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.)

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 ...

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...

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 ...

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...

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.

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

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...

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 ...

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 ...

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.

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

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.

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

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

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.

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 .

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

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

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.

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.

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

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

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

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

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

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.

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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.

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

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

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

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.

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

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

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

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

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

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

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

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

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 ...

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 ...

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 ...

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.

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.

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.

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

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

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

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

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.

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

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 ...

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 ...

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 ...

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 ...

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 ...

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...

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 ...

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 ...

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.

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.

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.

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

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

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

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 ...

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 ...

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

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

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.

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.

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.

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

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

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.

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

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)

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.

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

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.

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

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.

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.)

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.

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.

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.

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.

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.

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.

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.

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.

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...

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.

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.

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.

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

[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

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.

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.

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.

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

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.

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

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.

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

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

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

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.

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.

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

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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

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

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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.

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

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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.

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

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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.

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....

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

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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.

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

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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.

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.

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...

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

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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.

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

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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.

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.

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.

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

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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.

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

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

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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.

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.

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

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.

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.

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.

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.

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

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.

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

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

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

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.

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 -

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

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

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.

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.

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...

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.

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)....

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

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.

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.

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.

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

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...

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.

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.

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.

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

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*}

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

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

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.

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.

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 ...

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.

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.

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.)

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

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

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.

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 .

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

Lifescience Database Archive (English)

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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.

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

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

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 ...

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

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.

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)

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 ...

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.

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...

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

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.

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.

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

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

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

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.)

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.

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...

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.

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

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

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.

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.

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

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

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.

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

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

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.

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.

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

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

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.

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

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.

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...

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.

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.)

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.

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

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

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.

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

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.

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.

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...

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

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