephans, George; Stöckli, Fabian; Sumorok, Konstanty; Velicanu, Dragos; Veverka, Jan; Wyslouch, Bolek; Yang, Mingming; Zanetti, Marco; Zhukova, Victoria; Dahmes, Bryan; Gude, Alexander; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Mans, Jeremy; Pastika, Nathaniel; Rusack, Roger; Singovsky, Alexander; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Gonzalez Suarez, Rebeca; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Lazo-Flores, Jose; Malik, Sudhir; Meier, Frank; Snow, Gregory R; Dolen, James; Godshalk, Andrew; Iashvili, Ia; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Haley, Joseph; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Trocino, Daniele; Wang, Ren-Jie; Wood, Darien; Zhang, Jinzhong; Hahn, Kristan Allan; Kubik, Andrew; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Velasco, Mayda; Won, Steven; Brinkerhoff, Andrew; Chan, Kwok Ming; Drozdetskiy, Alexey; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Luo, Wuming; Lynch, Sean; Marinelli, Nancy; Pearson, Tessa; Planer, Michael; Ruchti, Randy; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Brinson, Jessica; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hill, Christopher; Hughes, Richard; Kotov, Khristian; Ling, Ta-Yung; Puigh, Darren; Rodenburg, Marissa; Smith, Geoffrey; Winer, Brian L; Wolfe, Homer; Wulsin, Howard Wells; Driga, Olga; Elmer, Peter; Hebda, Philip; Hunt, Adam; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Piroué, Pierre; Quan, Xiaohang; Saka, Halil; Stickland, David; Tully, Christopher; Werner, Jeremy Scott; Zenz, Seth Conrad; Zuranski, Andrzej; Brownson, Eric; Mendez, Hector; Ramirez Vargas, Juan Eduardo; Barnes, Virgil E; Benedetti, Daniele; Bolla, Gino; Bortoletto, Daniela; De Mattia, Marco; Hu, Zhen; Jha, Manoj; Jones, Matthew; Jung, Kurt; Kress, Matthew; Leonardo, Nuno; Lopes Pegna, David; Maroussov, Vassili; Merkel, Petra; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shi, Xin; Shipsey, Ian; Silvers, David; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Yoo, Hwi Dong; Zablocki, Jakub; Zheng, Yu; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Ecklund, Karl Matthew; Geurts, Frank JM; Li, Wei; Michlin, Benjamin; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Zabel, James; Betchart, Burton; Bodek, Arie; Covarelli, Roberto; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Garcia-Bellido, Aran; Goldenzweig, Pablo; Han, Jiyeon; Harel, Amnon; Khukhunaishvili, Aleko; Petrillo, Gianluca; Vishnevskiy, Dmitry; Ciesielski, Robert; Demortier, Luc; Goulianos, Konstantin; Lungu, Gheorghe; Mesropian, Christina; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Kaplan, Steven; Lath, Amitabh; Panwalkar, Shruti; Park, Michael; Patel, Rishi; Salur, Sevil; Schnetzer, Steve; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Rose, Keith; Spanier, Stefan; York, Andrew; Bouhali, Othmane; Castaneda Hernandez, Alfredo; Eusebi, Ricardo; Flanagan, Will; Gilmore, Jason; Kamon, Teruki; Khotilovich, Vadim; Krutelyov, Vyacheslav; Montalvo, Roy; Osipenkov, Ilya; Pakhotin, Yuriy; Perloff, Alexx; Roe, Jeffrey; Rose, Anthony; Safonov, Alexei; Sakuma, Tai; Suarez, Indara; Tatarinov, Aysen; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Kovitanggoon, Kittikul; Kunori, Shuichi; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Sharma, Monika; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Boutle, Sarah; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Lin, Chuanzhe; Neu, Christopher; Wood, John; Clarke, Christopher; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Sturdy, Jared; Belknap, Donald; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Friis, Evan; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Lanaro, Armando; Lazaridis, Christos; Levine, Aaron; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ross, Ian; Sarangi, Tapas; Savin, Alexander; Smith, Wesley H; Vuosalo, Carl; Woods, Nathaniel

    2015-04-09

    A measurement of the production cross section ratio $\\sigma(\\chi_{b2}(1\\mathrm{P}))/ \\sigma(\\chi_{b1}(1\\mathrm{P}))$ is presented. The $\\chi_{b1}(1\\mathrm{P})$ and $\\chi_{b2}(1\\mathrm{P})$ bottomonium states, promptly produced in pp collisions at $\\sqrt{s}$= 8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays $\\chi_{b1,2}(1\\mathrm{P}) \\rightarrow \\Upsilon(1\\mathrm{S}) + \\gamma$. The emitted photons are measured through their conversion to e$^+$e$^-$ pairs, whose reconstruction allows the two states to be resolved. The $\\Upsilon(1\\mathrm{S})$ is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb$^{-1}$ is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |$\\eta^\\gamma$| < 1.0; the $\\Upsilon(1\\mathrm{S})$ rapidity, |$y^\\Upsilon$| < 1.5; and the $\\Upsilon(1\\mathrm{S})$ transverse momentum, 7 < $p_{\\mathrm{T}}^\\Upsilon$ < 40 GeV. The cross section ratio sh...

  7. Functional characterization of the origin of replication of pRN1 from Sulfolobus islandicus REN1H1.

    Directory of Open Access Journals (Sweden)

    Chijioke J Joshua

    Full Text Available Plasmid pRN1 from Sulfolobus islandicus REN1H1 is believed to replicate by a rolling circle mechanism but its origin and mechanism of replication are not well understood. We sought to create minimal expression vectors based on pRN1 that would be useful for heterologous gene expression in S. acidocaldarius, and in the process improve our understanding of the mechanism of replication. We constructed and transformed shuttle vectors that harbored different contiguous stretches of DNA from pRN1 into S. acidocaldarius E4-39, a uracil auxotroph. A 232-bp region 3' of orf904 was found to be critical for pRN1 replication and is therefore proposed to be the putative origin of replication. This 232-bp region contains a 100-bp stem-loop structure believed to be the double-strand origin of replication. The loop of the 100-bp structure contains a GTG tri-nucleotide motif, a feature that was previously reported to be important for the primase activity of Orf904. This putative origin and the associated orf56 and orf904 were identified as the minimal replicon of pRN1 because transformants of plasmids lacking any of these three features were not recovered. Plasmids lacking orf904 and orf56 but harboring the putative origin were transformable when orf904 and orf56 were provided in-trans; a 75-bp region 5' of the orf904 start codon was found to be essential for this complementation. Detailed knowledge of the pRN1 origin of replication will broaden the application of the plasmid as a genetic tool for Sulfolobus species.

  8. Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

    Science.gov (United States)

    Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

    2017-05-01

    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Assessment of Canine Autologous Conditioned PlasmaTM Cellular and Transforming Growth Factor-β1 Content

    Directory of Open Access Journals (Sweden)

    Samuel P. Franklin

    2018-06-01

    Full Text Available To evaluate (1 the cellular composition of canine ACP™ including using two different preparation protocols with variations on centrifugation time, (2 the effect of different activation protocols on the transforming growth factor (TGF-β1 content in the ACP, and (3 patient factors that might influence platelet concentration of the ACP.ACP was made with blood from 15 dogs using a manufacturer-recommended protocol[1]. Each ACP sample was divided into three aliquots that were activated with calcium chloride (CaCl2, human γ-thrombin (HGT, or not activated. TGF-β1 was quantified in each aliquot using an ELISA and comparisons among activation protocols were performed using a Skillings-Mack test. Correlations between platelet and TGF-β1 concentration were assessed with a Pearson correlation coefficient. ACP was subsequently prepared from an additional 17 dogs using a slightly modified centrifugation protocol and cellular composition was assessed. Effects of dog age, body weight, and hematocrit were assessed for their potential impact on ACP platelet concentration using a multiple linear regression analysis.The mean increase in platelet concentration in the ACP above that in the whole blood was 1.2× (±std 0.62 and leukocyte concentration was a mean of 26% (0.37 that in the whole blood using the standard protocol. There was a significant (p < 0.01 effect of activation on TGF-β1 concentrations with mean concentrations of 4,538 (2,317, 14,948 (13,784, and 14,096 (15,210 pg/ml in aliquots that were not activated or were activated with thrombin or CaCl2 respectively. There were significant correlations between the platelet concentration and TGF-β1 concentration in aliquots that were activated with either thrombin (r = 0.66; p < 0.01 or CaCl2 (r = 0.86, p < 0.0001. The mean increase in platelet concentration was 1.4× (0.62 and the leukocyte concentration was 0.28× (0.13 that in whole blood using the modified ACP preparation protocol. Dog age

  10. Ortholog - MicrobeDB.jp | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us MicrobeDB.jp Ortholog Data detail Data name Ortholog DOI 10.18908/lsdba.nbdc01181-010.V002 V...814 triples - About This Database Database Description Download License Update History of This Database Site Policy | Contact Us Ortholog - MicrobeDB.jp | LSDB Archive ...

  11. Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.

    Science.gov (United States)

    Josipovic, Ivana; Pflüger, Beatrice; Fork, Christian; Vasconez, Andrea E; Oo, James A; Hitzel, Juliane; Seredinski, Sandra; Gamen, Elisabetta; Heringdorf, Dagmar Meyer Zu; Chen, Wei; Looso, Mario; Pullamsetti, Soni Savai; Brandes, Ralf P; Leisegang, Matthias S

    2018-03-01

    Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells. In vitro transcription and translation as well as coding potential assessment showed that LISPR1 is indeed noncoding. LISPR1 was localized in both cytoplasm and nucleus and harbored a PolyA tail at the 3'end. In human umbilical vein endothelial cells, as well as human lung tissue, qRT-PCR and RNA-Seq revealed high expression of LISPR1. S1PR1 and LISPR1 were downregulated in human pulmonary diseases such as COPD. LISPR1 but also S1PR1 were induced by inflammation, shear stress and statins. Knockdown of LISPR1 attenuated endothelial S1P-induced migration and spheroid outgrowth of endothelial cells. LISPR1 knockdown decreased S1PR1 expression, which was paralleled by an increase of the binding of the transcriptional repressor ZNF354C to the S1PR1 promoter and a reduction of the recruitment of RNA Polymerase II to the S1PR1 5'end. This resulted in attenuated S1PR1 expression and attenuated S1P downstream signaling. Collectively, the disease relevant lncRNA LISPR1 acts as a novel regulatory unit important for S1PR1 expression and endothelial cell function. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Oxidized LDL-induced angiogenesis involves sphingosine 1-phosphate: prevention by anti-S1P antibody.

    Science.gov (United States)

    Camaré, Caroline; Trayssac, Magali; Garmy-Susini, Barbara; Mucher, Elodie; Sabbadini, Roger; Salvayre, Robert; Negre-Salvayre, Anne

    2015-01-01

    Neovascularization occurring in atherosclerotic lesions may promote plaque expansion, intraplaque haemorrhage and rupture. Oxidized LDL (oxLDL) are atherogenic, but their angiogenic effect is controversial; both angiogenic and anti-angiogenic effects have been reported. The angiogenic mechanism of oxLDL is partly understood, but the role of the angiogenic sphingolipid, sphingosine 1-phosphate (S1P), in this process is not known. Thus, we investigated whether S1P is involved in the oxLDL-induced angiogenesis and whether an anti-S1P monoclonal antibody can prevent this effect. Angiogenesis was assessed by capillary tube formation by human microvascular endothelial cells (HMEC-1) cultured on Matrigel and in vivo by the Matrigel plug assay in C57BL/6 mice. Human oxLDL exhibited a biphasic angiogenic effect on HMEC-1; low concentrations were angiogenic, higher concentrations were cytotoxic. The angiogenic response to oxLDL was blocked by the sphingosine kinase (SPHK) inhibitor, dimethylsphingosine, by SPHK1-siRNA and by an anti-S1P monoclonal antibody. Moreover, inhibition of oxLDL uptake and subsequent redox signalling by anti-CD36 and anti-LOX-1 receptor antibodies and by N-acetylcysteine, respectively, blocked SPHK1 activation and tube formation. In vivo, in the Matrigel plug assay, low concentrations of human oxLDL or murine oxVLDL also triggered angiogenesis, which was prevented by i.p. injection of the anti-S1P antibody. These data highlight the role of S1P in angiogenesis induced by oxLDL both in HMEC-1 cultured on Matrigel and in vivo in the Matrigel plug model in mice, and demonstrate that the anti-S1P antibody effectively blocks the angiogenic effect of oxLDL. © 2014 The British Pharmacological Society.

  13. p27{sup Kip1} inhibits tissue factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Breitenstein, Alexander, E-mail: alexander.breitenstein@usz.ch [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland); Akhmedov, Alexander; Camici, Giovanni G.; Lüscher, Thomas F.; Tanner, Felix C. [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland)

    2013-10-04

    Highlights: •p27{sup Kip1}regulates the expression of tissue factor at the transcriptional level. •This inhibitory effect of p27{sup Kip1} is independently of its cell regulatory action. •The current study provides new insights into a pleiotrophic function of p27{sup Kip1}. -- Abstract: Background: The cyclin-dependent kinase inhibitor (CDKI) p27{sup Kip1} regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27{sup Kip1} influences the expression of TF. Methods and results: p27{sup Kip1} overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24 h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n = 4; P < 0.001) in cells transfected with p27{sup Kip1}. In line with this, p27{sup Kip1} overexpression reduced cytokine-induced TF mRNA expression (n = 4; P < 0.01) and TF promotor activity (n = 4; P < 0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27{sup Kip1} overexpression. Conclusion: This in vitro study suggests that p27{sup Kip1} inhibits TF expression at the transcriptional level. These data indicate an interaction between p27{sup Kip1} and TF in important pathological alterations such as atherosclerosis and vascular remodeling.

  14. Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts After Filtration Surgery for Glaucoma.

    Science.gov (United States)

    Aoyama-Araki, Yuka; Honjo, Megumi; Uchida, Takatoshi; Yamagishi, Reiko; Kano, Kuniyuki; Aoki, Junken; Aihara, Makoto

    2017-04-01

    To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid samples taken before and after filtration surgery and S1P-induced human conjunctival fibroblast (HCF) responses. Levels of S1P and its related sphingophospholipids in aqueous fluid obtained immediately before and after filtration surgery were determined by liquid chromatography-tandem mass spectrometry. HCFs were used for all in vitro experiments. The expression of five S1P receptor subtypes in HCFs was examined by quantitative real-time PCR. The effect of S1P and receptor-specific antagonists on HCF viability and cell migration was assessed by WST-1 assay and scratch migration assay, respectively. Differentiation to myofibroblasts and extracellular matrix production was evaluated by examining changes in F-actin, α-smooth muscle actin (αSMA), and collagen expression with immunocytochemistry, Western blotting, and collagen accumulation assay, respectively. No significant S1P levels in the aqueous fluid samples were detectable immediately before surgery, but postoperative levels of several lysophospholipids, including S1P, dehydro-S1P, and sphingosine, were significantly increased to bioactive concentrations in aqueous fluid in the blebs (P S1P receptor subtypes was detected in HCFs. Although S1P levels did not influence HCF proliferation, S1P enhanced cell migration, which could be inhibited by the S1P2 antagonist JTE 013. F-actin, αSMA, and collagen expression was significantly increased by S1P stimulation and was reduced by JTE 013. Bioactive S1P concentrations were present in the aqueous fluid at the end of filtration surgery. S1P activated HCFs via S1P2 receptors. These results revealed the potential of S1P2 antagonists in preventing scarring after glaucoma filtration surgery.

  15. The 1st VIPEX Software Testing Report (Version 3.1)

    International Nuclear Information System (INIS)

    Choi, Sun Yeong; Jung, Woo Sik; Seo, Jae Seung

    2009-09-01

    The purposes of this report are (1) to perform a Verification and Validation (V and V) test for the VIPEX(Vital-area Identification Package EXpert) software and (2) to improve a software quality through the V and V test. The VIPEX was developed in Korea Atomic Energy Research Institute (KAERI) for the Vital Area Identification (VAI) of nuclear power plants. The version of the VIPEX which was distributed is 3.1. The VIPEX was revised based on the first V and V test and the second V and V test will be performed. We have performed the following tasks for the first V and V test on Windows XP and VISTA operating systems: - Testing basic function including fault tree editing - Writing formal reports

  16. Topic 1. Steels for light water reactor pressure vessels

    International Nuclear Information System (INIS)

    Brumovsky, M.; Brynda, J.; Kepka, M.; Barackova, L.; Vacek, M.; Havel, S.; Cukr, B.; Protiva, K.; Petrman, I.; Tvrdy, M.; Hyspecka, L.; Mazanec, K.; Kupca, L.; Brezina, M.

    1980-01-01

    Part 1 of the Proceedings consists of papers on the criteria for the selection and comparison of the properties of steel for pressure vessels and on the metallurgy of the said steels, the selection of suitable material for internal tubing systems, the manufacture of high-alloy steels for WWER components, the mechanical and metallurgical properties of steel 22K for WWER 440 pressure components, and of steel 10MnNi2Mo for the WWER primary coolant circuit, and the metallographic assessment of steel 0Kh18N10T. (J.P.)

  17. ORR irradiation experiment OF-1: accelerated testing of HTGR fuel

    International Nuclear Information System (INIS)

    Tiegs, T.N.; Long, E.L. Jr.; Kania, M.J.; Thoms, K.R.; Allen, E.J.

    1977-08-01

    The OF-1 capsule, the first in a series of High-Temperature Gas-Cooled Reactor fuel irradiations in the Oak Ridge Research Reactor, was irradiated for more than 9300 hr at full reactor power (30 MW). Peak fluences of 1.08 x 10 22 neutrons/cm 2 (> 0.18 MeV) were achieved. General Atomic Company's magazine P13Q occupied the upper two-thirds of the test space and the ORNL magazine OF-1 the lower one-third. The ORNL portion tested various HTGR recycle particles and fuel bonding matrices at accelerated flux levels under reference HTGR irradiation conditions of temperature, temperature gradient, and fast fluence exposure

  18. Nuclear effects in protonium formation low-energy three-body reaction: p̄ + (pμ1s → (p̄pα + μ−: Strong p̄–p interaction in p̄ + (pμ1s

    Directory of Open Access Journals (Sweden)

    Sultanov Renat A.

    2016-01-01

    Full Text Available A three-charge-particle system (p̄, μ−, p+ with an additional matter-antimatter, i.e. p̄–p+, nuclear interaction is the subject of this work. Specifically, we carry out a few-body computation of the following protonium formation reaction: p̄ + (p+μ−1s → (p̄p+1s + μ−, where p+ is a proton, p̄ is an antiproton, μ− is a muon, and a bound state of p+ and its counterpart p̄ is a protonium atom: Pn = (p̄p+. The low-energy cross sections and rates of the Pn formation reaction are computed in the framework of a Faddeev-like equation formalism. The strong p̄–p+ interaction is approximately included in this calculation.

  19. Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3.

    Science.gov (United States)

    Shi, Z; Li, Z; Li, Z J; Cheng, K; Du, Y; Fu, H; Khuri, F R

    2015-05-07

    The cyclin-dependent kinase (CDK) inhibitor 1A, p21/Cip1, is a vital cell cycle regulator, dysregulation of which has been associated with a large number of human malignancies. One critical mechanism that controls p21 function is through its degradation, which allows the activation of its associated cell cycle-promoting kinases, CDK2 and CDK4. Thus delineating how p21 is stabilized and degraded will enhance our understanding of cell growth control and offer a basis for potential therapeutic interventions. Here we report a novel regulatory mechanism that controls the dynamic status of p21 through its interaction with Cdk5 and Abl enzyme substrate 1 (Cables1). Cables1 has a proposed role as a tumor suppressor. We found that upregulation of Cables1 protein was correlated with increased half-life of p21 protein, which was attributed to Cables1/p21 complex formation and supported by their co-localization in the nucleus. Mechanistically, Cables1 interferes with the proteasome (Prosome, Macropain) subunit alpha type 3 (PSMA3) binding to p21 and protects p21 from PSMA3-mediated proteasomal degradation. Moreover, silencing of p21 partially reverses the ability of Cables1 to induce cell death and inhibit cell proliferation. In further support of a potential pathophysiological role of Cables1, the expression level of Cables1 is tightly associated with p21 in both cancer cell lines and human lung cancer patient tumor samples. Together, these results suggest Cables1 as a novel p21 regulator through maintaining p21 stability and support the model that the tumor-suppressive function of Cables1 occurs at least in part through enhancing the tumor-suppressive activity of p21.

  20. Efficacy of soap and water and alcohol-based hand-rub preparations against live H1N1 influenza virus on the hands of human volunteers.

    Science.gov (United States)

    Grayson, M Lindsay; Melvani, Sharmila; Druce, Julian; Barr, Ian G; Ballard, Susan A; Johnson, Paul D R; Mastorakos, Tasoula; Birch, Christopher

    2009-02-01

    Although pandemic and avian influenza are known to be transmitted via human hands, there are minimal data regarding the effectiveness of routine hand hygiene (HH) protocols against pandemic and avian influenza. Twenty vaccinated, antibody-positive health care workers had their hands contaminated with 1 mL of 10(7) tissue culture infectious dose (TCID)(50)/0.1 mL live human influenza A virus (H1N1; A/New Caledonia/20/99) before undertaking 1 of 5 HH protocols (no HH [control], soap and water hand washing [SW], or use of 1 of 3 alcohol-based hand rubs [61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine solution, or 70% isopropanol plus 0.5% chlorhexidine solution]). H1N1 concentrations were assessed before and after each intervention by viral culture and real-time reverse-transcriptase polymerase chain reaction (PCR). The natural viability of H1N1 on hands for >60 min without HH was also assessed. There was an immediate reduction in culture-detectable and PCR-detectable H1N1 after brief cutaneous air drying--14 of 20 health care workers had H1N1 detected by means of culture (mean reduction, 10(3-4) TCID(50)/0.1 mL), whereas 6 of 20 had no viable H1N1 recovered; all 20 health care workers had similar changes in PCR test results. Marked antiviral efficacy was noted for all 4 HH protocols, on the basis of culture results (14 of 14 had no culturable H1N1; (P< .002) and PCR results (P< .001; cycle threshold value range, 33.3-39.4), with SW statistically superior (P< .001) to all 3 alcohol-based hand rubs, although the actual difference was only 1-100 virus copies/microL. There was minimal reduction in H1N1 after 60 min without HH. HH with SW or alcohol-based hand rub is highly effective in reducing influenza A virus on human hands, although SW is the most effective intervention. Appropriate HH may be an important public health initiative to reduce pandemic and avian influenza transmission.