Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation.

Science.gov (United States)

Ambhore, Nilesh Sudhakar; Katragadda, Rathnavali; Raju Kalidhindi, Rama Satyanarayana; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S; Sathish, Venkatachalem

2018-04-20

Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estrogen receptor (ER) expression increases in asthmatic human ASM; however, very limited data are available regarding differential roles of ERα vs. ERβ isoforms in human ASM cell proliferation. In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Western blot analysis. Gene and protein expression of cell cycle-related antigens (PCNA and Ki67) and C/EBP were measured by RT-PCR and Western analysis, along with cell signaling proteins. PDGF significantly increased ASM proliferation in non-asthmatic and asthmatic cells. Treatment with PPT showed no significant effect on PDGF-induced proliferation, whereas WAY interestingly suppressed proliferation via inhibition of ERK1/2, Akt, and p38 signaling. PDGF-induced gene expression of PCNA, Ki67 and C/EBP in human ASM was significantly lower in cells pre-treated with WAY. Furthermore, WAY also inhibited PDGF-activated PCNA, C/EBP, cyclin-D1, and cyclin-E. Overall, we demonstrate ER isoform-specific signaling in the context of ASM proliferation. Activation of ERβ can diminish remodeling in human ASM by inhibiting pro-proliferative signaling pathways

Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner.

Science.gov (United States)

Hultsch, T; Müller, K D; Meingassner, J G; Grassberger, M; Schopf, R E; Knop, J

1998-09-01

Mast cells play an important role in the pathological development of many inflammatory and allergic diseases and inhibition of mast cell activation is a potential target for therapeutic intervention. Therefore, the effect of the novel ascomycin macrolactam derivative SDZ ASM 981 on Fc epsilonRI-mediated activation of rat basophilic leukemia (RBL) cells, as a model for mast cell activation, was investigated. First, the ability to inhibit different mast cell immunophilins in vitro was tested. Using recombinant macrophilin-12 (FKBP-12), inhibition of rotamase activity with an IC50 of approximately 6 nM was observed. The rotamase activity of cyclophilin A (18 kDa) was not affected. Secondly, the effect of SDZ ASM 981 on Fc epsilonRI-mediated mast cell activation was investigated in the RBL cell model. SDZ ASM 981 inhibited exocytosis of preformed mediators (e.g. serotonin) with an IC50 of approximately 30 nM. Transcription and release of newly synthesized mediators (e.g. TNF-alpha) was inhibited with an IC50 of approximately 100 nM. The inhibitory effect of SDZ ASM 981 was antagonized by rapamycin. We conclude that SDZ ASM 981 is a potent inhibitor of Fc epsilonRI-mediated activation of mast cells in vitro. The mechanism of action involves formation of (calcineurin) inhibitory complexes with macrophilins. We suggest that this inhibitory action on mast cells might contribute to the antiinflammatory effect of SDZ ASM 981 observed in vivo (e.g. in aptopic dermatitis and psoriasis).

Accelerator System Model (ASM) user manual with physics and engineering model documentation. ASM version 1.0

International Nuclear Information System (INIS)

1993-07-01

The Accelerator System Model (ASM) is a computer program developed to model proton radiofrequency accelerators and to carry out system level trade studies. The ASM FORTRAN subroutines are incorporated into an intuitive graphical user interface which provides for the open-quotes constructionclose quotes of the accelerator in a window on the computer screen. The interface is based on the Shell for Particle Accelerator Related Codes (SPARC) software technology written for the Macintosh operating system in the C programming language. This User Manual describes the operation and use of the ASM application within the SPARC interface. The Appendix provides a detailed description of the physics and engineering models used in ASM. ASM Version 1.0 is joint project of G. H. Gillespie Associates, Inc. and the Accelerator Technology (AT) Division of the Los Alamos National Laboratory. Neither the ASM Version 1.0 software nor this ASM Documentation may be reproduced without the expressed written consent of both the Los Alamos National Laboratory and G. H. Gillespie Associates, Inc

76 FR 36231 - American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases

Science.gov (United States)

2011-06-21

...The NRC is amending its regulations to incorporate by reference the 2005 Addenda (July 1, 2005) and 2006 Addenda (July 1, 2006) to the 2004 ASME Boiler and Pressure Vessel Code, Section III, Division 1; 2007 ASME Boiler and Pressure Vessel Code, Section III, Division 1, 2007 Edition (July 1, 2007), with 2008a Addenda (July 1, 2008); 2005 Addenda (July 1, 2005) and 2006 Addenda (July 1, 2006) to the 2004 ASME Boiler and Pressure Vessel Code, Section XI, Division 1; 2007 ASME Boiler and Pressure Vessel Code, Section XI, Division 1, 2007 Edition (July 1, 2007), with 2008a Addenda (July 1, 2008); and 2005 Addenda, ASME OMa Code-2005 (approved July 8, 2005) and 2006 Addenda, ASME OMb Code-2006 (approved July 6, 2006) to the 2004 ASME Code for Operation and Maintenance of Nuclear Power Plants (OM Code). The NRC is also incorporating by reference (with conditions on their use) ASME Boiler and Pressure Vessel Code Case N-722-1, ``Additional Examinations for PWR Pressure Retaining Welds in Class 1 Components Fabricated with Alloy 600/82/182 Materials, Section XI, Division 1,'' Supplement 8, ASME approval date: January 26, 2009, and ASME Boiler and Pressure Vessel Code Case N-770-1, ``Alternative Examination Requirements and Acceptance Standards for Class 1 PWR Piping and Vessel Nozzle Butt Welds Fabricated With UNS N06082 or UNS W86182 Weld Filler Material With or Without Application of Listed Mitigation Activities, Section XI, Division 1,'' ASME approval date: December 25, 2009.

Accelerator System Model (ASM) user manual with physics and engineering model documentation. ASM version 1.0

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-07-01

The Accelerator System Model (ASM) is a computer program developed to model proton radiofrequency accelerators and to carry out system level trade studies. The ASM FORTRAN subroutines are incorporated into an intuitive graphical user interface which provides for the {open_quotes}construction{close_quotes} of the accelerator in a window on the computer screen. The interface is based on the Shell for Particle Accelerator Related Codes (SPARC) software technology written for the Macintosh operating system in the C programming language. This User Manual describes the operation and use of the ASM application within the SPARC interface. The Appendix provides a detailed description of the physics and engineering models used in ASM. ASM Version 1.0 is joint project of G. H. Gillespie Associates, Inc. and the Accelerator Technology (AT) Division of the Los Alamos National Laboratory. Neither the ASM Version 1.0 software nor this ASM Documentation may be reproduced without the expressed written consent of both the Los Alamos National Laboratory and G. H. Gillespie Associates, Inc.

MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells.

Directory of Open Access Journals (Sweden)

Mythili Dileepan

Full Text Available Airway smooth muscle (ASM cells play a critical role in the pathophysiology of asthma due to their hypercontractility and their ability to proliferate and secrete inflammatory mediators. microRNAs (miRNAs are gene regulators that control many signaling pathways and thus serve as potential therapeutic alternatives for many diseases. We have previously shown that miR-708 and miR-140-3p regulate the MAPK and PI3K signaling pathways in human ASM (HASM cells following TNF-α exposure. In this study, we investigated the regulatory effect of these miRNAs on other asthma-related genes. Microarray analysis using the Illumina platform was performed with total RNA extracted from miR-708 (or control miR-transfected HASM cells. Inhibition of candidate inflammation-associated gene expression was further validated by qPCR and ELISA. The most significant biologic functions for the differentially expressed gene set included decreased inflammatory response, cytokine expression and signaling. qPCR revealed inhibition of expression of CCL11, CXCL10, CCL2 and CXCL8, while the release of CCL11 was inhibited in miR-708-transfected cells. Transfection of cells with miR-140-3p resulted in inhibition of expression of CCL11, CXCL12, CXCL10, CCL5 and CXCL8 and of TNF-α-induced CXCL12 release. In addition, expression of RARRES2, CD44 and ADAM33, genes known to contribute to the pathophysiology of asthma, were found to be inhibited in miR-708-transfected cells. These results demonstrate that miR-708 and miR-140-3p exert distinct effects on inflammation-associated gene expression and biological function of ASM cells. Targeting these miRNA networks may provide a novel therapeutic mechanism to down-regulate airway inflammation and ASM proliferation in asthma.

TRAIL death receptor 4 signaling via lysosome fusion and membrane raft clustering in coronary arterial endothelial cells: evidence from ASM knockout mice.

Science.gov (United States)

Li, Xiang; Han, Wei-Qing; Boini, Krishna M; Xia, Min; Zhang, Yang; Li, Pin-Lan

2013-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 4 (DR4), have been implicated in the development of endothelial dysfunction and atherosclerosis. However, the signaling mechanism mediating DR4 activation leading to endothelial injury remains unclear. We recently demonstrated that ceramide production via hydrolysis of membrane sphingomyelin by acid sphingomyelinase (ASM) results in membrane raft (MR) clustering and the formation of important redox signaling platforms, which play a crucial role in amplifying redox signaling in endothelial cells leading to endothelial dysfunction. The present study aims to investigate whether TRAIL triggers MR clustering via lysosome fusion and ASM activation, thereby conducting transmembrane redox signaling and changing endothelial function. Using confocal microscopy, we found that TRAIL induced MR clustering and co-localized with DR4 in coronary arterial endothelial cells (CAECs) isolated from wild-type (Smpd1 (+/+)) mice. Furthermore, TRAIL triggered ASM translocation, ceramide production, and NADPH oxidase aggregation in MR clusters in Smpd1 ( +/+ ) CAECs, whereas these observations were not found in Smpd1 (-/-) CAECs. Moreover, ASM deficiency reduced TRAIL-induced O(2) (-[Symbol: see text]) production in CAECs and abolished TRAIL-induced impairment on endothelium-dependent vasodilation in small resistance arteries. By measuring fluorescence resonance energy transfer, we found that Lamp-1 (lysosome membrane marker protein) and ganglioside G(M1) (MR marker) were trafficking together in Smpd1 (+/+) CAECs, which was absent in Smpd1 (-/-) CAECs. Consistently, fluorescence imaging of living cells with specific lysosome probes demonstrated that TRAIL-induced lysosome fusion with membrane was also absent in Smpd1 (-/-) CAECs. Taken together, these results suggest that ASM is essential for TRAIL-induced lysosomal trafficking, membrane fusion and formation of MR redox signaling platforms

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

Science.gov (United States)

Luger, T; Van Leent, E J; Graeber, M; Hedgecock, S; Thurston, M; Kandra, A; Berth-Jones, J; Bjerke, J; Christophers, E; Knop, J; Knulst, A C; Morren, M; Morris, A; Reitamo, S; Roed-Petersen, J; Schoepf, E; Thestrup-Pedersen, K; Van Der Valk, P G; Bos, J D

2001-04-01

SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and

AIS ASM Operational Integration Plan

Science.gov (United States)

2013-08-01

Rack mount computer AIS Radio Interface Ethernet Switch 192.168.0.x Firewall Cable Modem 192.168.0.1 VTS Accred. Boundary AIS ASM Operational... AIS ASM Operational Integration Plan Distribution Statement A: Approved for public release; distribution is unlimited. August 2013 Report No...CD-D-07-15 AIS ASM Operational Integration Plan ii UNCLAS//Public | CG-926 R&DC | I. Gonin, et al. | Public August 2013 N O T I C

CONAGT's place in ASME's centennial year

International Nuclear Information System (INIS)

Miller, W.H. Jr.

1985-01-01

A status report on ASME's Committee on Nuclear Air and Gas Treatment (CONAGT) is presented. This year ASME celebrates its centennial while CONAGT issues its first code sections covering fans, blowers, and refrigeration equipment. Significant code related CONAGT activities are covered as well as an explanation of CONAGT's place in the ASME organization

Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma.

Science.gov (United States)

Teoh, Chun Ming; Tam, John Kit Chung; Tran, Thai

2012-01-01

Airway hyperresponsiveness (AHR) is one of the cardinal features of asthma. Contraction of airway smooth muscle (ASM) cells that line the airway wall is thought to influence aspects of AHR, resulting in excessive narrowing or occlusion of the airway. ASM contraction is primarily controlled by agonists that bind G protein-coupled receptor (GPCR), which are expressed on ASM. Integrins also play a role in regulating ASM contraction signaling. As therapies for asthma are based on symptom relief, better understanding of the crosstalk between GPCRs and integrins holds good promise for the design of more effective therapies that target the underlying cellular and molecular mechanism that governs AHR. In this paper, we will review current knowledge about integrins and GPCRs in their regulation of ASM contraction signaling and discuss the emerging concept of crosstalk between the two and the implication of this crosstalk on the development of agents that target AHR.

Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

International Nuclear Information System (INIS)

Pei, Qing-Mei; Jiang, Ping; Yang, Min; Qian, Xue-Jiao; Liu, Jiang-Bo; Kim, Sung-Ho

2016-01-01

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

Energy Technology Data Exchange (ETDEWEB)

Pei, Qing-Mei, E-mail: 34713316@qq.com [Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin (China); Jiang, Ping, E-mail: jiangping@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Yang, Min, E-mail: YangMin@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Qian, Xue-Jiao, E-mail: qianxuejiao@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Liu, Jiang-Bo, E-mail: LJB1984@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China)

2016-10-01

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

75 FR 24323 - American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases

Science.gov (United States)

2010-05-04

...The NRC proposes to amend its regulations to incorporate by reference the 2005 Addenda through 2008 Addenda of Section III, Division 1, and the 2005 Addenda through 2008 Addenda of Section XI, Division 1, of the ASME Boiler and Pressure Vessel Code (ASME B&PV Code); and the 2005 Addenda and 2006 Addenda of the ASME Code for Operation and Maintenance of Nuclear Power Plants (ASME OM Code). The NRC also proposes to incorporate by reference ASME Code Case N-722-1, ``Additional Examinations for PWR Pressure Retaining Welds in Class 1 Components Fabricated With Alloy 600/82/182 Materials Section XI, Division 1,'' and Code Case N-770, ``Alternative Examination Requirements and Acceptance Standards for Class 1 PWR [Pressurized- Water Reactor] Piping and Vessel Nozzle Butt Welds Fabricated with UNS N06082 or UNS W86182 Weld Filler Material with or without Application of Listed Mitigation Activities.''

Nondestructive testing standards and the ASME code

International Nuclear Information System (INIS)

Spanner, J.C.

1991-04-01

Nondestructive testing (NDT) requirements and standards are an important part of the ASME Boiler and Pressure Vessel Code. In this paper, the evolution of these requirements and standards is reviewed in the context of the unique technical and legal stature of the ASME Code. The coherent and consistent manner by which the ASME Code rules are organized is described, and the interrelationship between the various ASME Code sections, the piping codes, and the ASTM Standards is discussed. Significant changes occurred in ASME Sections 5 and 11 during the 1980s, and these are highlighted along with projections and comments regarding future trends and changes in these important documents. 4 refs., 8 tabs

The ASME Code today -- Challenges, threats, opportunities

International Nuclear Information System (INIS)

Canonico, D.A.

1995-01-01

Since its modest beginning as a single volume in 1914 the ASME Code, or some of its parts, is recognized today in 48 of the United States and all providence's of Canada. The ASME Code today is composed of 25 books including two Code Case books. These books cover the new construction of boilers and pressure vessels and the new construction and In-Service-Inspection of Nuclear Power Plant components. The ASME accredits all manufacturers of boilers and pressure vessels built to the ASME Code. There are approximately 7650 symbol stamps issued throughout the world. Over 23% of the symbol stamps have been issued outside the USA and Canada. The challenge to the ASME Code is to be accepted as the world standard for pressure boundary components. There are activities underway to achieve that goal. The ASME Code is being revised to make it a more friendly document to entities outside of North America. To achieve that end there are specific tasks underway which are described here

Globalization of ASME Nuclear Codes and Standards

International Nuclear Information System (INIS)

Swayne, Rick; Erler, Bryan A.

2006-01-01

With the globalization of the nuclear industry, it is clear that the reactor suppliers are based in many countries around the world (such as United States, France, Japan, Canada, South Korea, South Africa) and they will be marketing their reactors to many countries around the world (such as US, China, South Korea, France, Canada, Finland, Taiwan). They will also be fabricating their components in many different countries around the world. With this situation, it is clear that the requirements of ASME Nuclear Codes and Standards need to be adjusted to accommodate the regulations, fabricating processes, and technology of various countries around the world. It is also very important for the American Society of Mechanical Engineers (ASME) to be able to assure that products meeting the applicable ASME Code requirements will provide the same level of safety and quality assurance as those products currently fabricated under the ASME accreditation process. To do this, many countries are in the process of establishing or changing their regulations, and it is important for ASME to interface with the appropriate organizations in those countries, in order to ensure there is effective use of ASME Codes and standards around the world. (authors)

ASM observations of X-ray flares from 4U 0115+63 and ASM 1354-64.

Science.gov (United States)

Tsunemi, H.; Kitamoto, S.

The authors report two X-ray flares detected with the All Sky Monitor (ASM) on board the GINGA satellite. One is from the recurrent X-ray pulsar 4U 0115+63 and the other is from the probable recurrent X-ray nova named ASM 1354-64. The maximum intensity for 4U 0115+63 was 180 mCrab and its duration was at least 22 days. Its spectrum was hard and resembled those of X-ray pulsars. The maximum intensity of ASM 1354-64 was 300 mCrab. It faded down below the detection limit at the end of August 1987. Its spectrum was soft and was similar to those of black hole candidates.

Technical Challenge and Demonstration of Advanced Solution Monitoring and Measurement System (ASMS)

International Nuclear Information System (INIS)

Takaya, A.; Mukai, Y.; Nakamura, H.; Hosoma, T.; Yoshimoto, K.; Tamura, T.; Iwamoto, T.

2010-01-01

JNFL and JAEA have collaboratively started to develop an Advanced Solution Measurement and monitoring System (ASMS) as a part of technical challenge intended for next generation safeguards NDA equipment. After we completed feasibility study by using small detectors, the second stage of ASMS has installed into PCDF tank located in a cell, and then tested and calibrated by Pu nitrate solution experimentally. There was no experience measuring around 50kg Pu inventory directly, so it was very challenging work. The conventional SMMS (Solution Monitoring and Measurement System) that is composed of precision manometers acquires density, level and temperature of solution, so that the sampling and analysis are essential to obtain the nuclear material amount in the tank. The SMMS has two weak points on verification and monitoring of the nuclear material flow and inventory; (1) Direct measurement of the inventory cannot be done, (2) Solution rework and reagent adjustment operation in actual plant will make miss-interpretation on the monitoring evaluation. The purpose of ASMS development is to establish quantitative plutonium mass measurement technique directly by NDA of high concentrated pure plutonium nitrate solution and monitoring capability for solution transfers in a process. The merits of ASMS are considered below; (1) Provide direct Pu measurement and continuous monitoring capability, (2) Eliminate sampling and analysis at IIV, (3) Reduce unmeasured inventory. The target of the measurement uncertainty of ASMS is set less than 6% (1sigma) which is equivalent to meet the detection level of the partial defect at IIV by NDA. Known-alpha coincidence counting technique is applied to the ASMS, which is similar to the NDAs for MOX powder as a principle measurement technique. Especially, three following points are key techniques to establish ASMS. (1) Pre-determination of plutonium isotopic composition because it impacts alpha and rho-zero values to obtain multiplication

Index to place of publication of ASME Papers, 1978--1988

International Nuclear Information System (INIS)

Youngen, G.K.

1990-06-01

This index is a list of American Society of Mechanical Engineers (ASME) Papers that are reprinted in the ASME Transactions series of journals. ASME Papers are often cited only by their paper number, making it difficult to determine if the article has ever appeared in print in the journal literature. This index will be useful for tracking down those papers published as journal articles by the ASME. It will also serve as a guide for retention for subscribers to the ASME Papers and Transaction Series. Paper numbers that appear in the journals may be weeded from the collection of ASME Papers

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

NARCIS (Netherlands)

Luger, T.; Leent, E.J. van; Graeber, M.; Hedgecock, S.; Thurston, M.; Kandra, A.; Berth-Jones, J.; Bjerke, J.; Christophers, E.; Knop, J.; Knulst, A.C.; Morren, M.; Morris, A.; Reitamo, S.; Roed-Petersen, J.; Schoepf, E.; Thestrup-Pedersen, K.; Valk, P.G.M. van der; Bos, J.D.

2001-01-01

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis

NARCIS (Netherlands)

Luger, T; Van Leent, EJM; Graeber, M; Hedgecock, S; Thurston, M; Kandra, A; Berth-Jones, J; Bjerke, J; Christophers, E; Knulst, AC; Morren, M; Morris, A; Reitamo, S; Roed-Petersen, J; Schoepf, E; Thestrup-Pedersen, K; van der Valk, P. G. M.; Bos, JD

Background SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. Objectives This study was: designed to determine

Activated sludge model No. 2d, ASM2d

DEFF Research Database (Denmark)

Henze, M.

1999-01-01

The Activated Sludge Model No. 2d (ASM2d) presents a model for biological phosphorus removal with simultaneous nitrification-denitrification in activated sludge systems. ASM2d is based on ASM2 and is expanded to include the denitrifying activity of the phosphorus accumulating organisms (PAOs......). This extension of ASM2 allows for improved modeling of the processes, especially with respect to the dynamics of nitrate and phosphate. (C) 1999 IAWQ Published by Elsevier Science Ltd. All rights reserved....

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis

NARCIS (Netherlands)

Luger, T.; van Leent, E. J.; Graeber, M.; Hedgecock, S.; Thurston, M.; Kandra, A.; Berth-Jones, J.; Bjerke, J.; Christophers, E.; Knop, J.; Knulst, A. C.; Morren, M.; Morris, A.; Reitamo, S.; Roed-Petersen, J.; Schoepf, E.; Thestrup-Pedersen, K.; van der Valk, P. G.; Bos, J. D.

2001-01-01

SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. This study was designed to determine the safety and efficacy

The DNA methylome of human peripheral blood mononuclear cells.

Directory of Open Access Journals (Sweden)

Yingrui Li

2010-11-01

Full Text Available DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand, we report a comprehensive (92.62% methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC from the same Asian individual whose genome was deciphered in the YH project. PBMC constitute an important source for clinical blood tests world-wide. We found that 68.4% of CpG sites and 80% displayed allele-specific expression (ASE. These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.

An example of a component replacement when applying ASME N509 and ASME N510 to older ventilation systems

International Nuclear Information System (INIS)

Arndt, T.E.

1994-06-01

This paper presents an example of a component replacement (electric heater) when installed in an older ventilation system that was constructed before the issuance of ASME N509 and N510. Many of the existing ventilation systems at the Hanford Site were designed, fabricated, and installed before the issuance of ASME N509 and N510. Requiring the application of these codes to existing ventilation systems presents challenges to the engineer when design changes are needed. Although it may seem that the application of ASME N509 or N510 may be a hindrance at times, this does not need to occur. Proper preparation at the start of project or design modifications can minimize frustration to the engineer when it is judged that portions of ASME N509 and N510 do not apply in a particular application

Safety Analysis Report for the KRI-ASM Transport Package

Energy Technology Data Exchange (ETDEWEB)

Bang, K. S.; Lee, J. C.; Kim, D. H.; Park, H. Y.; Kim, J. B.; Kim, H. J.; Seo, K. S

2005-11-15

Safety evaluation for the KRI-ASM transport package to transport safely I-131, which is produced at HANARO research reactor in KAERI, was carried out. In the safety analyses results for the KRI-ASM transport package, all the maximum stresses as well as the maximum temperature of the surface are lower than their allowable limits. The safety tests were performed by using the test model of the KRI-ASM transport package. Leak Test was performed after drop test and penetration test, the measured leakage rate was lower than allowable leakage rate. It is revealed that the containment integrity of the KRI-ASM transport package is maintained. Therefore, it shows that the integrity of the KRI-ASM transport package is well maintained.

ASME Code requirements for multi-canister overpack design and fabrication

International Nuclear Information System (INIS)

SMITH, K.E.

1998-01-01

The baseline requirements for the design and fabrication of the MCO include the application of the technical requirements of the ASME Code, Section III, Subsection NB for containment and Section III, Subsection NG for criticality control. ASME Code administrative requirements, which have not historically been applied at the Hanford site and which have not been required by the US Nuclear Regulatory Commission (NRC) for licensed spent fuel casks/canisters, were not invoked for the MCO. As a result of recommendations made from an ASME Code consultant in response to DNFSB staff concerns regarding ASME Code application, the SNF Project will be making the following modifications: issue an ASME Code Design Specification and Design Report, certified by a Registered Professional Engineer; Require the MCO fabricator to hold ASME Section III or Section VIII, Division 2 accreditation; and Use ASME Authorized Inspectors for MCO fabrication. Incorporation of these modifications will ensure that the MCO is designed and fabricated in accordance with the ASME Code. Code Stamping has not been a requirement at the Hanford site, nor for NRC licensed spent fuel casks/canisters, but will be considered if determined to be economically justified

International Accreditation of ASME Codes and Standards

International Nuclear Information System (INIS)

Green, Mervin R.

1989-01-01

ASME established a Boiler Code Committee to develop rules for the design, fabrication and inspection of boilers. This year we recognize 75 years of that Code and will publish a history of that 75 years. The first Code and subsequent editions provided for a Code Symbol Stamp or mark which could be affixed by a manufacturer to a newly constructed product to certify that the manufacturer had designed, fabricated and had inspected it in accordance with Code requirements. The purpose of the ASME Mark is to identify those boilers that meet ASME Boiler and Pressure Vessel Code requirements. Through thousands of updates over the years, the Code has been revised to reflect technological advances and changing safety needs. Its scope has been broadened from boilers to include pressure vessels, nuclear components and systems. Proposed revisions to the Code are published for public review and comment four times per year and revisions and interpretations are published annually; it's a living and constantly evolving Code. You and your organizations are a vital part of the feedback system that keeps the Code alive. Because of this dynamic Code, we no longer have columns in newspapers listing boiler explosions. Nevertheless, it has been argued recently that ASME should go further in internationalizing its Code. Specifically, representatives of several countries, have suggested that ASME delegate to them responsibility for Code implementation within their national boundaries. The question is, thus, posed: Has the time come to franchise responsibility for administration of ASME's Code accreditation programs to foreign entities or, perhaps, 'institutes.' And if so, how should this be accomplished?

Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency.

Science.gov (United States)

Acuña, Mariana; Castro-Fernández, Víctor; Latorre, Mauricio; Castro, Juan; Schuchman, Edward H; Guixé, Victoria; González, Mauricio; Zanlungo, Silvana

2016-10-21

Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three-dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site. However, energy function calculations using statistical potentials indicate that the mutation causes a decrease in ASM stability. Therefore, we investigated the functional effect of the p.Ala359Asp mutation in ASM expression, secretion, localization and activity in human fibroblasts. We found a 3.8% residual ASM activity compared to the wild-type enzyme, without changes in the other parameters evaluated. These results support the hypothesis that the p.Ala359Asp mutation causes structural alterations in the hydrophobic environment where ASM is located, decreasing its enzymatic activity. A similar effect was observed in other previously described NPDB mutations located outside the active site of the enzyme. This work shows the first full size ASM mutant model describe at date, providing a complete analysis of the structural and functional effects of the p.Ala359Asp mutation over the stability and activity of the enzyme. Copyright © 2016 Elsevier Inc. All rights reserved.

Temporal Deductive Verification of Basic ASM Models

OpenAIRE

Daho, Hocine El-Habib; University of Oran; Benhamamouch, Djillali; University of Oran

2010-01-01

Abstract State Machines (ASMs, for short) provide a practical new computational model which has been applied in the area of software engineering for systems design and analysis. However, reasoning about ASM models occurs, not within a formal deductive system, but basically in the classical informal proofs style of mathematics. Several formal verification approaches for proving correctness of ASM models have been investigated. In this paper we consider the use of the TLA+logic for the deductive...

Meeting the difficulties of an ASME calibration for pipe welds

Energy Technology Data Exchange (ETDEWEB)

Ginzel, E., E-mail: eginzel@mri.on.ca [Materials Research Inst., Waterloo, Ontario (Canada); Ginzel, R.; Buchholz, J., E-mail: rginzel@eclipsescientific.com [Eclipse Scientific, Waterloo, Ontario (Canada)

2013-11-15

The American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel code Section V deals with Non-Destructive Testing (NDT). In North America the use of ASME Sec. V is not always limited to just ASME regulated projects. Even such seemingly unrelated Standards as CSA Z662 (the Canadian construction standard for Oil and Gas Pipeline Systems) references this document for some aspects of the NDT. ASME has several codes that are dedicated to piping welds, for example ASME 31.1, 31.3 and 31.8. All of them reference back to ASME Section V Article 4 for the accepted techniques to use when UT is the examination option, but sometimes ASME is not very helpful. As they try to leave options open in one area they close the doors in others, or so it seems when reading the clauses as mandatory where you see the word 'shall'. This paper will attempt to layout the issues with pipe weld inspections as per Article 4, 2011 edition. Like all other codes and standards, ASME is a regulated standard that is regularly reviewed and updated, and one must be careful to reference the year of the edition being used. For the purposes of this paper we have used the 2010/11 edition. (author)

Meeting the difficulties of an ASME calibration for pipe welds

International Nuclear Information System (INIS)

Ginzel, E.; Ginzel, R.; Buchholz, J.

2013-01-01

The American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel code Section V deals with Non-Destructive Testing (NDT). In North America the use of ASME Sec. V is not always limited to just ASME regulated projects. Even such seemingly unrelated Standards as CSA Z662 (the Canadian construction standard for Oil and Gas Pipeline Systems) references this document for some aspects of the NDT. ASME has several codes that are dedicated to piping welds, for example ASME 31.1, 31.3 and 31.8. All of them reference back to ASME Section V Article 4 for the accepted techniques to use when UT is the examination option, but sometimes ASME is not very helpful. As they try to leave options open in one area they close the doors in others, or so it seems when reading the clauses as mandatory where you see the word 'shall'. This paper will attempt to layout the issues with pipe weld inspections as per Article 4, 2011 edition. Like all other codes and standards, ASME is a regulated standard that is regularly reviewed and updated, and one must be careful to reference the year of the edition being used. For the purposes of this paper we have used the 2010/11 edition. (author)

An example of a component replacement when applying ASME N509 and ASME N510 to older ventilation systems

Energy Technology Data Exchange (ETDEWEB)

Arndt, T.E. [Westinghouse Hanford Company, Richland, WA (United States)

1995-02-01

This paper presents an example of a component replacement (electric heater) when installed in an older ventilation system that was constructed before the issuance of ASME N509{sup 1} and N510{sup 2}. Many of the existing ventilation systems at the Hanford Site were designed, fabricated, and installed before the issuance of ASME N509{sup 1} and N510{sup 2}. Requiring the application of these codes to existing ventilation systems presents challenges to the engineer when design changes are needed. Although it may seem that the application of ASME N509{sup 1} or N510{sup 2} may be a hindrance at times, this does not need to occur. Proper preparation at the start of project or design modifications can minimize frustration to the engineer when it is judged that portions of ASME N509{sup 1} and N510{sup 2} do not apply in a particular application.

Anti-EGFR Antibody Efficiently and Specifically Inhibits Human TSC2−/− Smooth Muscle Cell Proliferation. Possible Treatment Options for TSC and LAM

Science.gov (United States)

Lesma, Elena; Grande, Vera; Ancona, Silvia; Carelli, Stephana; Di Giulio, Anna Maria; Gorio, Alfredo

2008-01-01

Background Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2−/− ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2−/− ASM cell proliferation is EGF-dependent. Methods and Findings Effects of EGF on proliferation of TSC2−/− ASM cells and TSC2−/− ASM cells transfected with TSC2 gene were determined. In contrast to TSC2−/− ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2−/− ASM cells. Exposure of TSC2−/− ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2−/− cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2−/− ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2−/− ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. Conclusion Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC−/− ASM cells, and such EGF-dependency is the result of the lack of tuberin. PMID:18958173

Neurospora crassa ASM-1 complements the conidiation defect in a stuA mutant of Aspergillus nidulans.

Science.gov (United States)

Chung, Dawoon; Upadhyay, Srijana; Bomer, Brigitte; Wilkinson, Heather H; Ebbole, Daniel J; Shaw, Brian D

2015-01-01

Aspergillus nidulans StuA and Neurospora crassa ASM-1 are orthologous APSES (ASM-1, PHD1, SOK2, Efg1, StuA) transcription factors conserved across a diverse group of fungi. StuA and ASM-1 have roles in asexual (conidiation) and sexual (ascospore formation) development in both organisms. To address the hypothesis that the last common ancestor of these diverse fungi regulated conidiation with similar genes, asm-1 was introduced into the stuA1 mutant of A. nidulans. Expression of asm-1 complemented defective conidiophore morphology and restored conidia production to wild type levels in stuA1. Expression of asm-1 in the stuA1 strain did not rescue the defect in sexual development. When the conidiation regulator AbaA was tagged at its C-terminus with GFP in A. nidulans, it localized to nuclei in phialides. When expressed in the stuA1 mutant, AbaA::GFP localized to nuclei in conidiophores but no longer was confined to phialides, suggesting that expression of AbaA in specific cell types of the conidiophore was conditioned by StuA. Our data suggest that the function in conidiation of StuA and ASM-1 is conserved and support the view that, despite the great morphological and ontogenic diversity of their condiphores, the last common ancestor of A. nidulans and N. crassa produced an ortholog of StuA that was involved in conidiophore development. © 2015 by The Mycological Society of America.

Review of ASME-NH Design Materials for Creep-Fatigue

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Kim, Jong Bum

2010-01-01

To review and recommend the candidate design materials for the Sodium-Cooled Fast Reactor, the material sensitivity evaluations by the comparison of design data between the ASME-NH materials were performed by using the SIE ASME-NH computer program implementing the material database of the ASME-NH. The design material data provided by the ASME-NH code are the elastic modulus and yield Strength, Time-Independent Allowable Stress Intensity value, time-dependent allowable stress intensity value, expected minimum stress-to rupture value, stress rupture Factors for weldment, isochronous stress-strain curves, and design fatigue curves. Among these, the data related with the creep-fatigue evaluation are investigated in this study

Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

NARCIS (Netherlands)

Burgess, J. K.; Ketheson, A.; Faiz, A.; Rempel, K. A. Limbert; Oliver, B. G.; Ward, J. P. T.; Halayko, A. J.

2018-01-01

Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness

Cisco ASM Router

CERN Multimedia

2001-01-01

One of the two "ASM/2-32EM" boxes installed in 1988, from "Cisco Systems Inc." - then an unknown 20-employee company in Menlo Park, California (USA). This is one of the first two Cisco boxes to appear in Switzerland, and possibly Europe. The 220v power supply was a special modification made for use at CERN. They supported IP address filtering, which seemed just what CERN needed to help protect the new Cray XMP-48 super computer from network hackers. The two ASM boxes were both routers and terminal servers. They protected a secure private Ethernet segment used by the Cray project, as well as providing secure terminal connections to that segment, including CERN's first dialback terminal service, which allowed Cray and CERN system analysts to work on the machine from home, using another Cisco feature called TACACS. (Kindly offered by B. Segal who discovered this company while at a Usenix Conference in Phoenix, Arizona in June 1987.)

Report on the Current Technical Issues on ASME Nuclear Code and Standard

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Lee, B. S.; Yoo, S. H.

2008-11-01

This report describes the analysis on the current revision movement related to the mechanical design issues of the U.S ASME nuclear code and standard. ASME nuclear mechanical design in this report is composed of the nuclear material, primary system, secondary system and high temperature reactor. This report includes the countermeasures based on the ASME Code meeting for current issues of each major field. KAMC(ASME Mirror Committee) of this project is willing to reflect a standpoint of the domestic nuclear industry on ASME nuclear mechanical design and play a technical bridge role for the domestic nuclear industry in ASME Codes application

Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

Science.gov (United States)

Ji, Yamei; Yang, Xin; Su, Huixia

2018-02-01

The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

ASME nuclear codes and standards risk management strategic planning

International Nuclear Information System (INIS)

Hill, Ralph S. III; Balkey, Kenneth R.; Erler, Bryan A.; Wesley Rowley, C.

2007-01-01

This paper is prepared in honor and in memory of the late Professor Emeritus Yasuhide Asada to recognize his contributions to ASME Nuclear Codes and Standards initiatives, particularly those related to risk-informed technology and System Based Code developments. For nearly two decades, numerous risk-informed initiatives have been completed or are under development within the ASME Nuclear Codes and Standards organization. In order to properly manage the numerous initiatives currently underway or planned for the future, the ASME Board on Nuclear Codes and Standards (BNCS) has an established Risk Management Strategic Plan (Plan) that is maintained and updated by the ASME BNCS Risk Management Task Group. This paper presents the latest approved version of the plan beginning with a background of applications completed to date, including the recent probabilistic risk assessment (PRA) standards developments for nuclear power plant applications. The paper discusses planned applications within ASME Nuclear Codes and Standards that will require expansion of the ASME PRA Standard to support new advanced light water reactor and next generation reactor developments, such as for high temperature gas-cooled reactors. Emerging regulatory developments related to risk-informed, performance- based approaches are summarized. A long-term vision for the potential development and evolution to a nuclear systems code that adopts a risk-informed approach across a facility life-cycle (design, construction, operation, maintenance, and closure) is also summarized. Finally, near term and long term actions are defined across the ASME Nuclear Codes and Standards organizations related to risk management, including related U.S. regulatory activities. (author)

AsmL Specification of a Ptolemy II Scheduler

DEFF Research Database (Denmark)

Lázaro Cuadrado, Daniel; Koch, Peter; Ravn, Anders Peter

2003-01-01

Ptolemy II is a tool that combines different computational models for simulation and design of embedded systems. AsmL is a software specification language based on the Abstract State Machine formalism. This paper reports on development of an AsmL model of the Synchronous Dataflow domain scheduler...

A user's perspective on the merits and shortcomings of ASME Section III

International Nuclear Information System (INIS)

Antaki, G.A.

1994-01-01

There are several aspects of Section III which when compared to process industry codes (ASME VIII, ASME B31.3, API, etc.) have proven to be a significant improvement in engineering practice. There are, however, other aspects of ASME III which have added to costs without clear benefits in safety or reliability. The authors present a user's perspective on some of the relative merits and shortcomings of the nuclear codes (ASME III and XI) compared to the process industry codes (such as ASME VIII, B31.3 and API)

Significant issues and changes for ANSI/ASME OM-1 1981, part 1, ASME OMc code-1994, and ASME OM Code-1995, Appendix I, inservice testing of pressure relief devices in light water reactor power plants

Energy Technology Data Exchange (ETDEWEB)

Seniuk, P.J.

1996-12-01

This paper identifies significant changes to the ANSI/ASME OM-1 1981, Part 1, and ASME Omc Code-1994 and ASME OM Code-1995, Appendix I, {open_quotes}Inservice Testing of Pressure Relief Devices in Light-Water Reactor Power Plants{close_quotes}. The paper describes changes to different Code editions and presents insights into the direction of the code committee and selected topics to be considered by the ASME O&M Working Group on pressure relief devices. These topics include scope issues, thermal relief valve issues, as-found and as-left set-pressure determinations, exclusions from testing, and cold setpoint bench testing. The purpose of this paper is to describe some significant issues being addressed by the O&M Working Group on Pressure Relief Devices (OM-1). The writer is currently the chair of OM-1 and the statements expressed herein represents his personal opinion.

Significant issues and changes for ANSI/ASME OM-1 1981, part 1, ASME OMc code-1994, and ASME OM Code-1995, Appendix I, inservice testing of pressure relief devices in light water reactor power plants

International Nuclear Information System (INIS)

Seniuk, P.J.

1996-01-01

This paper identifies significant changes to the ANSI/ASME OM-1 1981, Part 1, and ASME Omc Code-1994 and ASME OM Code-1995, Appendix I, open-quotes Inservice Testing of Pressure Relief Devices in Light-Water Reactor Power Plantsclose quotes. The paper describes changes to different Code editions and presents insights into the direction of the code committee and selected topics to be considered by the ASME O ampersand M Working Group on pressure relief devices. These topics include scope issues, thermal relief valve issues, as-found and as-left set-pressure determinations, exclusions from testing, and cold setpoint bench testing. The purpose of this paper is to describe some significant issues being addressed by the O ampersand M Working Group on Pressure Relief Devices (OM-1). The writer is currently the chair of OM-1 and the statements expressed herein represents his personal opinion

Application procedures and analysis examples of the SIE ASME-NH program

International Nuclear Information System (INIS)

Kim, Seok Hoon; Koo, G. H.; Kim, J. B.

2010-12-01

In this report, the design rule of the ASME-NH Code was briefly summarized and the application procedures of SIE ASME-NH program were analysed, the analysis examples were described. The SIE ASME-NH program was developed according to the ASME Code Section III Subsection NH rules to perform the primary stress limits, the accumulated inelastic strain limits and the creep fatigue damage evaluations in the structural design of nuclear power plants operating with high temperatures over creep temperature at normal operating conditions. In the analysis examples, the benchmark problem for the high temperature reactor vessel which was discussed in the SIE ASME-NH user's seminar was described. Also, the preliminary structural analysis of an Advanced Burner Test Reactor internal structure was described. Considering the load combinations of the various cycle types submitted from significant operating conditions, the integrity of a reactor internal structure was reviewed according to the stress and strain limits of the ASME-NH rules and the analysis and evaluation results were summarized

ASME nuclear codes and standards risk management strategic plan

International Nuclear Information System (INIS)

Balkey, Kenneth R.

2003-01-01

Over the past 15 years, several risk-informed initiatives have been completed or are under development within the ASME Nuclear Codes and Standards organization. In order to better manage the numerous initiatives in the future, the ASME Board on Nuclear Codes and Standards has recently developed and approved a Risk Management Strategic Plan. This paper presents the latest approved version of the plan beginning with a background of applications completed to date, including the recent issuance of the ASME Standard for Probabilistic Risk Assessment (PRA) for Nuclear Power Plant Applications. The paper discusses potential applications within ASME Nuclear Codes and Standards that may require expansion of the PRA Standard, such as for new generation reactors, or the development of new PRA Standards. A long-term vision for the potential development and evolution to a nuclear systems code that adopts a risk-informed approach across a facility life-cycle (design, construction, operation, maintenance, and closure) is summarized. Finally, near term and long term actions are defined across the ASME Nuclear Codes and Standards organizations related to risk management, and related U.S. regulatory activities are also summarized. (author)

Computer Program of SIE ASME-NH (Revision 1.0) Code

Energy Technology Data Exchange (ETDEWEB)

Koo, Gyeong Hoi; Lee, J. H

2008-01-15

In this report, the SIE ASME (Structural Integrity Evaluations by ASME-NH) (Revision 1.0), which has a computerized implementation of ASME Pressure Vessels and Piping Code Section III Subsection NH rules, is developed to apply to the next generation reactor design subjecting to the elevated temperature operations over 500 .deg. C and over 30 years design lifetime, and the user's manual for this program is described in detail.

Computer Program of SIE ASME-NH (Revision 1.0) Code

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Lee, J. H.

2008-01-01

In this report, the SIE ASME (Structural Integrity Evaluations by ASME-NH) (Revision 1.0), which has a computerized implementation of ASME Pressure Vessels and Piping Code Section III Subsection NH rules, is developed to apply to the next generation reactor design subjecting to the elevated temperature operations over 500 .deg. C and over 30 years design lifetime, and the user's manual for this program is described in detail

Recent development in the ASME O and M committee codes, standards, and guides

International Nuclear Information System (INIS)

Rowley, C.W.

1999-01-01

The ASME O and M Committee continues to expand and update its code, standards, and guides as contained in the ASME OM Code and the ASME OM Standards/Guides. This paper will describe recent changes to these two ASME documents, including technical inquiries, code cases, and the major reformat of the ASME OM Code 1998 Edition. Also two new Parts to the ASME OM S/G will be discussed: OM Part 23 and OM Part 24, which are close to being initially published. A third new Part to the ASME OM S/G has been authorized and has recently started to get organized: Part 26, 'Thermal Calibration of RTDs'. In addition this paper will describe the future plans for these two documents as provided in the O and M Committee Strategic Plan. (author)

Future direction of ASME nuclear codes and standards

International Nuclear Information System (INIS)

Ennis, Kevin; Sheehan, Mark E.

2003-01-01

While the nuclear power industry in the US is in a period of stasis, there continues to be a great deal of activity in the ASME nuclear standards development arena. As plants age, the need for new approaches in standardization changes with the changing needs of the industry. New tools are becoming available in the form of risk analysis, and this is finding its way into more and more of ASME's standards activities. This paper will take a look at the direction that ASME nuclear Codes and Standards are heading in this and other areas, as well as taking a look at some advance reactor concepts and plans for standards to address new technologies

Dynamic fracture toughness of ASME SA508 Class 2a ASME SA533 grade A Class 2 base and heat affected zone material and applicable weld metals

International Nuclear Information System (INIS)

Logsdon, W.A.; Begley, J.A.; Gottshall, C.L.

1978-03-01

The ASME Boiler and Pressure Vessel Code, Section III, Article G-2000, requires that dynamic fracture toughness data be developed for materials with specified minimum yield strengths greater than 50 ksi to provide verification and utilization of the ASME specified minimum reference toughness K/sub IR/ curve. In order to qualify ASME SA508 Class 2a and ASME SA533 Grade A Class 2 pressure vessel steels (minimum yield strengths equal 65 kip/in. 2 and 70 kip/in. 2 , respectively) per this requirement, dynamic fracture toughness tests were performed on these materials. All dynamic fracture toughness values of SA508 Class 2a base and HAZ material, SA533 Grade A Class 2 base and HAZ material, and applicable weld metals exceeded the ASME specified minimum reference toughness K/sub IR/ curve

Penetration of ASM 981 in canine skin: a comparative study.

Science.gov (United States)

Gutzwiller, Meret E Ricklin; Reist, Martin; Persohn, Elke; Peel, John E; Roosje, Petra J

2006-01-01

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.

ASME factory authorization system and the situation in Japan

International Nuclear Information System (INIS)

Futagawa, Kiyoshi

1978-01-01

Since about three or four years ago, the enterprises of machinery, iron and steel and welding materials in Japan are paying much attention to the acquisition of ASME (American Society of Mechanical Engineers) certificates or authorization to stamp the code symbols. That is, over 70 factories in Japan have undergone ASME examination, and consequently acquired the authorization or certificates. Such authorization is divided into over 20 kinds, of which about 7 are possessed by the companies in Japan. In nuclear field, the kinds of authorization are N (nuclear vessel), NPT (nuclear vessel parts), NV (nuclear vessel safety valve), and MM (material manufacturing). In non-nuclear fields, they are S (power boilers), U (pressure vessels, in Div. 1), and U2 (pressure vessels in Div. 2). The following matters are described: ASME setup, authorization procedures of ASME for factories, the kinds of authorization, factories in Japan holding the authorization or certificates, and renewal of the authorization. (Mori, K.)

Statistical analysis of the ASME KIc database

International Nuclear Information System (INIS)

Sokolov, M.A.

1998-01-01

The American Society of Mechanical Engineers (ASME) K Ic curve is a function of test temperature (T) normalized to a reference nil-ductility temperature, RT NDT , namely, T-RT NDT . It was constructed as the lower boundary to the available K Ic database. Being a lower bound to the unique but limited database, the ASME K Ic curve concept does not discuss probability matters. However, a continuing evolution of fracture mechanics advances has led to employment of the Weibull distribution function to model the scatter of fracture toughness values in the transition range. The Weibull statistic/master curve approach was applied to analyze the current ASME K Ic database. It is shown that the Weibull distribution function models the scatter in K Ic data from different materials very well, while the temperature dependence is described by the master curve. Probabilistic-based tolerance-bound curves are suggested to describe lower-bound K Ic values

Bronchodilatory and anti-inflammatory effects of ASM-024, a nicotinic receptor ligand, developed for the treatment of asthma.

Science.gov (United States)

Assayag, Evelyne Israël; Beaulieu, Marie-Josée; Cormier, Yvon

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145 ± 0.032 mg/kg for ASM 024-treated group as compared to 0.088 ± 0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD.

MicroRNA-20b-5p inhibits platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3.

Science.gov (United States)

Tang, Jin; Luo, Lingying

2018-06-01

Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF). Here, we showed that miR-20b-5p was significantly decreased in fetal ASM cells treated with PDGF. Biological experiments showed that the overexpression of miR-20b-5p inhibited the proliferation while miR-20b-5p inhibition markedly promoted the proliferation of fetal ASM cells. Bioinformatics analysis and luciferase reporter assay showed that miR-20b-5p directly targeted the 3'-UTR of signal transducer and activator of transcription 3 (STAT3). Further data showed that miR-20b-5p negatively regulated the expression of STAT3 in fetal ASM cells. Moreover, miR-20b-5p regulates the transcriptional activity of STAT3 in fetal ASM cells. Overexpression of STAT3 reversed the inhibitory effect of miR-20b-5p overexpression on fetal ASM cell proliferation while the knockdown of STAT3 abrogated the promoted effect of miR-20b-5p inhibition on fetal ASM cell proliferation. Overall, our results show that miR-20b-5p impedes PDGF-induced proliferation of fetal ASM cells through targeting STAT3. Our study suggests that miR-20b-5p may play an important role in airway remodeling during asthma and suggests that miR-20b-5p may serve as a potential therapeutic target for pediatric asthma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

ASME nuclear codes and standards: Scope of coverage and current initiatives

International Nuclear Information System (INIS)

Eisenberg, G. M.

1995-01-01

The objective of this paper is to address the broad scope of coverage of nuclear codes, standards and guides produced and administered by the American Society of Mechanical Engineers (ASME). Background information is provided regarding the evolution of the present activities. Details are provided on current initiatives intended to permit ASME to meet the needs of a changing nuclear industry on a worldwide scale. During the early years of commercial nuclear power, ASME produced a code for the construction of nuclear vessels used in the reactor coolant pressure boundary, containment and auxiliary systems. In response to industry growth, ASME Code coverage soon broadened to include rules for construction of other nuclear components, and inservice inspection of nuclear reactor coolant systems. In the years following this, the scope of ASME nuclear codes, standards and guides has been broadened significantly to include air cleaning activities for nuclear power reactors, operation and maintenance of nuclear power plants, quality assurance programs, cranes for nuclear facilities, qualification of mechanical equipment, and concrete reactor vessels and containments. ASME focuses on globalization of its codes, standards and guides by encouraging and promoting their use in the international community and by actively seeking participation of international members on its technical and supervisory committees and in accreditation activities. Details are provided on current international representation. Initiatives are underway to separate the technical requirements from administrative and enforcement requirements, to convert to hard metric units, to provide for non-U. S. materials, and to provide for translations into non-English languages. ASME activity as an accredited ISO 9000 registrar for suppliers of mechanical equipment is described. Rules are being developed for construction of containment systems for nuclear spent fuel and high-level waste transport packagings. Intensive

Highlights of proposed changes to ANSI/ASME N509-80

International Nuclear Information System (INIS)

Ornberg, S.C.

1987-01-01

The ASME Committee on Nuclear Air and Gas Treatment (CONAGT) are at the time of this writing considering performing maintenance revisions of ANSI N509 and N510 based on the results of a required 5-year review and comments received from users of the standards at workshops and through inquiries. This paper discusses the highlights of the significant revisions to ANSI/ASME N509 and explains the reasons for the changes. It should be emphasized that these revisions are not yet approved by ASME CONAGT, the board of Nuclear Codes and Standards, or ANSI

CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro.

Science.gov (United States)

Alkhouri, H; Moir, L M; Armour, C L; Hughes, J M

2014-03-01

Activated mast cells (MC) numbers on airway smooth muscle (ASM) are increased in eosinophilic asthma. In vitro, asthmatic cytokine-stimulated ASM cell-conditioned medium (CM) induces more MC chemotaxis than CM from nonasthmatic ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the asthmatic ASM CM. However, the inhibitory factor(s) in the nonasthmatic ASM CM is still to be identified. To identify the factor(s) released by nonasthmatic ASM cells that inhibits MC chemotaxis. Confluent, serum-starved ASM cells from donors with and without asthma were stimulated with IL-1β and T-helper (Th)1 (TNFα and IFNγ) or Th2 (IL-4, IL-13) cytokines, or left unstimulated. CM samples were collected after 24 h, and a potential inhibitory factor identified using cytokine protein arrays. Its production was assessed using ELISA and RT-PCR and inhibitory role investigated in MC chemotaxis and Ca(2+) mobilization assays. Only CXCL1 was produced in greater amounts by nonasthmatic than asthmatic ASM cells following Th1 and Th2 cytokine stimulation. CXCL1 mRNA expression was also increased. Exogenous rh-CXCL1 significantly inhibited MC intracellular Ca(2+) mobilization and chemotaxis to either CXCL10, CXCL8 or CM collected from asthmatic ASM cells following Th1 or Th2 cytokine stimulation. Neutralizing CXCL1 in nonasthmatic ASM CM or blocking its receptor significantly promoted MC chemotaxis. CXCL1 was a major factor regulating MC chemotaxis in vitro. Its differential release by ASM cells may explain the differences observed in MC localization to the ASM of people with and without asthma. CXCL1 inhibition of MC recruitment to the ASM may lead to new targets to limit asthma pathophysiology. © 2013 John Wiley & Sons Ltd.

Equilíbrio corporal em crianças e adolescentes asmáticos e não asmáticos

Directory of Open Access Journals (Sweden)

Marta Cristina Rodrigues da Silva

2013-06-01

Full Text Available O objetivo foi analisar e comparar o equilíbrio corporal em crianças e adolescentes asmáticos e não asmáticos. Fizeram parte do grupo de estudos 24 sujeitos com idades de 7 a 14 anos divididos em dois grupos: grupo asmático e grupo controle. Para avaliação do equilíbrio corporal utilizou-se uma plataforma de força. Foram utilizadas as condições, olhos abertos e fechados com três tentativas aleatórias, com duração de 30 segundos cada uma. Os resultados apontaram diferença significativa entre os grupos, no teste de equilíbrio com olhos abertos apresentando maior amplitude de deslocamento na direção ântero-posterior (COPap (p = 0,04, e médio lateral (COPml (p = 0,02 no grupo asmático. Enquanto que no teste com olhos fechados a diferença foi significante apenas na amplitude de deslocamento ântero-posterior (COPap (p = 0,02 e Área de Elipse (p=0,03. Desse modo, a asma com suas limitações e consequências parece influenciar negativamente no equilíbrio corporal de seus portadores quando comparados com crianças sem a patologia e da mesma faixa etária.

Consideration of the Construction Code for TBM-body in ASME BPVC

International Nuclear Information System (INIS)

Kim, Dongjun; Kim, Yunjae; Kim, Suk Kwon; Park, Sung Dae; Lee, Dong Won

2016-01-01

In this paper, ASME code is briefly introduced, and the TBM-body is classified for selecting the ASME section. With the classification of TBM-body, the appropriate section is determined. Helium Cooled Ceramic Reflector (HCCR) Test Blanket System (TBS) has been designed to research on the functions of breeding blanket by KO TBM team. The functions has three subjects as 1) Tritium breeding, 2) Heat conversion and extraction, and 3) Neutron and Gamma-ray shielding. For the process of design, it is needed to select the appropriate construction code as the design criteria. ITER Organization (IO) has proposed that RCC-MR Edition 2007 ver. shall be used for TBM-shield. Because the TBM-shield is connected to the vacuum boundary. For the other part of TBM-set, TBM-body, there is no constraint on the selected code, and the manufacturer can appropriately select the construction code to apply design and fabrication parts. KO TBM Team has considered whether it is appropriate to choose any code for TBM-body. One of the things is ASME code. The advantage of ASME choice is suitable to the domestic status. In the domestic nuclear plant, ASME or KEPIC code is used as regulatory requirements. Based on this, it is possible to prepare a domestic fusion plant regulatory. In this paper, the construction code of TBM-body was determined in ASME BPVC. For the determination of code, the structure of ASME BPVC was introduced and the classification for TBM-body was conducted by the ITER criteria. And the operation conditions of TBM-body that contained creep and irradiation effects was considered to determine the construction code

Consideration of the Construction Code for TBM-body in ASME BPVC

Energy Technology Data Exchange (ETDEWEB)

Kim, Dongjun; Kim, Yunjae [Korea Univ., Seoul (Korea, Republic of); Kim, Suk Kwon; Park, Sung Dae; Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

In this paper, ASME code is briefly introduced, and the TBM-body is classified for selecting the ASME section. With the classification of TBM-body, the appropriate section is determined. Helium Cooled Ceramic Reflector (HCCR) Test Blanket System (TBS) has been designed to research on the functions of breeding blanket by KO TBM team. The functions has three subjects as 1) Tritium breeding, 2) Heat conversion and extraction, and 3) Neutron and Gamma-ray shielding. For the process of design, it is needed to select the appropriate construction code as the design criteria. ITER Organization (IO) has proposed that RCC-MR Edition 2007 ver. shall be used for TBM-shield. Because the TBM-shield is connected to the vacuum boundary. For the other part of TBM-set, TBM-body, there is no constraint on the selected code, and the manufacturer can appropriately select the construction code to apply design and fabrication parts. KO TBM Team has considered whether it is appropriate to choose any code for TBM-body. One of the things is ASME code. The advantage of ASME choice is suitable to the domestic status. In the domestic nuclear plant, ASME or KEPIC code is used as regulatory requirements. Based on this, it is possible to prepare a domestic fusion plant regulatory. In this paper, the construction code of TBM-body was determined in ASME BPVC. For the determination of code, the structure of ASME BPVC was introduced and the classification for TBM-body was conducted by the ITER criteria. And the operation conditions of TBM-body that contained creep and irradiation effects was considered to determine the construction code.

ASME nuclear codes and standards: Recent technical initiatives

International Nuclear Information System (INIS)

Feigel, R. E.

1995-01-01

Although nuclear power construction is currently in a hiatus in the US, ASME and its volunteer committees remain committed to continual improvements in the technical requirements in its nuclear codes. This paper provides an overview of several significant recent revisions to ASME' s nuclear codes. Additionally, other important initiatives currently being addressed by ASME committees will be described. With the largest population of operating light water nuclear plants in the world and worldwide use of its nuclear codes, ASME continues to support technical advancements in its nuclear codes and standards. While revisions of various magnitude are an ongoing process, several recent revisions embody significant changes based on state of the art design philosophy and substantial industry experience. In the design area, a significant revisions has recently been approved which will significantly reduce conservatisms in seismic piping design as well as provide simplified design rules. Major revisions have also been made to the requirements for nuclear material manufacturers and suppliers, which should result in clearer understanding of this difficult administrative area of the code. In the area of Section XI inservice rules, substantial studies are underway to investigate the application of probabilistic, risked based inspection in lieu of the current deterministic inspection philosophy. While much work still is required in this area, it is an important potential application of the emerging field of risk based inspection

A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

LENUS (Irish Health Repository)

Prendergast, James G D

2012-05-19

AbstractBackgroundChromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).ResultsUsing a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.ConclusionThese results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.

ASME Code Efforts Supporting HTGRs

Energy Technology Data Exchange (ETDEWEB)

D.K. Morton

2012-09-01

In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This report discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.

ASME Code Efforts Supporting HTGRs

Energy Technology Data Exchange (ETDEWEB)

D.K. Morton

2011-09-01

In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This report discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.

Analysis of the Current Technical Issues on ASME Code and Standard for Nuclear Mechanical Design(2009)

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Lee, B. S.; Yoo, S. H.

2009-11-01

This report describes the analysis on the current revision movement related to the mechanical design issues of the U.S ASME nuclear code and standard. ASME nuclear mechanical design in this report is composed of the nuclear material, primary system, secondary system and high temperature reactor. This report includes the countermeasures based on the ASME Code meeting for current issues of each major field. KAMC(ASME Mirror Committee) of this project is willing to reflect a standpoint of the domestic nuclear industry on ASME nuclear mechanical design and play a technical bridge role for the domestic nuclear industry in ASME Codes application

Analysis of the Current Technical Issues on ASME Code and Standard for Nuclear Mechanical Design(2009)

Energy Technology Data Exchange (ETDEWEB)

Koo, Gyeong Hoi; Lee, B. S.; Yoo, S. H.

2009-11-15

This report describes the analysis on the current revision movement related to the mechanical design issues of the U.S ASME nuclear code and standard. ASME nuclear mechanical design in this report is composed of the nuclear material, primary system, secondary system and high temperature reactor. This report includes the countermeasures based on the ASME Code meeting for current issues of each major field. KAMC(ASME Mirror Committee) of this project is willing to reflect a standpoint of the domestic nuclear industry on ASME nuclear mechanical design and play a technical bridge role for the domestic nuclear industry in ASME Codes application

GC-ASM: Synergistic Integration of Graph-Cut and Active Shape Model Strategies for Medical Image Segmentation.

Science.gov (United States)

Chen, Xinjian; Udupa, Jayaram K; Alavi, Abass; Torigian, Drew A

2013-05-01

Image segmentation methods may be classified into two categories: purely image based and model based. Each of these two classes has its own advantages and disadvantages. In this paper, we propose a novel synergistic combination of the image based graph-cut (GC) method with the model based ASM method to arrive at the GC-ASM method for medical image segmentation. A multi-object GC cost function is proposed which effectively integrates the ASM shape information into the GC framework. The proposed method consists of two phases: model building and segmentation. In the model building phase, the ASM model is built and the parameters of the GC are estimated. The segmentation phase consists of two main steps: initialization (recognition) and delineation. For initialization, an automatic method is proposed which estimates the pose (translation, orientation, and scale) of the model, and obtains a rough segmentation result which also provides the shape information for the GC method. For delineation, an iterative GC-ASM algorithm is proposed which performs finer delineation based on the initialization results. The proposed methods are implemented to operate on 2D images and evaluated on clinical chest CT, abdominal CT, and foot MRI data sets. The results show the following: (a) An overall delineation accuracy of TPVF > 96%, FPVF ASM for different objects, modalities, and body regions. (b) GC-ASM improves over ASM in its accuracy and precision to search region. (c) GC-ASM requires far fewer landmarks (about 1/3 of ASM) than ASM. (d) GC-ASM achieves full automation in the segmentation step compared to GC which requires seed specification and improves on the accuracy of GC. (e) One disadvantage of GC-ASM is its increased computational expense owing to the iterative nature of the algorithm.

Operating nuclear plant feedback to ASME and French codes

International Nuclear Information System (INIS)

Journet, J.; O'Donnell, W.J.

1996-01-01

The French have an advantage in nuclear plant operating experience feedback due to the highly centralized nature of their nuclear industry. There is only one utility in charge of design as well as operations (EDF) and only one reactor vendor (Framatome). The ASME Code has played a key role in resolving technical issues in the design and operation of nuclear plants since the inception of nuclear power. The committee structure of the Code brings an ideal combination of senior technical people with both broad and specialized experience to bear on complex how safe is safe enough technical issues. The authors now see an even greater role for the ASME Code in a proposed new regulatory era for the US nuclear industry. The current legalistic confrontational regulatory era has been quite destructive. There now appears to be a real opportunity to begin a new era of technical consensus as the primary means for resolving safety issues. This change can quickly be brought about by having the industry take operating plant problems and regulatory technical issues directly to the ASME Code for timely resolution. Surprisingly, there is no institution in the US nuclear industry with such a mandate. In fact, the industry is organized to feedback through the Nuclear Regulatory Commission issues which could be far better resolved through the ASME Code. Major regulatory benefits can be achieved by closing this loop and providing systematic interaction with the ASME Code. The essential elements of a new regulatory era and ideas for organizing US institutional industry responsibilities, taken from the French experience, are described in this paper

ASME method for particle reconstruction

International Nuclear Information System (INIS)

Ierusalimov, A.P.

2009-01-01

The method of approximate solution of motion equation (ASME) was used to reconstruct the parameters for charged particles. It provides a good precision for momentum, angular and space parameters of particles in coordinate detectors. The application of the method for CBM, HADES and MPD/NICA setups is discussed

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells

NARCIS (Netherlands)

S. McKay (Sue); S.J. Hirst (Stuart); M. Bertrand-de Haas (Marion); J.C. de Jongste (Johan); H.C. Hoogsteden (Henk); P.R. Saxena (Pramod Ranjan); H.S. Sharma (Hari)

2000-01-01

textabstractAirway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We

Regulatory Endorsement Activities for ASME Nuclear Codes and Standards

International Nuclear Information System (INIS)

West, Raymond A.

2006-01-01

The ASME Board on Nuclear Codes and Standards (BNCS) has formed a Task Group on Regulatory Endorsement (TG-RE) that is currently in discussions with the United States Nuclear Regulatory Commission (NRC) to look at suggestions and recommendations that can be used to help with the endorsement of new and revised ASME Nuclear Codes and Standards (NC and S). With the coming of new reactors in the USA in the very near future we need to look at both the regulations and all the ASME NC and S to determine where we need to make changes to support these new plants. At the same time it is important that we maintain our operating plants while addressing ageing management needs of our existing reactors. This is going to take new thinking, time, resources, and money. For all this to take place the regulations and requirements that we use must be clear concise and necessary for safety and to that end both the NRC and ASME are working together to make this happen. Because of the influence that the USA has in the world in dealing with these issues, this paper is written to inform the international nuclear engineering community about the issues and what actions are being addressed under this effort. (author)

Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs.

Science.gov (United States)

Hasaneen, Nadia A; Zucker, Stanley; Cao, Jian; Chiarelli, Christian; Panettieri, Reynold A; Foda, Hussein D

2005-09-01

Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.

Risk-informed technology developments for nuclear power plants within the ASME in 2000-2001

International Nuclear Information System (INIS)

Wesley Rowley, C.; Balkey, K.R.

2001-01-01

The purpose of this paper is to provide information on developments within the ASME to support risk-informing NRC regulations for nuclear power plants. This paper builds on a publication at ICONE-8 that discussed ASME risk-informed nuclear power plant initiatives, both in Research and in Codes and Standards, particularly those related to risk-informing Part 50 of the 10 CFR (Code of federal regulations). During the past year, the ASME BNCS formed a Task Force to focus the Society's efforts to support risk-informing 10 CFR Part 50. Key efforts underway that are guided by the task force include finalizing the ASME PRA (probability risk assessment) Standard, developing a Code Case to risk-inform the repair, replacement, and modification activities for ASME components, and developing a Code Case to risk-inform the safety classification of pressure boundary components. Several other initiatives are also under investigation such as introducing risk insights into other ASME nuclear codes and standards supported by appropriate research and technical basis information. Supplementary information will also be provided to update an initial high level plan of ASME risk-informed initiatives for nuclear power plants that was presented at ICONE-8, including plans to communicate these risk-informed technology developments to the public. The authors included and acknowledged contributions from several other cognizant members of the ASME BNCS (board on nuclear codes standards) Task Group on RIP50 in the paper. (authors)

Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase

DEFF Research Database (Denmark)

Petersen, Nikolaj H T; Olsen, Ole D; Groth-Pedersen, Line

2013-01-01

Lysosomal membrane permeabilization and subsequent cell death may prove useful in cancer treatment, provided that cancer cell lysosomes can be specifically targeted. Here, we identify acid sphingomyelinase (ASM) inhibition as a selective means to destabilize cancer cell lysosomes. Lysosome......-destabilizing experimental anticancer agent siramesine inhibits ASM by interfering with the binding of ASM to its essential lysosomal cofactor, bis(monoacylglycero)phosphate. Like siramesine, several clinically relevant ASM inhibitors trigger cancer-specific lysosomal cell death, reduce tumor growth in vivo, and revert...

Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.

Science.gov (United States)

Watson, Brittany M; Oliveria, John Paul; Nusca, Graeme M; Smith, Steven G; Beaudin, Sue; Dua, Benny; Watson, Rick M; Assayag, Evelynne Israël; Cormier, Yvon F; Sehmi, Roma; Gauvreau, Gail M

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses. © 2015 S. Karger AG, Basel.

Glioma cell death induced by irradiation or alkylating agent chemotherapy is independent of the intrinsic ceramide pathway.

Directory of Open Access Journals (Sweden)

Dorothee Gramatzki

Full Text Available Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells.Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II-IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations.Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation.Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of

Analysis of preservice inspection relief requests and recommendations for ASME code changes

International Nuclear Information System (INIS)

Cook, J.F.

1985-05-01

NRC regulations require that preservice inspection (PSI) of nuclear plants be performed in accordance with referenced editions and addenda of Division 1 rules of Section XI, ''Rules for Inservice Inspection of Nuclear Power Plant Components'', of the ASME Boiler and Pressure Vessel Code (ASME Code). The regulations permit applicants to request and obtain relief from the NRC from specific ASME Code requirements that are determined to be impractical. Applicant requests for relief from preservice inspection (PSI) requirements were compiled and analyzed. From this data, covering a total of 178 relief requests, common problems with examination requirements were identified. Changes to examination requirements to solve selected problems are proposed. By following later ASME Code requirements, 46 out of the 178 relief requests can be eliminated. Implementing proposed Code changes would eliminate another 25 relief requests, leaving 107 relief requests out of the original 178 relief requests covered by this survey

Evaluation of practicality of ASME code, Section XI

International Nuclear Information System (INIS)

Mattu, R.K.; Lauderdale, J.R.; Liu, S.N.; Lance, J.J.

2004-01-01

Many nuclear power plants have found that it is impractical or unduly burdensome to comply with some ASME Boiler and Pressure Code provisions and have sought relief from those provisions from the Nuclear Regulatory Commission. An Electric Power Research Institute (EPRI) project is evaluating such Code provisions and alternatives to them that will meet the safety intent of the Code with less burden on utilities. The methodology is to extract data from an on-line data base of relief requests since 1980, analyse the data to identify burdensome provisions for which there are satisfactory alternatives, and recommend changes in the Code to the ASME. (author)

NIST/ASME Steam Properties Database

Science.gov (United States)

SRD 10 NIST/ASME Steam Properties Database (PC database for purchase)   Based upon the International Association for the Properties of Water and Steam (IAPWS) 1995 formulation for the thermodynamic properties of water and the most recent IAPWS formulations for transport and other properties, this updated version provides water properties over a wide range of conditions according to the accepted international standards.

High Level Analysis, Design and Validation of Distributed Mobile Systems with CoreASM

Science.gov (United States)

Farahbod, R.; Glässer, U.; Jackson, P. J.; Vajihollahi, M.

System design is a creative activity calling for abstract models that facilitate reasoning about the key system attributes (desired requirements and resulting properties) so as to ensure these attributes are properly established prior to actually building a system. We explore here the practical side of using the abstract state machine (ASM) formalism in combination with the CoreASM open source tool environment for high-level design and experimental validation of complex distributed systems. Emphasizing the early phases of the design process, a guiding principle is to support freedom of experimentation by minimizing the need for encoding. CoreASM has been developed and tested building on a broad scope of applications, spanning computational criminology, maritime surveillance and situation analysis. We critically reexamine here the CoreASM project in light of three different application scenarios.

Estimates of margins in ASME Code strength values for stainless steel nuclear piping

International Nuclear Information System (INIS)

Ware, A.G.

1995-01-01

The margins in the ASME Code stainless steel allowable stress values that can be attributed to the variations in material strength are evaluated for nuclear piping steels. Best-fit curves were calculated for the material test data that were used to determine allowable stress values for stainless steels in the ASME Code, supplemented by more recent data, to estimate the mean stresses. The mean yield stresses (on which the stainless steel S m values are based) from the test data are about 15 to 20% greater than the ASME Code yield stress values. The ASME Code yield stress values are estimated to approximately coincide with the 97% confidence limit from the test data. The mean and 97% confidence limit values can be used in the probabilistic risk assessments of nuclear piping

A comparative study for SMART steam generator sizing based on ASME and Russian standard

International Nuclear Information System (INIS)

Kim, Y. W.; Kim, J. I.; Jang, M. H.

2000-01-01

A systematic comparison of ASME and Russian standard with respect to the design of SMART steam generator has been carried out. Classification of allowable stress in the Russian standard is quite different from that of ASME. Allowable stress of Russian standard and stress intensity defined in ASME were compared for various steam generator tube material as a function of design temperature. Equations and methodology of determining the thickness for the important parts of steam generator have been analyzed. For the tube subjected to internal and/or external pressure, Russian standard use the same equation in the sizing of tube with different allowable stress. However, ASME use different equations with the same value of allowable stress intensity. The hydraulic test pressure of ASME was also compared with that of Russian standard. In general, hydraulic test pressure determined by Russian standard is higher since it considers difference between allowable stress of test temperature and that of design temperature

A minimal path searching approach for active shape model (ASM)-based segmentation of the lung

Science.gov (United States)

Guo, Shengwen; Fei, Baowei

2009-02-01

We are developing a minimal path searching method for active shape model (ASM)-based segmentation for detection of lung boundaries on digital radiographs. With the conventional ASM method, the position and shape parameters of the model points are iteratively refined and the target points are updated by the least Mahalanobis distance criterion. We propose an improved searching strategy that extends the searching points in a fan-shape region instead of along the normal direction. A minimal path (MP) deformable model is applied to drive the searching procedure. A statistical shape prior model is incorporated into the segmentation. In order to keep the smoothness of the shape, a smooth constraint is employed to the deformable model. To quantitatively assess the ASM-MP segmentation, we compare the automatic segmentation with manual segmentation for 72 lung digitized radiographs. The distance error between the ASM-MP and manual segmentation is 1.75 +/- 0.33 pixels, while the error is 1.99 +/- 0.45 pixels for the ASM. Our results demonstrate that our ASM-MP method can accurately segment the lung on digital radiographs.

A Minimal Path Searching Approach for Active Shape Model (ASM)-based Segmentation of the Lung.

Science.gov (United States)

Guo, Shengwen; Fei, Baowei

2009-03-27

We are developing a minimal path searching method for active shape model (ASM)-based segmentation for detection of lung boundaries on digital radiographs. With the conventional ASM method, the position and shape parameters of the model points are iteratively refined and the target points are updated by the least Mahalanobis distance criterion. We propose an improved searching strategy that extends the searching points in a fan-shape region instead of along the normal direction. A minimal path (MP) deformable model is applied to drive the searching procedure. A statistical shape prior model is incorporated into the segmentation. In order to keep the smoothness of the shape, a smooth constraint is employed to the deformable model. To quantitatively assess the ASM-MP segmentation, we compare the automatic segmentation with manual segmentation for 72 lung digitized radiographs. The distance error between the ASM-MP and manual segmentation is 1.75 ± 0.33 pixels, while the error is 1.99 ± 0.45 pixels for the ASM. Our results demonstrate that our ASM-MP method can accurately segment the lung on digital radiographs.

Passport of global nuclear business. ASME code certificate acquirement and inspection practices

International Nuclear Information System (INIS)

Kawabata, Hiroyuki; Terajima, Makoto; Anami, Kazuhiro

2010-01-01

There are possibilities of Japanese nuclear industries to participate in global business such as new and additional construction of nuclear power plants in US and also Asian and other developing countries in the world. It is requisite to acquire ASME code certificate for global business participation, just as passport. This article consists of five papers on present status of ASME code certificate acquirement and inspection practices of nuclear components vendors in the area of Japanese nuclear business. Activities of JSME Committee on Power Generation Facility Codes to make JSME codes corresponded to ASME nuclear codes and standards for their international deployment are also described. (T. Tanaka)

Review of ASME nuclear codes and standards- subcommittee on repairs, replacements, and modifications

International Nuclear Information System (INIS)

Mawson, T.J.

1990-01-01

As requested by the ASME board on Nuclear Codes and Standards, the Pressure Vessel Research Committee initiated a project to review Sections III and XI of the ASME Boiler and Pressure Vessel Code for the purposes of improving, clarifying, providing transition, consistency, compatibility, and simplifying code requirements. The project was organized with six subcommittees to address various Code activities: design; tests and examinations; documentation; quality assurance; repair, replacement and modification; and general requirements. This paper discusses how the subcommittee on repair, replacement and modification was organized to review the repair, replacement and modification requirements of the ASME boiler and pressure vessel code, Section III and Section XI for Class 1, 2, and 3 and MC components and their supports, and other documents of the nuclear industry related to the repair, replacement and modification requirements of the ASME code

[Ca2+]i oscillations in ASM: relationship with persistent airflow obstruction in asthma.

Science.gov (United States)

Sweeney, David; Hollins, Fay; Gomez, Edith; Saunders, Ruth; Challiss, R A John; Brightling, Christopher E

2014-07-01

The cause of airway smooth muscle (ASM) hypercontractility in asthma is not fully understood. The relationship of spontaneous intracellular calcium oscillation frequency in ASM to asthma severity was investigated. Oscillations were increased in subjects with impaired lung function abolished by extracellular calcium removal, attenuated by caffeine and unaffected by verapamil or nitrendipine. Whether modulation of increased spontaneous intracellular calcium oscillations in ASM from patients with impaired lung function represents a therapeutic target warrants further investigation. © 2014 The Authors. Respirology published by Wiley Publishing Asia Pty Ltd on behalf of Asian Pacific Society of Respirology.

Investigating ASME allowable loads with finite element analyses

International Nuclear Information System (INIS)

Mattar Neto, Miguel; Bezerra, Luciano M.; Miranda, Carlos A. de J.; Cruz, Julio R.B.

1995-01-01

The evaluation of nuclear components using finite element analysis (FEA) does not generally fall into the shell type verification adopted by the ASME Code. Consequently, the demonstration that the modes of failure are avoided sometimes is not straightforward. Allowable limits, developed by limit load theory, require the computation of shell membrane and bending stresses. How to calculate these stresses from FEA is not necessarily self-evident. One approach to be considered is to develop recommendations in a case-by-case basis for the most common pressure vessel geometries and loads based on comparison between the results of elastic and plastic FEA. In this paper, FE analyses of common 2D and complex 3D geometries are examined and discussed. It will be clear that in the cases studied, stress separation and categorization are not self-evident and simple tasks to undertake. Certain unclear recommendations of ASME Code can lead the stress analyst to non conservative designs as will be demonstrated in this paper. At the endo of this paper, taking into account comparison between elastic and elastic-plastic FE results from ANSYS some observations, suggestions and conclusions about the degree of conservatism of the ASME recommendations will be addressed. (author)

ASM LabCap's contributions to disease surveillance and the International Health Regulations (2005).

Science.gov (United States)

Specter, Steven; Schuermann, Lily; Hakiruwizera, Celestin; Sow, Mah-Séré Keita

2010-12-03

The revised International Health Regulations [IHR(2005)], which requires the Member States of the World Health Organization (WHO) to develop core capacities to detect, assess, report, and respond to public health threats, is bringing new challenges for national and international surveillance systems. As more countries move toward implementation and/or strengthening of their infectious disease surveillance programs, the strengthening of clinical microbiology laboratories becomes increasingly important because they serve as the first line responders to detect new and emerging microbial threats, re-emerging infectious diseases, the spread of antibiotic resistance, and the possibility of bioterrorism. In fact, IHR(2005) Core Capacity #8, "Laboratory", requires that laboratory services be a part of every phase of alert and response.Public health laboratories in many resource-constrained countries require financial and technical assistance to build their capacity. In recognition of this, in 2006, the American Society for Microbiology (ASM) established an International Laboratory Capacity Building Program, LabCap, housed under the ASM International Board. ASM LabCap utilizes ASM's vast resources and its membership's expertise-40,000 microbiologists worldwide-to strengthen clinical and public health laboratory systems in low and low-middle income countries. ASM LabCap's program activities align with HR(2005) by building the capability of resource-constrained countries to develop quality-assured, laboratory-based information which is critical to disease surveillance and the rapid detection of disease outbreaks, whether they stem from natural, deliberate or accidental causes.ASM LabCap helps build laboratory capacity under a cooperative agreement with the U.S. Centers for Disease Control and Prevention (CDC) and under a sub-contract with the Program for Appropriate Technology in Health (PATH) funded by the United States Agency for International Development (USAID

ASME section XI: rules for inservice inspection of nuclear power plants -an introspection

Energy Technology Data Exchange (ETDEWEB)

John, P K; Anto, Y; Mungikar, C P; Wagh, P M [Nuclear Power Corporation of India Ltd., Tarapur (India). Tarapur Atomic Power Station

1994-12-31

Section XI of the ASME BPV code is addressed to the examination, test and inspection requirements of the components of nuclear power plants (NPPs). Since its inception in 1970, this code section has undergone vast changes -probably the most among other ASME BPV code sections. Section XI is full fledged and lays down requirements with regard to all preservice inspections, inservice inspection, repair and replacement of components, tests of system etc. Tarapur Atomic Power Station (TAPS) has the distinction of being one of the earliest BWR type NPPs in the world that has an inservice inspection programme organised in line with the ASME section XI requirements. This paper summarises the experiences gained from time to time using this code section and a few suggestions to prospective users. An effort is also made to explain the philosophy of inservice inspection from ASME section XI point of view. 3 refs.

ASME section XI: rules for inservice inspection of nuclear power plants -an introspection

International Nuclear Information System (INIS)

John, P.K.; Anto, Y.; Mungikar, C.P.; Wagh, P.M.

1994-01-01

Section XI of the ASME BPV code is addressed to the examination, test and inspection requirements of the components of nuclear power plants (NPPs). Since its inception in 1970, this code section has undergone vast changes -probably the most among other ASME BPV code sections. Section XI is full fledged and lays down requirements with regard to all preservice inspections, inservice inspection, repair and replacement of components, tests of system etc. Tarapur Atomic Power Station (TAPS) has the distinction of being one of the earliest BWR type NPPs in the world that has an inservice inspection programme organised in line with the ASME section XI requirements. This paper summarises the experiences gained from time to time using this code section and a few suggestions to prospective users. An effort is also made to explain the philosophy of inservice inspection from ASME section XI point of view. 3 refs

Technical requirements for the ASME PRA standard for nuclear power plant applications

International Nuclear Information System (INIS)

Fleming, Karl N.; Bernsen, Sidney A.; Simard, Ronald L.

2000-01-01

In 1998 the American Society of Mechanical Engineers (ASME) formed the Committee on Nuclear Risk Management (CNRM) and a Project Team to develop a standard on PRAs for use in risk informed applications. This ASME standard is being developed to help provide an adequate level of quality in PRAs that are being used to support ASME initiatives to risk informed in-service inspection (ISI) and in-service testing (IST) of nuclear power plant components. A related need supported by the industry and the U.S. Nuclear Regulatory Commission is to reduce the level of effort that is being expended in pilot applications of risk informed initiatives to address questions about the sufficiency of quality in the supporting PRA models. The purpose of this paper is to discuss the authors' views on some of the technical issues that were encountered in the effort to develop the ASME PRA standard. Draft 12 of this standard has been issued for comment, and is currently being finalized with the aim of releasing the standard in early 2001. (author)

Interpreting ASME limits and philosophy in FEA of pressure vessel parts

International Nuclear Information System (INIS)

Bezerra, L.M.; Cruz, J.R.B.; Miranda, C.A.J.; Neto, M.M.

1995-01-01

In recent years there has been an effort to interpret finite element (FE) stress results on the light of the ASME B and PV rules and philosophy. Many task groups have issued guidelines on stress linearization and classifications. All those attempts have come up trying to cope modern FE techniques with the rules imposed by the ASME Code. This paper is an independent contribution to the Pressure Vessel Research Council (PVRC) groups which are studying the stress classification and the failure mechanism in a FE framework. This work tries to complement the interesting work by Hollinger and Hechmer presented in the PVP-94 in Minneapolis. In that paper, the authors examined a typical support skirt and showed relations between the skirt collapse load obtained by finite element analysis and the loads allowed from the ASME stress limits. To complement such paper, in the present article, different skirt geometry configurations are analyzed. The configurations here investigated consist of similar support skirts but with different angles of attachments between cylinder and cone parts. It will be possible to observe the influence of the bending stress in the collapse load and its relation to the allowable loads inferred from the ASME limits. A pressure vessel with torispherical head under internal pressure is also examined. Using elastic and limit load FEA, the present paper determines the collapse loads of the configurations. It sets up the relations between these collapse loads, stress categories, and limits dictated by the ASME Code Subsection NB. On the light of NB rules and philosophy, this paper shows how different methods of stress assessment, classification, and limits may influence in the design of a pressure vessel

14 CFR 330.31 - What data must air carriers submit concerning ASMs or RTMs?

Science.gov (United States)

2010-01-01

... combination passenger/cargo carrier, you must have submitted your August 2001 total completed ASM report to... correct an error that you document to the Department, you must not alter the ASM or RTM reports you...

Design Procedure of Graphite Components by ASME HTR Codes

Energy Technology Data Exchange (ETDEWEB)

Kang, Ji-Ho; Jo, Chang Keun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

In this study, the ASME B and PV Code, Subsection HH, Subpart A, design procedure for graphite components of HTRs was reviewed and the differences from metal materials were remarked. The Korean VHTR has a prismatic core which is made of multiple graphite blocks, reflectors, and core supports. One of the design issues is the assessment of the structural integrity of the graphite components because the graphite is brittle and shows quite different behaviors from metals in high temperature environment. The American Society of Mechanical Engineers (ASME) issued the latest edition of the code for the high temperature reactors (HTR) in 2015. In this study, the ASME B and PV Code, Subsection HH, Subpart A, Graphite Materials was reviewed and the special features were remarked. Due the brittleness of graphites, the damage-tolerant design procedures different from the conventional metals were adopted based on semi-probabilistic approaches. The unique additional classification, SRC, is allotted to the graphite components and the full 3-D FEM or equivalent stress analysis method is required. In specific conditions, the oxidation and viscoelasticity analysis of material are required. The fatigue damage rule has not been established yet.

Design Procedure of Graphite Components by ASME HTR Codes

International Nuclear Information System (INIS)

Kang, Ji-Ho; Jo, Chang Keun

2016-01-01

In this study, the ASME B and PV Code, Subsection HH, Subpart A, design procedure for graphite components of HTRs was reviewed and the differences from metal materials were remarked. The Korean VHTR has a prismatic core which is made of multiple graphite blocks, reflectors, and core supports. One of the design issues is the assessment of the structural integrity of the graphite components because the graphite is brittle and shows quite different behaviors from metals in high temperature environment. The American Society of Mechanical Engineers (ASME) issued the latest edition of the code for the high temperature reactors (HTR) in 2015. In this study, the ASME B and PV Code, Subsection HH, Subpart A, Graphite Materials was reviewed and the special features were remarked. Due the brittleness of graphites, the damage-tolerant design procedures different from the conventional metals were adopted based on semi-probabilistic approaches. The unique additional classification, SRC, is allotted to the graphite components and the full 3-D FEM or equivalent stress analysis method is required. In specific conditions, the oxidation and viscoelasticity analysis of material are required. The fatigue damage rule has not been established yet

The ASM Curriculum Guidelines for Undergraduate Microbiology: A Case Study of the Advocacy Role of Societies in Reform Efforts.

Science.gov (United States)

Horak, Rachel E A; Merkel, Susan; Chang, Amy

2015-05-01

A number of national reports, including Vision and Change in Undergraduate Biology Education: A Call to Action, have called for drastic changes in how undergraduate biology is taught. To that end, the American Society for Microbiology (ASM) has developed new Curriculum Guidelines for undergraduate microbiology that outline a comprehensive curriculum for any undergraduate introductory microbiology course or program of study. Designed to foster enduring understanding of core microbiology concepts, the Guidelines work synergistically with backwards course design to focus teaching on student-centered goals and priorities. In order to qualitatively assess how the ASM Curriculum Guidelines are used by educators and learn more about the needs of microbiology educators, the ASM Education Board distributed two surveys to the ASM education community. In this report, we discuss the results of these surveys (353 responses). We found that the ASM Curriculum Guidelines are being implemented in many different types of courses at all undergraduate levels. Educators indicated that the ASM Curriculum Guidelines were very helpful when planning courses and assessments. We discuss some specific ways in which the ASM Curriculum Guidelines have been used in undergraduate classrooms. The survey identified some barriers that microbiology educators faced when trying to adopt the ASM Curriculum Guidelines, including lack of time, lack of financial resources, and lack of supporting resources. Given the self-reported challenges to implementing the ASM Curriculum Guidelines in undergraduate classrooms, we identify here some activities related to the ASM Curriculum Guidelines that the ASM Education Board has initiated to assist educators in the implementation process.

The ASM Curriculum Guidelines for Undergraduate Microbiology: A Case Study of the Advocacy Role of Societies in Reform Efforts

Directory of Open Access Journals (Sweden)

Rachel E.A. Horak

2015-03-01

Full Text Available A number of national reports, including Vision and Change in Undergraduate Biology Education: A Call to Action, have called for drastic changes in how undergraduate biology is taught. To that end, the American Society for Microbiology (ASM developed new Curriculum Guidelines for undergraduate microbiology that outline a comprehensive curriculum for any undergraduate introductory microbiology course or program of study. Designed to foster enduring understanding of core microbiology concepts, the Guidelines work synergistically with backwards course design to focus teaching on student-centered goals and priorities.  In order to qualitatively assess how the ASM Curriculum Guidelines are used by educators and learn more about the needs of microbiology educators, the ASM Education Board distributed two surveys to the ASM education community. In this report, we discuss results of these surveys (353 responses. We found that the ASM Curriculum Guidelines are being implemented in many different types of courses at all undergraduate levels. Educators indicated that the ASM Curriculum Guidelines were very helpful when planning courses and assessments. We discuss some specific ways in which the ASM Curriculum Guidelines have been used in undergraduate classrooms. The survey identified some barriers that microbiology educators faced when trying to adopt the ASM Curriculum Guidelines, including lack of time, lack of financial resources, and lack of supporting resources. Given the self-reported challenges to implementing the ASM Curriculum Guidelines in undergraduate classrooms, we identify here some activities related to the ASM Curriculum Guidelines that the ASM Education Board has initiated to assist educators in the implementation process.

ASME Section XI philosophy related to operating nuclear plant fatigue damage protection

International Nuclear Information System (INIS)

Gosselin, S.R.

1995-01-01

When faced with operating fatigue concerns, nuclear plants traditionally look to the requirements contained in the original construction design code, ASME Section 3, as a basis for component operability. These rules constitute the requirements for nuclear power plant vessel and component construction and, when combined with the Owner's Design Specification, provide reasonable assurance of reliable operation. However, once construction is complete and operation begins, the purpose of any subsequent evaluations shifts from component ''design qualification'' to component ''fitness for service.'' This is a role that has been assumed for ASME Section 11. This paper presents a philosophy, recently endorsed by the ASME Section 11 Executive Committee, intended to guide future Code activities regarding fatigue and its impact on component serviceability

115-year-old society knows how to reach young scientists: ASM Young Ambassador Program.

Science.gov (United States)

Karczewska-Golec, Joanna

2015-12-25

With around 40,000 members in more than 150 countries, American Society for Microbiology (ASM) faces the challenge of meeting very diverse needs of its increasingly international members base. The newly launched ASM Young Ambassador Program seeks to aid the Society in this effort. Equipped with ASM conceptual support and financing, Young Ambassadors (YAs) design and pursue country-tailored approaches to strengthen the Society's ties with local microbiological communities. In a trans-national setting, the active presence of YAs at important scientific events, such as 16th European Congress on Biotechnology, forges new interactions between ASM and sister societies. The paper presents an overview of the Young Ambassadors-driven initiatives at both global and country levels, and explores the topic of how early-career scientists can contribute to science diplomacy and international relations. Copyright © 2014 Elsevier B.V. All rights reserved.

Researching on knowledge architecture of design by analysis based on ASME code

International Nuclear Information System (INIS)

Bao Shiyi; Zhou Yu; He Shuyan

2003-01-01

The quality of knowledge-based system's knowledge architecture is one of decisive factors of knowledge-based system's validity and rationality. For designing the ASME code knowledge based system, this paper presents a knowledge acquisition method which is extracting knowledge through document analysis consulted domain experts' knowledge. Then the paper describes knowledge architecture of design by analysis based on the related rules in ASME code. The knowledge of the knowledge architecture is divided into two categories: one is empirical knowledge, and another is ASME code knowledge. Applied as the basement of the knowledge architecture, a general procedural process of design by analysis that is met the engineering design requirements and designers' conventional mode is generalized and explained detailed in the paper. For the sake of improving inference efficiency and concurrent computation of KBS, a kind of knowledge Petri net (KPN) model is proposed and adopted in expressing the knowledge architecture. Furthermore, for validating and verifying of the empirical rules, five knowledge validation and verification theorems are given in the paper. Moreover the research production is applicable to design the knowledge architecture of ASME codes or other engineering standards. (author)

Approaching application of risk-based inspection to ASME code section XI

International Nuclear Information System (INIS)

Hedden, Owen F.

1995-01-01

This paper will describe current efforts within the ASME Boiler and Pressure Vessel Committee's Subcommittee on Nuclear Inservice Inspection to introduce risk-based technology to optimize inservice inspection of nuclear power plants. The subcommittee is responsible for the content of ASME Boiler and Pressure Vessel Code Section XI, Rules for Inservice Inspection of Nuclear Power Plant Components. The paper will first provide the historical background for the inspection program currently in Section XI. It will then describe the development of new technology through the ASME Center for Research and Technology Development program. Next, the work now going on in two of the groups under the Section XI committee will be described in detail. Each of these two efforts is directed toward the application of new risk-based inspection technology to nuclear piping systems. Finally, the directions of additional research and applications of the technology will be discussed. (author)

The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide.

Science.gov (United States)

Perry, Mark M; Tildy, Bernadett; Papi, Alberto; Casolari, Paolo; Caramori, Gaetano; Rempel, Karen Limbert; Halayko, Andrew J; Adcock, Ian; Chung, Kian Fan

2018-05-09

COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H 2 S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. We examined the effect of H 2 S upon ASM cells from COPD patients. ASM cells were isolated from non-smokers, smokers and patients with COPD (n = 9). Proliferation and cytokine release (IL-6 and CXCL8) of ASM was induced by FCS, and measured by bromodeoxyuridine incorporation and ELISA, respectively. Exposure of ASM to H 2 S donors inhibited FCS-induced proliferation and cytokine release, but was less effective upon COPD ASM cells compared to the non-smokers and smokers. The mRNA and protein expression of the enzymes responsible for endogenous H 2 S production (cystathionine-β-synthase [CBS] and 3-mercaptopyruvate sulphur transferase [MPST]) were inhibited by H 2 S donors. Finally, we report that exogenous H 2 S inhibited FCS-stimulated phosphorylation of ERK-1/2 and p38 mitogen activated protein kinases (MAPKs), in the non-smoker and smoker ASM cells, with little effect in COPD cells. H 2 S production provides a novel mechanism for the repression of ASM proliferation and cytokine release. The ability of COPD ASM cells to respond to H 2 S is attenuated in COPD ASM cells despite the presence of the enzymes responsible for H 2 S production.

The approach to analysis of significance of flaws in ASME section III and section XI

International Nuclear Information System (INIS)

Cowan, A.

1979-01-01

ASME III Appendix G and ASME XI Appendix A describe linear elastic fracture mechanics methods to assess the significance of defects in thick-walled pressure vessels for nuclear reactor systems. The assessment of fracture toughness, Ksub(Ic), is based upon recommendations made by a Task Group of the USA Pressure Vessel Research Committee and is dependent upon correlations with drop weight and Charpy V-notch data to give a lower bound of fracture toughness Ksub(IR). The methods used in the ASME Appendices are outlined noting that, whereas ASME III Appendix G defines a procedure for obtaining allowable pressure vessel loadings for normal service in the presence of a defect, ASME XI Appendix A defines methods for assessing the significance of defects (found by volumetric inspection) under normal and emergency and faulted conditions. The methods of analysis are discussed with respect to material properties, flaw characterisation, stress analysis and recommended safety factors; a short discussion is given on the applicability of the data and methods to other materials and non-nuclear structures. (author)

Comparison of SKIFS 2004:1 and Tillsynshandbok PSA against the ASME PRA Standard and European requirements on PSA

International Nuclear Information System (INIS)

Hellstroem, Per

2005-04-01

Requirements on PSA for risk informed applications are expressed in different international documents. The ASME PRA standard published in spring 2002 is one such document, PSA requirements are also expressed in the European Utility Requirements (EUR) for new reactors. The Swedish PSA requirements are provided in the Swedish regulators (SKI) statutes SKIFS 2004:1. SKI also has a review handbook for PSA activities (SKI report 2003:48). The review handbook is a support during review of the utilities PSA activities and the PSAs themselves. The review handbook expresses SKIs expectations by providing so called important aspects for both the PSA work and the PSAs, A comparison of SKIFS requirements and the important aspects in the Review handbook, on one side, and the requirements on PSA in EUR and ASME on the other side, is presented. The comparison shows a large difference in the level of detail in the different documents, where ASME is most detailed and specific. This is expected since the SKI review handbook not is a 'PSA guide' in the same way as the ASME PRA standard. A direct comparison of the ASME PRA standard requirements with the important aspects in the review handbook cannot answer the question which ASME capacity level that is achieved by a PSA meeting all important aspects. The conclusion is that it is not likely to achieve capacity level 2 and 3, since very few ASME level 3 attributes are explicitly expressed as important aspects, though many are expressed in general terms. The review handbook important aspects that are most similar to the ASME capacity level 1 attributes are initiating events, sequence analysis, and system analysis while less similarity is found for analysis of operator actions data analysis, quantification and containment analysis (level 2). Less similarity is found for capacity level 2 and 3. However, the number of additional ASME attributes on capacity level 2 and 3 are few. There are also important aspects in the review handbook that

Inservice inspection procedures and training according to the ASME code

International Nuclear Information System (INIS)

Greenwald, S.M.; Chockie, L.J.

1987-01-01

Mandatory training of the technical staff at a nuclear power plant is of paramount importance if we are to avoid costly plant shutdowns. This training should include the requirements for both Preservice and Inservice Inspection, in addition to Quality Assurance procedures as required by the American Society of Mechanical Engineers (ASME) Code. The training is best accomplished by utilizing instructors who are thoroughly familiar with plant operations and the ASME Code, as well as serving on one of the Code committees. This paper focuses on the Inservice Inspection procedures and the results of an intensive training effort to implement such procedures. (author)

The ASME research task force on risk-based in-service inspection

International Nuclear Information System (INIS)

Balkey, K.R.; Chapman, O.J.V.

1997-01-01

The use of risk-based methods in the development of in-service inspection (ISI) and in-service testing (IST) programs for nuclear power plant and other industrial applications has been studied for the last several years through the American Society of Mechanical Engineers Centre for Research and Technology Development (ASME 1991, 1992, 1994, 1996). The results of this work are being used as a foundation to develop specific requirements for implementation of risk-based technology in ASME Codes and Standards, regulatory requirements and industry programs both in the U.S. and other countries. This paper provides a brief overview of the ASME Research Methodology and how it has been adapted for application to the inspection of piping within the USA. It also relates how the reliability of nondestructive examination (NDE) methods for pressure boundary components can impact the risk and discusses the relationship between this and NDE qualification/demonstration now being implemented in Europe and the USA. (orig.)

Proceedings: 2001 ASME/EPRI Radwaste Workshop

International Nuclear Information System (INIS)

2001-01-01

Nuclear utilities continually evaluate methods to improve operations and reduce costs associated with radioactive waste management. The continuing deregulation process has increased the emphasis on this activity. The Annual ASME/EPRI Workshop facilitates this effort by communicating technology and management improvements throughout the industry. This workshop, restricted to utility radwaste professionals, also serves to communicate practical in-plant improvements with the opportunity to discuss them in detail

Revision of the ASME nuclear quality assurance standard and its historical background

International Nuclear Information System (INIS)

Suzuki, Tetsuya

2009-01-01

ASME NQA-1-2008 'Quality Assurance Requirements for Nuclear Facility Applications' will be endorsed by US NRC by the end of 2009. This standard will apply to design, construction and operation of nuclear power plants newly erected in USA. It is important to Japanese vendors developing nuclear business in USA. Historical background, significance of revision and main revised points of the ASME nuclear quality assurance standard are described in the present paper. (T. Tanaka)

Proceedings: 2000 ASME/EPRI Radwaste Workshop

International Nuclear Information System (INIS)

2001-01-01

Nuclear utilities are continually evaluating methods to improve operations and reduce costs associated with radioactive waste management. The continuing deregulation process has added increased emphasis to this activity. The Annual ASME/EPRI Workshop facilitates this effort by communicating technological and managerial improvements throughout the industry. This workshop, restricted to utility radwaste professionals, also serves to communicate practical in-plant improvements with the opportunity to discuss them in detail

Activation of human acid sphingomyelinase through modification or deletion of C-terminal cysteine.

Science.gov (United States)

Qiu, Huawei; Edmunds, Tim; Baker-Malcolm, Jennifer; Karey, Kenneth P; Estes, Scott; Schwarz, Cordula; Hughes, Heather; Van Patten, Scott M

2003-08-29

One form of Niemann-Pick disease is caused by a deficiency in the enzymatic activity of acid sphingomyelinase. During efforts to develop an enzyme replacement therapy based on a recombinant form of human acid sphingomyelinase (rhASM), purified preparations of the recombinant enzyme were found to have substantially increased specific activity if cell harvest media were stored for several weeks at -20 degrees C prior to purification. This increase in activity was found to correlate with the loss of the single free thiol on rhASM, suggesting the involvement of a cysteine residue. It was demonstrated that a variety of chemical modifications of the free cysteine on rhASM all result in substantial activation of the enzyme, and the modified cysteine responsible for this activation was shown to be the C-terminal residue (Cys629). Activation was also achieved by copper-promoted dimerization of rhASM (via cysteine) and by C-terminal truncation using carboxypeptidase Y. The role of the C-terminal cysteine in activation was confirmed by creating mutant forms of rhASM in which this residue was either deleted or replaced by a serine, with both forms having substantially higher specific activity than wild-type rhASM. These results indicate that purified rhASM can be activated in vitro by loss of the free thiol on the C-terminal cysteine via chemical modification, dimerization, or deletion of this amino acid residue. This method of activation is similar to the cysteine switch mechanism described previously for matrix metalloproteinases and could represent a means of posttranslational regulation of ASM activity in vivo.

Rethinking ASME III seismic analysis for piping operability evaluations

International Nuclear Information System (INIS)

Adams, T.M.; Stevenson, J.D.

1994-01-01

It has been recognized since the mid 1980's that there are very large seismic margins to failure for nuclear piping systems when designed using current industry practice, design criteria, and methods. As a result of this realization there are or have been approximately eighteen initiatives within the ASME , Boiler and Pressure Vessel Code Section III, Division 1, in the form of proposed code cases and proposed code text changes designed to reduce these failure margins to more realistic values. For the most part these initiatives have concentrated on reclassifying seismic inertia stresses in the piping as secondary and increasing the allowable stress limits permitted by Section III of the ASME, Boiler Code. This paper focuses on the application of non-linear spectral analysis methods as a method to reduce the input seismic demand determination and thereby reduce the seismic failure margins. The approach is evaluated using the ASME Boiler Pressure Vessel Code Section III Subgroup on Design benchmark procedure as proposed by the Subgroup's Special Task Group on Integrated Piping Criteria. Using this procedure, criteria are compared to current code criterion and analysis methods, and several other of the currently proposed Boiler and Pressure Vessel, Section III, changes. Finally, the applicability of the non-linear spectral analysis to continued Safe Operation Evaluations is reviewed and discussed

Cell stiffness, contractile stress and the role of extracellular matrix

International Nuclear Information System (INIS)

An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

2009-01-01

Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

Cell stiffness, contractile stress and the role of extracellular matrix

Energy Technology Data Exchange (ETDEWEB)

An, Steven S., E-mail: san@jhsph.edu [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Kim, Jina [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Ahn, Kwangmi [Division of Biostatistics, Penn State College of Medicine, Hershey, PA 17033 (United States); Trepat, Xavier [CIBER, Enfermedades Respiratorias, 07110 Bunyola (Spain); Drake, Kenneth J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Fredberg, Jeffrey J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States)

2009-05-15

Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

Roles of the Outer Membrane Protein AsmA of Salmonella enterica in the Control of marRAB Expression and Invasion of Epithelial Cells▿

OpenAIRE

Prieto, Ana I.; Hernández, Sara B.; Cota, Ignacio; Pucciarelli, M. Graciela; Orlov, Yuri; Ramos-Morales, Francisco; García-del Portillo, Francisco; Casadesús, Josep

2009-01-01

A genetic screen for suppressors of bile sensitivity in DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium yielded insertions in an uncharacterized locus homologous to the Escherichia coli asmA gene. Disruption of asmA suppressed bile sensitivity also in phoP and wec mutants of S. enterica and increased the MIC of sodium deoxycholate for the parental strain ATCC 14028. Increased levels of marA mRNA were found in asmA, asmA dam, asmA phoP, and asmA wec strains of S....

Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase.

Science.gov (United States)

Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

2016-04-15

Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. Copyright © 2016 the American Physiological Society.

Technical justification for ASME code section xi crack detection by visual examination

International Nuclear Information System (INIS)

Nickell, R.E.; Rashid, Y.R.

2001-01-01

A critical technical element of nuclear power plant license renewal in the United States is the demonstration that the effects of aging do not compromise the intended safety function(s) of a system, structure, or component during the extended term of operation. The demonstration may take either of two forms. First, it can be shown that the design basis for the system, structure, or component is sufficiently robust that the aging effects have been insignificant through the current license term, and will continue to be insignificant through the extended term. Alternatively, it can be shown that, while the aging effects may be potentially significant, those effects can be managed and functionality maintained by defined programmatic activities during the extended term of operation. The first of the two approaches is generally provided by the construction basis, such as construction in accordance with the ASME Code Section III and other consensus codes and standards. The second of the two approaches is often provided by periodic inservice inspection and testing, in accordance with the ASME Code Section XI. The purpose of the ASME Section XI inspections and tests is to assure that systems, components, and structures are fit for continued service until the next scheduled inspection or test. The purpose of this paper is to document the effectiveness of the current ASME Code Section XI visual examination procedures in detecting the effects of aging for systems, structures, and components that are tolerant of mature cracks. (author)

ASME and RCC-MR comparison for the prevention of fatigue analysis

International Nuclear Information System (INIS)

Autrusson, B.; Acker, D.

1989-01-01

The purpose of this survey is to compare the simplified methods, without reference to the safety factor allowed for the mechanical properties. An application of both codes, RCC-MR and ASME, on the design of the wall mock-up of the NET project is made and also an estimation with an elastoplastic analysis. In the case of fatigue analysis according to ASME in the plastic field, the elastic stress is magnified by a K e factor derived from stress variation, S n , disregarding geometrical discontinuities. According to RCC-MR, the elastic maximum strain will magnified by two coefficients accounting for plasticity and variation of Poisson ratio

Simulation and optimization of a coking wastewater biological treatment process by activated sludge models (ASM).

Science.gov (United States)

Wu, Xiaohui; Yang, Yang; Wu, Gaoming; Mao, Juan; Zhou, Tao

2016-01-01

Applications of activated sludge models (ASM) in simulating industrial biological wastewater treatment plants (WWTPs) are still difficult due to refractory and complex components in influents as well as diversity in activated sludges. In this study, an ASM3 modeling study was conducted to simulate and optimize a practical coking wastewater treatment plant (CWTP). First, respirometric characterizations of the coking wastewater and CWTP biomasses were conducted to determine the specific kinetic and stoichiometric model parameters for the consecutive aeration-anoxic-aeration (O-A/O) biological process. All ASM3 parameters have been further estimated and calibrated, through cross validation by the model dynamic simulation procedure. Consequently, an ASM3 model was successfully established to accurately simulate the CWTP performances in removing COD and NH4-N. An optimized CWTP operation condition could be proposed reducing the operation cost from 6.2 to 5.5 €/m(3) wastewater. This study is expected to provide a useful reference for mathematic simulations of practical industrial WWTPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Basic requirements of mechanical properties for nuclear pressure vessel materials in ASME-BPV code

International Nuclear Information System (INIS)

Ning Dong; Yao Weida

2011-01-01

The four basic aspects of strengths, ductility, toughness and fatigue strengths can be summarized for overall mechanical properties requirements of materials for nuclear pressure-retaining vessels in ASME-BPV code. These mechanical property indexes involve in the factors of melting, manufacture, delivery conditions, check or recheck for mechanical properties and chemical compositions, etc. and relate to degradation and damage accumulation during the use of materials. This paper specifically accounts for the basic requirements and theoretic basis of mechanical properties for nuclear pressure vessel materials in ASME-BPV code and states the internal mutual relationships among the four aspects of mechanical properties. This paper focuses on putting forward at several problems on mechanical properties of materials that shall be concerned about during design and manufacture for nuclear pressure vessels according to ASME-BPV code. (author)

Función adrenal y metabolismo lipídico en niños asmáticos tratados con budesonida

Directory of Open Access Journals (Sweden)

Paoli-de Valeri Mariela

1999-01-01

Full Text Available Objetivo. Evaluar el efecto de bajas dosis de budesonida inhalado sobre la función adrenal y el metabolismo lipídico en niños asmáticos. Material y métodos. Se estudiaron: 10 niños asmáticos (edad promedio, 8.6 años tratados con budesonida inhalado (200-300 µg/día por un lapso mayor a tres meses (grupo A; 15 niños asmáticos (edad promedio, 7.8 años sin tratamiento esteroideo (grupo B, y 10 niños no asmáticos (grupo C. Se determinaron los niveles de cortisol basal y postestímulo con ACTH, andrógenos adrenales, lípidos y cortisol urinario. Resultados. Entre los grupos A y B no hubo diferencias significativas en las variables estudiadas. En los niños asmáticos (grupo A-B el cortisol urinario fue significativamente mayor en relación con el grupo C. Los niveles de triglicéridos, colesterol total, colesterol de la lipoproteína de baja densidad e índices aterogénicos fueron mayores en el grupo de niños asmáticos, con y sin budesonida, comparados con el grupo C. Conclusiones. El tratamiento con dosis bajas de budesonida inhalado en niños asmáticos no modificó la función del eje adrenal ni el metabolismo lipídico. Los pacientes asmáticos presentaron un perfil lipídico aterogénico que podría incrementar el riesgo de enfermedad cardiovascular.

Bibliometric Analyses Reveal Patterns of Collaboration between ASMS Members

Science.gov (United States)

Palmblad, Magnus; van Eck, Nees Jan

2018-03-01

We have explored the collaborative network of the current American Society for Mass Spectrometry (ASMS) membership using bibliometric methods. The analysis shows that 4249 members are connected in a single, large, co-authorship graph, including the majority of the most published authors in the field of mass spectrometry. The map reveals topographical differences between university groups and national laboratories, and that the co-authors with the strongest links have long worked together at the same location. We have collected and summarized information on the geographical distribution of members, showing a high coverage of active researchers in North America and Western Europe. Looking at research fields, we could also identify a number of new or `hot' topics among ASMS members. Interactive versions of the maps are available on-line at https://goo.gl/UBNFMQ (collaborative network) and https://goo.gl/WV25vm (research topics). [Figure not available: see fulltext.

The 1997 NRC IST workshops and the status of questions and issues directed to the ASME O and M committee

International Nuclear Information System (INIS)

DiBiasio, A.M.

1998-05-01

This paper describes the results of the four NRC Inservice Testing (IST) Workshops which were held in early 1997 pertaining to NRC Inspection Procedure P 73756, Inservice Testing of Pumps and Valves. It also presents the status of the ASME code committees' resolution of certain questions forwarded to the ASME by the NRC. These questions relate to code interpretations, inconsistencies in the code, and industry concerns that are most appropriately resolved through the ASME consensus process. The ASME committees reviewed the questions at their December 1997 and March 1998 code meetings. Of particular interest are those questions for which the ASME code committees did not agree with the NRC response. These questions, as well as those which the committees provided some additional insight or input, are presented in this paper

A Retrospective Look at 20 Years of ASM Education Programs (1990-2010 and a Prospective Look at the Next 20 Years (2011-2030

Directory of Open Access Journals (Sweden)

Amy Chang

2011-03-01

Full Text Available The Education Board of the American Society for Microbiology (ASM was established in the mid-1970s to address the graduate and medical education needs of ASM members. Since then, I have watched our offerings evolve from a small, graduate-level travel grant program for ASM meetings to a growing suite of professional development and networking opportunities including fellowships, publications, and conferences. Along the way, our audience has expanded from  graduate students to undergraduate biology and K-12 teachers, students of all ages, researchers, and the public.I have been fortunate enough to watch several pivotal programs and projects support our growth and change the status quo by providing opportunities for biology educators to flourish. These include the: (i Coalition for Education in the Life Sciences, (ii ASM Division on Microbiology Education, (iii ASM Conference for Undergraduate Educators, (iv ASM Journal of Microbiology & Biology Education, and (v ASM Fellowship Fund. In this review, the background and details I offer on each initiative help explain ASM Education offerings, how our growth has been supported, and where are we headed.

[Quantitative analysis of the structure of neuronal dendritic spines in the striatum using the Leitz-ASM system].

Science.gov (United States)

Leontovich, T A; Zvegintseva, E G

1985-10-01

Two principal classes of striatum long axonal neurons (sparsely ramified reticular cells and densely ramified dendritic cells) were analyzed quantitatively in four animal species: hedgehog, rabbit, dog and monkey. The cross section area, total dendritic length and the area of dendritic field were measured using "LEITZ-ASM" system. Classes of neurons studied were significantly different in dogs and monkeys, while no differences were noted between hedgehog and rabbit. Reticular neurons of different species varied much more than dendritic ones. Quantitative analysis has revealed the progressive increase in the complexity of dendritic tree in mammals from rabbit to monkey.

Airway smooth muscle cells : regulators of airway inflammation

NARCIS (Netherlands)

Zuyderduyn, Suzanne

2007-01-01

Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this

The ASME Section 11 Special Working Group On Plant Life Extension

International Nuclear Information System (INIS)

Katz, L.R.

1990-01-01

The codes and standards applicable to plant life extension have not been identified in the U.S. at this time. However, several initiatives have been taken to establish specific codes and standards pertaining to nuclear plant life extension (PLEX). One of these initiatives, sponsored by ASME, is the Section XI Special Working Group on Plant Life Extension (SWG-PLEX). The SWG-PLEX reports to the ASME Section XI Subcommittee and is responsible for recommending or drafting rules and requirements for modifying Section XI to accommodate age-related degradation to support nuclear plant life extension. This paper summarizes the results and reports the activities of the SWG-PLEX during the 1989/1990 period

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

Energy Technology Data Exchange (ETDEWEB)

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R. (Sanofi Aventis); (UMASS, Amherst)

2016-10-26

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.

Creep-fatigue damage evaluation for SS-316LN (ORNL PLATES): - RCC-MR vs. ASME SEC III - NH

International Nuclear Information System (INIS)

Sati, Bhuwan Chandra; Jalaldeen, S.; Velusamy, K.; Selvaraj, P.

2016-01-01

Investigations of high temperature tests done on ORNL plate with deformation control loading, under creep-fatigue damage have been presented. The test results with methodology of RCC-MR and ASME-NH life prediction under creep-fatigue loading have been assessed. The stress relaxation effect in calculating the life using RCC-MR under creep-fatigue damage is found to be significant in presence of secondary stress. RCC-MR: 2007 is more realistic number of cycles (predicts 51 number of cycles) as compared to ASME-NH (predicts 312 number of cycles) which is demonstrated by the experimental work (observed 86 numbers of cycles). Between RCC-MR and experimental work, design code seems to be more conservative for life prediction due to creep-fatigue damage. For fatigue damage, the approaches are same and the difference comes from material properties and the starting stress for applying Neuber's rule. ASME approach has the limitation of stress range magnitude. ASME approach predicts lower elastic plus plastic strain for the cases having S* above the linear stress limit. For creep strain and creep damage evaluation, ASME and RCC-MR have different approaches for calculating the stress at the beginning and during the hold period. The RCC-MR takes account of cyclic hardening or softening effects (hardening in the present case of 316 LN) by means of the cyclic stress-strain curve and the benefit of symmetrization effects which are significant for this material. The ASME code neglects these effects and instead relies on an approach based on the isochronous stress-strain curves. (author)

A study on technical issues of materials and design bases in ASME section III subsection NH code

International Nuclear Information System (INIS)

Lee, Hyeong Yeon; Kim, Jong Bum; Yoo, Bong

2000-12-01

In this study, an analysis of evaluation report by ORNL on the technical issues of elevated temperatures design guide line, ASME Code Section III Subsection NH was conducted and a brief evaluation procedure of the creep-fatigue damage was presented. ORNL published the report in 1993 and reviewed the issue areas where code rules or regulatory guides may be lacking or inadequate to ensure safe operation over the expected life cycles for liquid metal reactor systems. From historical viewpoint of the ASME NH code development, ASME Code Case 47 was changed much in 1989 edition, which includes the stress relaxation behavior in creep damage evaluation. Afterwards the 1992 version of CC N-47 was upgraded to Subsection NH in 1995 edition, which is the same with that of CC N-47 1992 edition except few material data. This report brings up the technical and regulatory issues that can not guarantee the safe and reliable operation of the ALMR which got the conceptual design certification from NRC. Twenty three technical issues were raised and settlement methodology were proposed. Additionally, the status of items approved by ASME code subgroup of elevated temperature design committee for the revision of the most recent 1998 edition of ASME NH was described

ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

Directory of Open Access Journals (Sweden)

Yongsoon Kim

Full Text Available In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

Science.gov (United States)

Kim, Yongsoon; Sun, Hong

2012-01-01

In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

Science.gov (United States)

Kim, Yongsoon; Sun, Hong

2012-01-01

In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

Abelian Sandpile Model (ASM) and Infinite Volume Limit

Indian Academy of Sciences (India)

ASM- Properties. Any possible sequence of topplings leads to the same stable configuration [Dhar]. The result of particle addition at and subsequent relaxation is given by an operator. £ бвд £ евд £. , where вд £. ¢. ¦. ¤ззз ¤ вг иг . £. ©. ¢ йа£. (Abelian). 7-b ...

46 CFR 53.01-3 - Adoption of section IV of the ASME Boiler and Pressure Vessel Code.

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of section IV of the ASME Boiler and Pressure...) MARINE ENGINEERING HEATING BOILERS General Requirements § 53.01-3 Adoption of section IV of the ASME Boiler and Pressure Vessel Code. (a) Heating boilers shall be designed, constructed, inspected, tested...

46 CFR 52.01-2 - Adoption of section I of the ASME Boiler and Pressure Vessel Code.

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of section I of the ASME Boiler and Pressure...) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-2 Adoption of section I of the ASME Boiler and Pressure Vessel Code. (a) Main power boilers and auxiliary boilers shall be designed, constructed...

Estimates of the burst reliability of thin-walled cylinders designed to meet the ASME Code allowables

International Nuclear Information System (INIS)

Stancampiano, P.A.; Zemanick, P.P.

1976-01-01

Pressure containment components in nuclear power plants are designed by the conventional deterministic safety factor approach to meet the requirements of the ASME Pressure Vessel Code, Section III. The inevitable variabilities and uncertainties associated with the design, manufacture, installation, and service processes suggest a probabilistic design approach may also be pertinent. Accordingly, the burst reliabilities of two thin-walled 304 SS cylindrical vessels such as might be employed in liquid metal plants are estimated. A large vessel fabricated from rolled plate per ASME SA-240 and a smaller pipe sized vessel also fabricated from rolled plate per ASME SA-358 are considered. The vessels are sized to just meet the allowable ASME Code primary membrance stresses at 800 0 F (427 0 C). The bursting probability that the operating pressure is greater than the burst strength of the cylinders is calculated using stress-strength interference theory by direct Monte Carlo simulation on a high speed digital computer. A sensitivity study is employed to identify those design parameters which have the greatest effect on the reliability. The effects of preservice quality assurance defect inspections on the reliability are also evaluated parametrically

A Survey of Variable Extragalactic Sources with XTE's All Sky Monitor (ASM)

Science.gov (United States)

Jernigan, Garrett

1998-01-01

The original goal of the project was the near real-time detection of AGN utilizing the SSC 3 of the ASM on XTE which does a deep integration on one 100 square degree region of the sky. While the SSC never performed sufficiently well to allow the success of this goal, the work on the project has led to the development of a new analysis method for coded aperture systems which has now been applied to ASM data for mapping regions near clusters of galaxies such as the Perseus Cluster and the Coma Cluster. Publications are in preparation that describe both the new method and the results from mapping clusters of galaxies.

Suppression of the increasing level of acetylcholine-stimulated intracellular Ca2+ in guinea pig airway smooth muscle cells by mabuterol.

Science.gov (United States)

Song, Xirui; Zhao, Chao; Dai, Cailing; Ren, Yanxin; An, Nan; Wen, Huimin; Pan, L I; Cheng, Maosheng; Zhang, Yuyang

2015-11-01

The present study aimed to establish an effective method for the in vitro culture of guinea pig airway smooth muscle (ASM) cells, and also investigate the suppressive effect of mabuterol hydrochloride (Mab) on the increased level of intracellular Ca 2+ in ASM cells induced with acetylcholine (Ach). Two different methods, i.e. with or without collagenase to pretreat tracheal tissues, were applied to the manufacture of ASM cells. Cell viability was determined with the 3-(4,5-dimethylthinazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunocytochemistry and immunofluorescence were used for the identification of ASM cells. Different concentration levels (10 -3 , 10 -4 , 10 -5 , 10 -6 and 10 -7 mmol/l) of Mab were administered 5 min before Ach (10 -4 M) treatment, respectively. The Ca 2+ fluorescent probe, Fura-2/AM or Fluo-3/AM were applied to the inspection of Ca 2+ fluorescent intensity with Varioskan Flash, immunocytometry systems and an inverted system microscope, respectively. The results showed that the fresh method, in which isolated tracheal tissues were previously treated with collagenase for 20 min, was more advantageous for the preparation of guinea pig ASM cells compared to when the enzyme was not used. The time for the ASM cells to initially migrate out of the 'tissue blocks' and the culture having to be generated due to the thick cell density was significantly less. On identification with immunocytochemistry or immunofluorescent staining, >95% of the cells were ASM cells. Mab (10 -3 -10 -7 mmol/l) significantly suppressed the elevation of intracellular Ca 2+ induced by Ach in a concentration-dependent manner. The inhibitory rates of intracellular Ca 2+ by different concentrations of Mab, from low to high, were 14.93, 24.73, 40.06, 48.54 and 57.13%, respectively, when Varioskan Flash was used for determination. In conclusion, this novel method has a shorter harvesting period for ASM cells. Mab can suppress the increasing level of intracellular Ca 2

Assessment of induction elbows for an ASME Code application

International Nuclear Information System (INIS)

Panesar, J.S.; Soliman, M.

1991-01-01

The ASME Nuclear Codes impose some specific requirements on the wall thickness uniformity and the out-of-roundness of cross sections of the elbows for Nuclear Power Plant applications. Due to some of these requirements, manufacturing and installation of these elbows can be time consuming and quite expensive. This paper explores the feasibility of using induction elbows for nuclear application from the stress analysis point of view. To this end, three different sizes of 90deg elbows have been analyzed based on the geometry of an 'ASME Code' elbow and an elbow formed by induction bending. The analysis is carried out for internal pressure, in-plane and out-of-plane loads. Based on the results of these three carbon steel elbows, the use of induction elbows in some of the CANDU-PHW (CANadian Deuterium Uranium-Pressurized Heavy Water) power plant applications seems encouraging. However, before the feasibility can be fully confirmed analysis and induction bending tests over a wider range of geometries, loading conditions, and materials are required. (author)

Utilização de Ecolife® e Acibenzolar-s-metil (ASM no controle da antracnose da banana em pós-colheita Use of Ecolife® and Acibenzolar-S-metil (ASM on the control of antracnosis in banana post-harvest

Directory of Open Access Journals (Sweden)

Luciano Marinho Furtado

2010-09-01

Full Text Available O objetivo deste trabalho foi avaliar a ação dos produtos ASM e Ecolife no controle da antracnose pós-colheita em frutos de banana. Frutos sadios de banana, variedades maçã, prata, pacovan e cacau , em fase intermediária de maturação, foram imersos previamente em soluções de ASM e Ecolife e inoculados com Colletotrichum musae. Utilizou-se o delineamento inteiramente casualizado, em esquema fatorial com quatro repetições. Os resultados apresentados demonstraram a eficácia dos produtos nas concentrações de 5 ml/ L (Ecolife e 0,50g/ L (ASM no controle da antracnose nas variedades analisa das. A variedade cacau apresentou menor lesão quando tratada com o Ecolife (5,79 mm. Com relação ao efeito do ASM, a bana na prata demonstrou um melhor resultado, com tamanho médio de lesão de 5,62 mm. Com o decorrer do processo de maturação dos frutos houve um decréscimo na severidade da doença nas quatro variedades estudadas, exceto no tratamento testemunha, que continuou apresentando aumento no tamanho das lesões nos frutos e atingir a polpa ao final da maturação.The aim of this work was to evaluate the effects of ASM and Ecolife on the control of post-harvest antracnosis in banana. Banana fruits of Maçã, Prata, Pacovan and Figo varieties, at intermediate stage of maturation, were immersed in solutions of ASM and Ecolife and inoculated with Colletotrichum musae A completely randomized design was used, at a factorial scheme 4x2 (four varieties x two products with four replicates. The presented results demonstrated the susceptibility of the fruits to the disease, mainly Maça variety with lesion of 17,99 mm. It was demosntrated the effectiveness of products at concentrations of 5ml. L-1 (Ecolife and 0.50g. L-1 (ASM on antracnosis control. The Figo variety presented the smallest injuries when treated with Ecolife (5.79 mm. Regarding ASM effects, Prata variety demonstrated the best performance, with 5.62 mm of injuries diameter

Roles of acid sphingomyelinase activation in neuronal cells apoptosis induced by microwave irradiation

International Nuclear Information System (INIS)

Zhang Lei; Xu Shangcheng; Zhang Guangbin; Yu Zhengping

2009-01-01

The present study is to examine the effect of microwave on acid sphingomyelinase (ASM) activity and expression, and to explore the role of ASM activation in neuronal cells apoptosis induced by microwave irradiation. Primary cultured hippocampal neurons were irradiated by 30 W/cm 2 microwave for 10 min, and ASM activity assay was used to investigate ASM activity alteration. RT-PCR and western blot were used to detect ASM mRNA and protein expression respectively. Apoptosis was observed by Hoechst 33342 fluorescence staining. ASM specific inhibitor imipramine was applied to inhibit ASM activation. It has been found that apoptosis rate of primary cultured hippocampal neurons increased significantly after microwave irradiation. ASM was activated while ASM mRNA and protein expression were upregulated in neurons after microwave irradiation. Pretreatment with imipramine could reverse neuronal apoptosis induced by microwave irradiation. Results show that microwave irradiation causes increment of ASM activation and expression and ASM activation is involved in microwave induced neuronal apoptosis. (authors)

Recommendations to ASME for code guidelines and criteria for continued operation of equipment

International Nuclear Information System (INIS)

Harvey, J.F.

1993-01-01

In May 1988, the American Society of Mechanical Engineers, ASME, asked the Pressure Vessel Research Council, PVRC, to review the part it should play in the continued operation of equipment originally designed and fabricated to the ASME codes and rules. This was prompted solely by an economic opportunity in which the capital expenditures to replace plants was far more costly than evaluating, repairing, and extending the nominal design life of the individual component. For instance, nuclear plants are normally designed for a life of 40 years, while fossil fired facilities may have been designed for other time lives, yet at the end of their original design life may actually have many useful years remaining. While this action was economically prompted, it inherently involved a two-fold one; namely, (1) safety, (2) legal. There is no question of safety to operating personnel. While codes for fossil components do not specify design lives, their adoption by many states provides a legal means of procedure in event of a mishap. This recognizes a cradle-to-grave safety responsibility. It is toward maintaining ASMEs leadership as a code authority that this report has been prepared

Targeting Phosphoinositide 3-Kinase γ in Airway Smooth Muscle Cells to Suppress Interleukin-13-Induced Mouse Airway Hyperresponsiveness

Science.gov (United States)

Jiang, Haihong; Xie, Yan; Abel, Peter W.; Toews, Myron L.; Townley, Robert G.; Casale, Thomas B.

2012-01-01

We recently reported that phosphoinositide 3-kinase γ (PI3Kγ) directly regulates airway smooth muscle (ASM) contraction by modulating Ca2+ oscillations. Because ASM contraction plays a critical role in airway hyperresponsiveness (AHR) of asthma, the aim of the present study was to determine whether targeting PI3Kγ in ASM cells could suppress AHR in vitro and in vivo. Intranasal administration into mice of interleukin-13 (IL-13; 10 μg per mouse), a key pathophysiologic cytokine in asthma, induced AHR after 48 h, as assessed by invasive tracheostomy. Intranasal administration of a broad-spectrum PI3K inhibitor or a PI3Kγ-specific inhibitor 1 h before AHR assessment attenuated IL-13 effects. Airway responsiveness to bronchoconstrictor agonists was also examined in precision-cut mouse lung slices pretreated without or with IL-13 for 24 h. Acetylcholine and serotonin dose-response curves indicated that IL-13-treated lung slices had a 40 to 50% larger maximal airway constriction compared with controls. Furthermore, acetylcholine induced a larger initial Ca2+ transient and increased Ca2+ oscillations in IL-13-treated primary mouse ASM cells compared with control cells, correlating with increased cell contraction. As expected, PI3Kγ inhibitor treatment attenuated IL-13-augmented airway contractility of lung slices and ASM cell contraction. In both control and IL-13-treated ASM cells, small interfering RNA-mediated knockdown of PI3Kγ by 70% only reduced the initial Ca2+ transient by 20 to 30% but markedly attenuated Ca2+ oscillations and contractility of ASM cells by 50 to 60%. This report is the first to demonstrate that PI3Kγ in ASM cells is important for IL-13-induced AHR and that acute treatment with a PI3Kγ inhibitor can ameliorate AHR in a murine model of asthma. PMID:22543031

ASM Based Synthesis of Handwritten Arabic Text Pages

Directory of Open Access Journals (Sweden)

Laslo Dinges

2015-01-01

Full Text Available Document analysis tasks, as text recognition, word spotting, or segmentation, are highly dependent on comprehensive and suitable databases for training and validation. However their generation is expensive in sense of labor and time. As a matter of fact, there is a lack of such databases, which complicates research and development. This is especially true for the case of Arabic handwriting recognition, that involves different preprocessing, segmentation, and recognition methods, which have individual demands on samples and ground truth. To bypass this problem, we present an efficient system that automatically turns Arabic Unicode text into synthetic images of handwritten documents and detailed ground truth. Active Shape Models (ASMs based on 28046 online samples were used for character synthesis and statistical properties were extracted from the IESK-arDB database to simulate baselines and word slant or skew. In the synthesis step ASM based representations are composed to words and text pages, smoothed by B-Spline interpolation and rendered considering writing speed and pen characteristics. Finally, we use the synthetic data to validate a segmentation method. An experimental comparison with the IESK-arDB database encourages to train and test document analysis related methods on synthetic samples, whenever no sufficient natural ground truthed data is available.

ASM Based Synthesis of Handwritten Arabic Text Pages.

Science.gov (United States)

Dinges, Laslo; Al-Hamadi, Ayoub; Elzobi, Moftah; El-Etriby, Sherif; Ghoneim, Ahmed

2015-01-01

Document analysis tasks, as text recognition, word spotting, or segmentation, are highly dependent on comprehensive and suitable databases for training and validation. However their generation is expensive in sense of labor and time. As a matter of fact, there is a lack of such databases, which complicates research and development. This is especially true for the case of Arabic handwriting recognition, that involves different preprocessing, segmentation, and recognition methods, which have individual demands on samples and ground truth. To bypass this problem, we present an efficient system that automatically turns Arabic Unicode text into synthetic images of handwritten documents and detailed ground truth. Active Shape Models (ASMs) based on 28046 online samples were used for character synthesis and statistical properties were extracted from the IESK-arDB database to simulate baselines and word slant or skew. In the synthesis step ASM based representations are composed to words and text pages, smoothed by B-Spline interpolation and rendered considering writing speed and pen characteristics. Finally, we use the synthetic data to validate a segmentation method. An experimental comparison with the IESK-arDB database encourages to train and test document analysis related methods on synthetic samples, whenever no sufficient natural ground truthed data is available.

Towards a consensus-based biokinetic model for green microalgae – The ASM-A

DEFF Research Database (Denmark)

Wágner, Dorottya Sarolta; Valverde Pérez, Borja; Sæbø, Mariann

2016-01-01

developed to predict microalgal growth. However, none of these models can effectively describe all the relevant processes when microalgal growth is coupled with nutrient removal and recovery from wastewaters. Here, we present a mathematical model developed to simulate green microalgal growth (ASM-A) using...... and substrate availability can introduce significant variability on parameter values for predicting the reaction rates for bulk nitrate and the intracellularly stored nitrogen state-variables, thereby requiring scenario specific model calibration. ASM-A was identified using standard cultivation medium...

Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

Directory of Open Access Journals (Sweden)

Aihua Hu

Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

Application of adjusted subpixel method (ASM) in HRCT measurements of the bronchi in bronchial asthma patients and healthy individuals.

Science.gov (United States)

Mincewicz, Grzegorz; Rumiński, Jacek; Krzykowski, Grzegorz

2012-02-01

Recently, we described a model system which included corrections of high-resolution computed tomography (HRCT) bronchial measurements based on the adjusted subpixel method (ASM). To verify the clinical application of ASM by comparing bronchial measurements obtained by means of the traditional eye-driven method, subpixel method alone and ASM in a group comprised of bronchial asthma patients and healthy individuals. The study included 30 bronchial asthma patients and the control group comprised of 20 volunteers with no symptoms of asthma. The lowest internal and external diameters of the bronchial cross-sections (ID and ED) and their derivative parameters were determined in HRCT scans using: (1) traditional eye-driven method, (2) subpixel technique, and (3) ASM. In the case of the eye-driven method, lower ID values along with lower bronchial lumen area and its percentage ratio to total bronchial area were basic parameters that differed between asthma patients and healthy controls. In the case of the subpixel method and ASM, both groups were not significantly different in terms of ID. Significant differences were observed in values of ED and total bronchial area with both parameters being significantly higher in asthma patients. Compared to ASM, the eye-driven method overstated the values of ID and ED by about 30% and 10% respectively, while understating bronchial wall thickness by about 18%. Results obtained in this study suggest that the traditional eye-driven method of HRCT-based measurement of bronchial tree components probably overstates the degree of bronchial patency in asthma patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Application of adjusted subpixel method (ASM) in HRCT measurements of the bronchi in bronchial asthma patients and healthy individuals

International Nuclear Information System (INIS)

Mincewicz, Grzegorz; Rumiński, Jacek; Krzykowski, Grzegorz

2012-01-01

Background: Recently, we described a model system which included corrections of high-resolution computed tomography (HRCT) bronchial measurements based on the adjusted subpixel method (ASM). Objective: To verify the clinical application of ASM by comparing bronchial measurements obtained by means of the traditional eye-driven method, subpixel method alone and ASM in a group comprised of bronchial asthma patients and healthy individuals. Methods: The study included 30 bronchial asthma patients and the control group comprised of 20 volunteers with no symptoms of asthma. The lowest internal and external diameters of the bronchial cross-sections (ID and ED) and their derivative parameters were determined in HRCT scans using: (1) traditional eye-driven method, (2) subpixel technique, and (3) ASM. Results: In the case of the eye-driven method, lower ID values along with lower bronchial lumen area and its percentage ratio to total bronchial area were basic parameters that differed between asthma patients and healthy controls. In the case of the subpixel method and ASM, both groups were not significantly different in terms of ID. Significant differences were observed in values of ED and total bronchial area with both parameters being significantly higher in asthma patients. Compared to ASM, the eye-driven method overstated the values of ID and ED by about 30% and 10% respectively, while understating bronchial wall thickness by about 18%. Conclusions: Results obtained in this study suggest that the traditional eye-driven method of HRCT-based measurement of bronchial tree components probably overstates the degree of bronchial patency in asthma patients.

Feature extraction for face recognition via Active Shape Model (ASM) and Active Appearance Model (AAM)

Science.gov (United States)

Iqtait, M.; Mohamad, F. S.; Mamat, M.

2018-03-01

Biometric is a pattern recognition system which is used for automatic recognition of persons based on characteristics and features of an individual. Face recognition with high recognition rate is still a challenging task and usually accomplished in three phases consisting of face detection, feature extraction, and expression classification. Precise and strong location of trait point is a complicated and difficult issue in face recognition. Cootes proposed a Multi Resolution Active Shape Models (ASM) algorithm, which could extract specified shape accurately and efficiently. Furthermore, as the improvement of ASM, Active Appearance Models algorithm (AAM) is proposed to extracts both shape and texture of specified object simultaneously. In this paper we give more details about the two algorithms and give the results of experiments, testing their performance on one dataset of faces. We found that the ASM is faster and gains more accurate trait point location than the AAM, but the AAM gains a better match to the texture.

3D automatic anatomy segmentation based on iterative graph-cut-ASM.

Science.gov (United States)

Chen, Xinjian; Bagci, Ulas

2011-08-01

This paper studies the feasibility of developing an automatic anatomy segmentation (AAS) system in clinical radiology and demonstrates its operation on clinical 3D images. The AAS system, the authors are developing consists of two main parts: object recognition and object delineation. As for recognition, a hierarchical 3D scale-based multiobject method is used for the multiobject recognition task, which incorporates intensity weighted ball-scale (b-scale) information into the active shape model (ASM). For object delineation, an iterative graph-cut-ASM (IGCASM) algorithm is proposed, which effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. The presented IGCASM algorithm is a 3D generalization of the 2D GC-ASM method that they proposed previously in Chen et al. [Proc. SPIE, 7259, 72590C1-72590C-8 (2009)]. The proposed methods are tested on two datasets comprised of images obtained from 20 patients (10 male and 10 female) of clinical abdominal CT scans, and 11 foot magnetic resonance imaging (MRI) scans. The test is for four organs (liver, left and right kidneys, and spleen) segmentation, five foot bones (calcaneus, tibia, cuboid, talus, and navicular). The recognition and delineation accuracies were evaluated separately. The recognition accuracy was evaluated in terms of translation, rotation, and scale (size) error. The delineation accuracy was evaluated in terms of true and false positive volume fractions (TPVF, FPVF). The efficiency of the delineation method was also evaluated on an Intel Pentium IV PC with a 3.4 GHZ CPU machine. The recognition accuracies in terms of translation, rotation, and scale error over all organs are about 8 mm, 10 degrees and 0.03, and over all foot bones are about 3.5709 mm, 0.35 degrees and 0.025, respectively. The accuracy of delineation over all organs for all subjects as expressed in TPVF and FPVF is 93.01% and 0.22%, and all foot bones for

3D automatic anatomy segmentation based on iterative graph-cut-ASM

International Nuclear Information System (INIS)

Chen, Xinjian; Bagci, Ulas

2011-01-01

Purpose: This paper studies the feasibility of developing an automatic anatomy segmentation (AAS) system in clinical radiology and demonstrates its operation on clinical 3D images. Methods: The AAS system, the authors are developing consists of two main parts: object recognition and object delineation. As for recognition, a hierarchical 3D scale-based multiobject method is used for the multiobject recognition task, which incorporates intensity weighted ball-scale (b-scale) information into the active shape model (ASM). For object delineation, an iterative graph-cut-ASM (IGCASM) algorithm is proposed, which effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. The presented IGCASM algorithm is a 3D generalization of the 2D GC-ASM method that they proposed previously in Chen et al.[Proc. SPIE, 7259, 72590C1-72590C-8 (2009)]. The proposed methods are tested on two datasets comprised of images obtained from 20 patients (10 male and 10 female) of clinical abdominal CT scans, and 11 foot magnetic resonance imaging (MRI) scans. The test is for four organs (liver, left and right kidneys, and spleen) segmentation, five foot bones (calcaneus, tibia, cuboid, talus, and navicular). The recognition and delineation accuracies were evaluated separately. The recognition accuracy was evaluated in terms of translation, rotation, and scale (size) error. The delineation accuracy was evaluated in terms of true and false positive volume fractions (TPVF, FPVF). The efficiency of the delineation method was also evaluated on an Intel Pentium IV PC with a 3.4 GHZ CPU machine. Results: The recognition accuracies in terms of translation, rotation, and scale error over all organs are about 8 mm, 10 deg. and 0.03, and over all foot bones are about 3.5709 mm, 0.35 deg. and 0.025, respectively. The accuracy of delineation over all organs for all subjects as expressed in TPVF and FPVF is 93.01% and 0.22%, and

Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models.

Science.gov (United States)

Lew, D Betty; Michael, Christie F; Overbeck, Tracie; Robinson, W Scout; Rohman, Erin L; Lehman, Jeffrey M; Patel, Jennifer K; Eiseman, Brandi; LeMessurier, Kim S; Samarasinghe, Amali E; Gaber, M Waleed

2017-01-01

One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models

Directory of Open Access Journals (Sweden)

D. Betty Lew

2017-01-01

Full Text Available One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM remodeling effects. The mannose receptor (MR family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR and that mannan derived from Saccharomyces cerevisiae (SC-MN inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2 expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

Low appendicular skeletal muscle mass (ASM) with limited mobility and poor health outcomes in middle-aged African Americans.

Science.gov (United States)

Malmstrom, Theodore K; Miller, Douglas K; Herning, Margaret M; Morley, John E

2013-09-01

Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical syndrome associated with the loss of both skeletal muscle mass and muscle function that occurs with aging. Validation of sarcopenia definitions that include both low muscle mass and poor muscle function is needed. In the population-based African American Health (AAH) study (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4 (2004). Muscle mass was measured using dual energy x-ray absorptiometry and mobility by a 6-min walk test and 4-m gait walk test. Height corrected appendicular skeletal mass (ASM; 9.0 ± 1.5 in n = 124 males, 8.3 ± 2.2 in n = 195 females) was computed as total lean muscle mass in arms and legs (kilograms) divided by the square of height (meters). Cross-sectional and longitudinal (6-year) associations of low ASM (bottom 25 % AAH sample; ASM with limited mobility (4-m gait walk ≤1 m/s or 6-min walk ASM with limited mobility was associated with IADL difficulties (p = .008) and frailty (p = .040) but not with ADL difficulties or falls in cross-sectional analyses; and with ADL difficulties (p = .022), IADL difficulties (p = .006), frailty (p = .039), and mortality (p = .003) but not with falls in longitudinal analyses adjusted for age and gender. Low ASM alone was marginally associated with mortality (p = .085) but not with other outcomes in cross-sectional or longitudinal analyses. Low ASM with limited mobility is associated with poor health outcomes among late middle-aged African Americans.

Atypical Squamous Cells in Liquid-Based Cervical Cytology: Microbiology, Inflammatory Infiltrate, and Human Papillomavirus-DNA Testing.

Science.gov (United States)

Gomes de Oliveira, Geilson; Eleutério, Renata Mirian Nunes; Silveira Gonçalves, Ana Katherine; Giraldo, Paulo César; Eleutério, José

2018-01-01

The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology. © 2017 S. Karger AG, Basel.

Comparative evaluation of structural integrity for ITER blanket shield block based on SDC-IC and ASME code

Energy Technology Data Exchange (ETDEWEB)

Shim, Hee-Jin [ITER Korea, National Fusion Research Institute, 169-148 Gwahak-Ro, Yuseong-Gu, Daejeon (Korea, Republic of); Ha, Min-Su, E-mail: msha12@nfri.re.kr [ITER Korea, National Fusion Research Institute, 169-148 Gwahak-Ro, Yuseong-Gu, Daejeon (Korea, Republic of); Kim, Sa-Woong; Jung, Hun-Chea [ITER Korea, National Fusion Research Institute, 169-148 Gwahak-Ro, Yuseong-Gu, Daejeon (Korea, Republic of); Kim, Duck-Hoi [ITER Organization, Route de Vinon sur Verdon - CS 90046, 13067 Sant Paul Lez Durance (France)

2016-11-01

Highlights: • The procedure of structural integrity and fatigue assessment was described. • Case studies were performed according to both SDC-IC and ASME Sec. • III codes The conservatism of the ASME code was demonstrated. • The study only covers the specifically comparable case about fatigue usage factor. - Abstract: The ITER blanket Shield Block is a bulk structure to absorb radiation and to provide thermal shielding to vacuum vessel and external vessel components, therefore the most significant load for Shield Block is the thermal load. In the previous study, the thermo-mechanical analysis has been performed under the inductive operation as representative loading condition. And the fatigue evaluations were conducted to assure structural integrity for Shield Block according to Structural Design Criteria for In-vessel Components (SDC-IC) which provided by ITER Organization (IO) based on the code of RCC-MR. Generally, ASME code (especially, B&PV Sec. III) is widely applied for design of nuclear components, and is usually well known as more conservative than other specific codes. For the view point of the fatigue assessment, ASME code is very conservative compared with SDC-IC in terms of the reflected K{sub e} factor, design fatigue curve and other factors. Therefore, an accurate fatigue assessment comparison is needed to measure of conservatism. The purpose of this study is to provide the fatigue usage comparison resulting from the specified operating conditions shall be evaluated for Shield Block based on both SDC-IC and ASME code, and to discuss the conservatism of the results.

Comparative evaluation of structural integrity for ITER blanket shield block based on SDC-IC and ASME code

International Nuclear Information System (INIS)

Shim, Hee-Jin; Ha, Min-Su; Kim, Sa-Woong; Jung, Hun-Chea; Kim, Duck-Hoi

2016-01-01

Highlights: • The procedure of structural integrity and fatigue assessment was described. • Case studies were performed according to both SDC-IC and ASME Sec. • III codes The conservatism of the ASME code was demonstrated. • The study only covers the specifically comparable case about fatigue usage factor. - Abstract: The ITER blanket Shield Block is a bulk structure to absorb radiation and to provide thermal shielding to vacuum vessel and external vessel components, therefore the most significant load for Shield Block is the thermal load. In the previous study, the thermo-mechanical analysis has been performed under the inductive operation as representative loading condition. And the fatigue evaluations were conducted to assure structural integrity for Shield Block according to Structural Design Criteria for In-vessel Components (SDC-IC) which provided by ITER Organization (IO) based on the code of RCC-MR. Generally, ASME code (especially, B&PV Sec. III) is widely applied for design of nuclear components, and is usually well known as more conservative than other specific codes. For the view point of the fatigue assessment, ASME code is very conservative compared with SDC-IC in terms of the reflected K_e factor, design fatigue curve and other factors. Therefore, an accurate fatigue assessment comparison is needed to measure of conservatism. The purpose of this study is to provide the fatigue usage comparison resulting from the specified operating conditions shall be evaluated for Shield Block based on both SDC-IC and ASME code, and to discuss the conservatism of the results.

ASME AG-1 Section FC Qualified HEPA Filters; a Particle Loading Comparison - 13435

International Nuclear Information System (INIS)

Stillo, Andrew; Ricketts, Craig I.

2013-01-01

High Efficiency Particulate Air (HEPA) Filters used to protect personnel, the public and the environment from airborne radioactive materials are designed, manufactured and qualified in accordance with ASME AG-1 Code section FC (HEPA Filters) [1]. The qualification process requires that filters manufactured in accordance with this ASME AG-1 code section must meet several performance requirements. These requirements include performance specifications for resistance to airflow, aerosol penetration, resistance to rough handling, resistance to pressure (includes high humidity and water droplet exposure), resistance to heated air, spot flame resistance and a visual/dimensional inspection. None of these requirements evaluate the particle loading capacity of a HEPA filter design. Concerns, over the particle loading capacity, of the different designs included within the ASME AG-1 section FC code[1], have been voiced in the recent past. Additionally, the ability of a filter to maintain its integrity, if subjected to severe operating conditions such as elevated relative humidity, fog conditions or elevated temperature, after loading in use over long service intervals is also a major concern. Although currently qualified HEPA filter media are likely to have similar loading characteristics when evaluated independently, filter pleat geometry can have a significant impact on the in-situ particle loading capacity of filter packs. Aerosol particle characteristics, such as size and composition, may also have a significant impact on filter loading capacity. Test results comparing filter loading capacities for three different aerosol particles and three different filter pack configurations are reviewed. The information presented represents an empirical performance comparison among the filter designs tested. The results may serve as a basis for further discussion toward the possible development of a particle loading test to be included in the qualification requirements of ASME AG-1

ASME AG-1 Section FC Qualified HEPA Filters; a Particle Loading Comparison - 13435

Energy Technology Data Exchange (ETDEWEB)

Stillo, Andrew [Camfil Farr, 1 North Corporate Drive, Riverdale, NJ 07457 (United States); Ricketts, Craig I. [New Mexico State University, Department of Engineering Technology and Surveying Engineering, P.O. Box 30001 MSC 3566, Las Cruces, NM 88003-8001 (United States)

2013-07-01

High Efficiency Particulate Air (HEPA) Filters used to protect personnel, the public and the environment from airborne radioactive materials are designed, manufactured and qualified in accordance with ASME AG-1 Code section FC (HEPA Filters) [1]. The qualification process requires that filters manufactured in accordance with this ASME AG-1 code section must meet several performance requirements. These requirements include performance specifications for resistance to airflow, aerosol penetration, resistance to rough handling, resistance to pressure (includes high humidity and water droplet exposure), resistance to heated air, spot flame resistance and a visual/dimensional inspection. None of these requirements evaluate the particle loading capacity of a HEPA filter design. Concerns, over the particle loading capacity, of the different designs included within the ASME AG-1 section FC code[1], have been voiced in the recent past. Additionally, the ability of a filter to maintain its integrity, if subjected to severe operating conditions such as elevated relative humidity, fog conditions or elevated temperature, after loading in use over long service intervals is also a major concern. Although currently qualified HEPA filter media are likely to have similar loading characteristics when evaluated independently, filter pleat geometry can have a significant impact on the in-situ particle loading capacity of filter packs. Aerosol particle characteristics, such as size and composition, may also have a significant impact on filter loading capacity. Test results comparing filter loading capacities for three different aerosol particles and three different filter pack configurations are reviewed. The information presented represents an empirical performance comparison among the filter designs tested. The results may serve as a basis for further discussion toward the possible development of a particle loading test to be included in the qualification requirements of ASME AG-1

ASME Evaluation on Grid Mobile E-Commerce Process

OpenAIRE

Dan Chang; Wei Liao

2012-01-01

With the development of E-commerce, more scholars have paid attention to research on Mobile E-commerce and mostly focus on the optimization and evaluation of existing process. This paper researches the evaluation of Mobile E-commerce process with a method called ASME. Based on combing and analyzing current mobile business process and utilizing the grid management theory, mobile business process based on grid are constructed. Firstly, the existing process, namely Non-grid Mobile E-commerce, an...

Conservatism of ASME KIR-reference curve with respect to crack arrest

International Nuclear Information System (INIS)

Wallin, K.; Rintamaa, R.; Nagel, G.

1999-01-01

The conservatism of the RT NDT temperature indexing parameter and the ASME K IR -reference curve with respect to crack arrest toughness, has been evaluated. Based on an analysis of the original ASME K Ia data, it was established that inherently, the ASME K IR -reference curve corresponds to an overall 5% lower bound curve with respect to crack arrest. It was shown that the scatter of crack arrest toughness is essentially material independent and has a standard deviation of 18% and the temperature dependence of K Ia has the same form as predicted by the master curve for crack initiation toughness. The 'built in' offset between the mean 100 MPa√(m) crack arrest temperature, TK Ia , and RT NDT is 38 C (TK Ia =RT NDT +38 C) and the experimental relation between TK Ia and NDT is, TK Ia =NDT+28 C. The K IR -reference curve using NDT as reference temperature will be conservative with respect to the general 5% lower bound K Ia(5%) -curve, with a 75% confidence. The use of RT NDT , instead of NDT, will generally increase the degree of conservatism, both for non-irradiated as well as irradiated materials, close to a 95% confidence level. This trend is pronounced for materials with Charpy-V upper shelf energies below 100 J. It is shown that the K IR -curve effectively constitutes a deterministic lower bound curve for crack arrest. The findings are valid both for nuclear pressure vessel plates, forgings and welds. (orig.)

Conservatism of ASME KIR-reference curve with respect to crack arrest

International Nuclear Information System (INIS)

Wallin, K.; Rintamaa, R.; Nagel, G.

2001-01-01

The conservatism of the RT NDT temperature indexing parameter and the ASME K IR -reference curve with respect to crack arrest toughness, has been evaluated. Based on an analysis of the original ASME K Ia data, it was established that inherently, the ASME K IR -reference curve corresponds to an overall 5% lower bound curve with respect to crack arrest. It was shown that the scatter of crack arrest toughness is essentially material independent and has a standard deviation (S.D.) of 18% and the temperature dependence of K Ia has the same form as predicted by the master curve for crack initiation toughness. The 'built in' offset between the mean 100 MPa√m crack arrest temperature, TK Ia , and RT NDT is 38 deg. C (TK Ia =RT NDT +38 deg. C) and the experimental relation between TK Ia and NDT is, TK Ia =NDT+28 deg. C. The K IR -reference curve using NDT as reference temperature will be conservative with respect to the general 5% lower bound K Ia(5%) -curve, with a 75% confidence. The use of RT NDT , instead of NDT, will generally increase the degree of conservatism, both for non-irradiated as well as irradiated materials, close to a 95% confidence level. This trend is pronounced for materials with Charpy-V upper shelf energies below 100 J. It is shown that the K IR -curve effectively constitutes a deterministic lower bound curve for crack arrest The findings are valid both for nuclear pressure vessel plates, forgings and welds

Statistical analysis of geomagnetic field intensity differences between ASM and VFM instruments onboard Swarm constellation

Science.gov (United States)

De Michelis, Paola; Tozzi, Roberta; Consolini, Giuseppe

2017-02-01

From the very first measurements made by the magnetometers onboard Swarm satellites launched by European Space Agency (ESA) in late 2013, it emerged a discrepancy between scalar and vector measurements. An accurate analysis of this phenomenon brought to build an empirical model of the disturbance, highly correlated with the Sun incidence angle, and to correct vector data accordingly. The empirical model adopted by ESA results in a significant decrease in the amplitude of the disturbance affecting VFM measurements so greatly improving the vector magnetic data quality. This study is focused on the characterization of the difference between magnetic field intensity measured by the absolute scalar magnetometer (ASM) and that reconstructed using the vector field magnetometer (VFM) installed on Swarm constellation. Applying empirical mode decomposition method, we find the intrinsic mode functions (IMFs) associated with ASM-VFM total intensity differences obtained with data both uncorrected and corrected for the disturbance correlated with the Sun incidence angle. Surprisingly, no differences are found in the nature of the IMFs embedded in the analyzed signals, being these IMFs characterized by the same dominant periodicities before and after correction. The effect of correction manifests in the decrease in the energy associated with some IMFs contributing to corrected data. Some IMFs identified by analyzing the ASM-VFM intensity discrepancy are characterized by the same dominant periodicities of those obtained by analyzing the temperature fluctuations of the VFM electronic unit. Thus, the disturbance correlated with the Sun incidence angle could be still present in the corrected magnetic data. Furthermore, the ASM-VFM total intensity difference and the VFM electronic unit temperature display a maximal shared information with a time delay that depends on local time. Taken together, these findings may help to relate the features of the observed VFM-ASM total intensity

Simulation of municipal-industrial full scale WWTP in an arid climate by application of ASM3

Directory of Open Access Journals (Sweden)

Abdelsalam Elawwad

2017-03-01

Full Text Available In developing countries, and due to the high cost of treatment of industrial wastewater, municipal wastewater treatment facilities usually receive a mixture of municipal wastewater and partially treated industrial wastewater. As a result, an increased potential for shock loads with high pollutant concentrations is expected. The use of mathematical modelling of wastewater treatment is highly efficient in such cases. A dynamic model based on activated sludge model no. 3 (ASM3 describing the performance of the activated sludge process at a full scale wastewater treatment plant (WWTP receiving mixed domestic–industrial wastewater located in an arid area is presented. ASM3 was extended by adding the Arrhenius equation to respond to changes in temperature. BioWin software V.4 was used as the model platform. The model was calibrated under steady-state conditions, adjusting only three kinetic and stoichiometric parameters: maximum heterotrophic growth rate (μH = 8 d−1, heterotrophic aerobic decay rate (bH, O2 = 0.18 d−1, and aerobic heterotrophic yield (YH,O2 = 0.4 (gCOD/gCOD. ASM3 was successful in predicting the WWTP performance, as the model was validated with 10 months of routine daily measurements. ASM3 extended with the Arrhenius equation could be helpful in the design and operation of WWTPs with mixed municipal–industrial influent in arid areas.

Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.

Science.gov (United States)

Ranganath, Prajnya; Matta, Divya; Bhavani, Gandham SriLakshmi; Wangnekar, Savita; Jain, Jamal Mohammed Nurul; Verma, Ishwar C; Kabra, Madhulika; Puri, Ratna Dua; Danda, Sumita; Gupta, Neerja; Girisha, Katta M; Sankar, Vaikom H; Patil, Siddaramappa J; Ramadevi, Akella Radha; Bhat, Meenakshi; Gowrishankar, Kalpana; Mandal, Kausik; Aggarwal, Shagun; Tamhankar, Parag Mohan; Tilak, Preetha; Phadke, Shubha R; Dalal, Ashwin

2016-10-01

Acid sphingomyelinase (ASM)-deficient Niemann-Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM-deficient NPD world-wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM-deficient NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM-deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen-2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS-MODEL workspace program. The p. (Arg542*) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM-deficient Niemann-Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparison of ASME pressure–temperature limits on the fracture probability for a pressurized water reactor pressure vessel

International Nuclear Information System (INIS)

Chou, Hsoung-Wei; Huang, Chin-Cheng

2017-01-01

Highlights: • P-T limits based on ASME K_I_a curve, K_I_C curve and RI method are presented. • Probabilistic and deterministic methods are used to evaluate P-T limits on RPV. • The feasibility of substituting P-T curves with more operational is demonstrated. • Warm-prestressing effect is critical in determining the fracture probability. - Abstract: The ASME Code Section XI-Appendix G defines the normal reactor startup (heat-up) and shut-down (cool-down) operation limits according to the fracture toughness requirement of reactor pressure vessel (RPV) materials. This paper investigates the effects of different pressure-temperature limit operations on structural integrity of a Taiwan domestic pressurized water reactor (PWR) pressure vessel. Three kinds of pressure-temperature limits based on different fracture toughness requirements – the K_I_a fracture toughness curve of ASME Section XI-Appendix G before 1998 editions, the K_I_C fracture toughness curve of ASME Section XI-Appendix G after 2001 editions, and the risk-informed revision method supplemented in ASME Section XI-Appendix G after 2013 editions, respectively, are established as the loading conditions. A series of probabilistic fracture mechanics analyses for the RPV are conducted employing ORNL’s FAVOR code considering various radiation embrittlement levels under these pressure-temperature limit conditions. It is found that the pressure-temperature operation limits which provide more operational flexibility may lead to higher fracture risks to the RPV. The cladding-induced shallow surface breaking flaws are the most critical and dominate the fracture probability of the RPV under pressure-temperature limit transients. Present study provides a risk-informed reference for the operation safety and regulation viewpoint of PWRs in Taiwan.

Interpretation, with respect to ASME code Case N-318, of limit moment and fatigue tests of lugs welded to pipe

International Nuclear Information System (INIS)

Foster, D.C.; Van Duyne, D.A.; Budlong, L.A.; Muffett, J.W.; Wais, E.A.; Streck, G.; Rodabaugh, E.C.

1990-01-01

Two nonmandatory ASME code cases have been used often in the evaluation of lugs on nuclear-power- plant piping systems. ASME Code Case N-318 provides guidance for evaluation of the design of rectangular cross-section attachments on Class 2 or 3 piping, and ASME Code Case N-122 provides guidance for evaluation of lugs on Class 1 piping. These code cases have been reviewed and evaluated based on available test data. The results indicate that the Code cases are overly conservative. Recommendations for revisions to the cases are presented which, if adopted, will reduce the overconservatism

Review of the margins for ASME code fatigue design curve - effects of surface roughness and material variability

International Nuclear Information System (INIS)

Chopra, O. K.; Shack, W. J.

2003-01-01

The ASME Boiler and Pressure Vessel Code provides rules for the construction of nuclear power plant components. The Code specifies fatigue design curves for structural materials. However, the effects of light water reactor (LWR) coolant environments are not explicitly addressed by the Code design curves. Existing fatigue strain-vs.-life ((var e psilon)-N) data illustrate potentially significant effects of LWR coolant environments on the fatigue resistance of pressure vessel and piping steels. This report provides an overview of the existing fatigue (var e psilon)-N data for carbon and low-alloy steels and wrought and cast austenitic SSs to define the effects of key material, loading, and environmental parameters on the fatigue lives of the steels. Experimental data are presented on the effects of surface roughness on the fatigue life of these steels in air and LWR environments. Statistical models are presented for estimating the fatigue (var e psilon)-N curves as a function of the material, loading, and environmental parameters. Two methods for incorporating environmental effects into the ASME Code fatigue evaluations are discussed. Data available in the literature have been reviewed to evaluate the conservatism in the existing ASME Code fatigue evaluations. A critical review of the margins for ASME Code fatigue design curves is presented

Review of the margins for ASME code fatigue design curve - effects of surface roughness and material variability.

Energy Technology Data Exchange (ETDEWEB)

Chopra, O. K.; Shack, W. J.; Energy Technology

2003-10-03

The ASME Boiler and Pressure Vessel Code provides rules for the construction of nuclear power plant components. The Code specifies fatigue design curves for structural materials. However, the effects of light water reactor (LWR) coolant environments are not explicitly addressed by the Code design curves. Existing fatigue strain-vs.-life ({var_epsilon}-N) data illustrate potentially significant effects of LWR coolant environments on the fatigue resistance of pressure vessel and piping steels. This report provides an overview of the existing fatigue {var_epsilon}-N data for carbon and low-alloy steels and wrought and cast austenitic SSs to define the effects of key material, loading, and environmental parameters on the fatigue lives of the steels. Experimental data are presented on the effects of surface roughness on the fatigue life of these steels in air and LWR environments. Statistical models are presented for estimating the fatigue {var_epsilon}-N curves as a function of the material, loading, and environmental parameters. Two methods for incorporating environmental effects into the ASME Code fatigue evaluations are discussed. Data available in the literature have been reviewed to evaluate the conservatism in the existing ASME Code fatigue evaluations. A critical review of the margins for ASME Code fatigue design curves is presented.

Flujo espiratorio máximo en niños asmáticos: Casos y controles

Directory of Open Access Journals (Sweden)

Arturo Recabarren Lozada

1995-04-01

Full Text Available Con el fin de determinar las variaciones del Flujo Espiratorio Máximo (PEF, se estudiaron a 38 niños asmáticos (CASOS en período intercrítico de la enfermedad y a 38 niños sanos (CONTROLES, de ambos sexos comprendidos entre los 5 y 15 años de edad. Los niños asmáticos fueron clasificados por parámetros clínicos en determinado grado de severidad de asma bronquial, determinando el PEF de cada niño objeto de estudio conel mini-Wright Peak Flow Meter, en 2 registros diarios a los 06 y 18 horas, durante 7 días consecutivos, obteniendo la variabilidad del mismo. Se encuentra diferencia en la variabilidad global de niños asmáticos de todos los grados de severidad de la enfermedad comprada con la de los niños normales, con diferencia estadística altamente significativa (p<0.000001. Las variaciones diurnas del PEF ayuda en el diagnóstico del asma bronquial y también son útiles para realizar la catalogación de severidad de la enfermedad. El PEF correlaciona bien con los síntomas presentados por los pacientes y por lo tanto guarda correspondencia con la Hiperreactividad bronquial (HRB del niño asmático. Postulamos que un niño con historia clínica sugestiva, una variabilidad global mayor del 8% indica que el diagnóstico de asma es altamente probable (Rev Med Hered 1995; 6: 76-82

Statistical re-evaluation of the ASME KIC and KIR fracture toughness reference curves

International Nuclear Information System (INIS)

Wallin, K.

1999-01-01

Historically the ASME reference curves have been treated as representing absolute deterministic lower bound curves of fracture toughness. In reality, this is not the case. They represent only deterministic lower bound curves to a specific set of data, which represent a certain probability range. A recently developed statistical lower bound estimation method called the 'master curve', has been proposed as a candidate for a new lower bound reference curve concept. From a regulatory point of view, the master curve is somewhat problematic in that it does not claim to be an absolute deterministic lower bound, but corresponds to a specific theoretical failure probability that can be chosen freely based on application. In order to be able to substitute the old ASME reference curves with lower bound curves based on the master curve concept, the inherent statistical nature (and confidence level) of the ASME reference curves must be revealed. In order to estimate the true inherent level of safety, represented by the reference curves, the original database was re-evaluated with statistical methods and compared to an analysis based on the master curve concept. The analysis reveals that the 5% lower bound master curve has the same inherent degree of safety as originally intended for the K IC -reference curve. Similarly, the 1% lower bound master curve corresponds to the K IR -reference curve. (orig.)

Statistical re-evaluation of the ASME KIC and KIR fracture toughness reference curves

International Nuclear Information System (INIS)

Wallin, K.; Rintamaa, R.

1998-01-01

Historically the ASME reference curves have been treated as representing absolute deterministic lower bound curves of fracture toughness. In reality, this is not the case. They represent only deterministic lower bound curves to a specific set of data, which represent a certain probability range. A recently developed statistical lower bound estimation method called the 'Master curve', has been proposed as a candidate for a new lower bound reference curve concept. From a regulatory point of view, the Master curve is somewhat problematic in that it does not claim to be an absolute deterministic lower bound, but corresponds to a specific theoretical failure probability that can be chosen freely based on application. In order to be able to substitute the old ASME reference curves with lower bound curves based on the master curve concept, the inherent statistical nature (and confidence level) of the ASME reference curves must be revealed. In order to estimate the true inherent level of safety, represented by the reference curves, the original data base was re-evaluated with statistical methods and compared to an analysis based on the master curve concept. The analysis reveals that the 5% lower bound Master curve has the same inherent degree of safety as originally intended for the K IC -reference curve. Similarly, the 1% lower bound Master curve corresponds to the K IR -reference curve. (orig.)

Summary of design of nuclear vessels and piping to ASME III (NB, NC, ND) and vessels to BS 5500

International Nuclear Information System (INIS)

Harrop, L.P.

1992-01-01

There is a hierarchy of design code requirements for pressurised components, starting with non-nuclear codes as the minimum and progressing through the ASME III nuclear Classes 3, 2, 1. In establishing and assessing the safety justifications of nuclear plants it is important to have an appreciation of the gradation of requirements in the ASME III design rules and how these go beyond non-nuclear component design rules. There are two broad aspects to the structural integrity of pressurised components, namely the achievement of integrity and the demonstration of integrity. The technical requirements of design codes are associated with achieving integrity while the documentary aspects are usually associated with demonstrating integrity. In practice documents also have a part in achieving integrity in the communication of information between different organisations and personnel involved in the design process. It is not possible to assign simple numerical measures to the relative integrity afforded by non-nuclear codes and the three Classes of ASME III. Instead it is necessary to compare the different requirements of the rules for the various technical and documentary aspects. This paper summarises the most important technical and documentary aspects of the three Classes of the ASME III Code for vessels and the non-nuclear code BS 5500. A similar summary is also provided for the three Classes of ASME III rules for piping. The intention is that the paper provides a basis for appreciating the relative integrity afforded by these various rules. (author)

Application of ASME code AG-1 to YGN 3 ampersand 4 plants, South Korea

International Nuclear Information System (INIS)

Kim, Y.K.; Porco, R.D.; York, Y.D.

1993-01-01

Yonggwang Nuclear Power Plant Units 3 ampersand 4 are located on the southwestern coast of South Korea on the Yellow Sea. The plant is owned by Korea Electric Power Corp. (KEPCO), with the engineering being performed by Korea Power Engineering Co., Inc. (KOPEC) and Sargent and Lundy under a technology transfer agreement. The plants are both 950 Megawatt (electric) pressurized water reactors of US design. Under contract to KEPCO, Korea Heavy Industries and Construction Co., Ltd. and Ellis and Watts, Division of Dynamics Corporation of America, Batavia, Ohio, supplied major components to the YGN plants in compliance to ASME AG-1. These components included safety related Air Cleaning Units, Reactor containment Fan Cooler Units, Air Handling Units, Cubicle Coolers, Duct Electric Heaters, and fans. This paper details the extent of applicability of ASME Code AG-1 to the specific equipment, description of the equipment, conformance, testing, and design required. The paper also discusses the problems encountered in implementing ASME AG-1, working around Code sections that were not complete at contract inception, conflicts in project documents and related problems. Also discussed are the logistics problems, material availability, and quality assurance aspects complicating the applications of ASME AG-1, due to the required Korean content for some components. Based on successfully supplying the equipment referenced above, it has been concluded that AG-1 is a working document and can be successfully implemented. It provides the requirements necessary for performance, design, construction, acceptance testing, and quality assurance of equipment used as components in nuclear air and gas treatment systems in nuclear facilities. The paper also addresses lessons learned and aspects of mixing US design and US built components in Korean built assemblies

Comparison of the ASME Environmental Fatigue Design Curve with the Leax' Low Bound Model

International Nuclear Information System (INIS)

Jeong, Ill Seok; Kim, Wan Jae; Jun, Hyun Ik

2010-01-01

Environmental fatigue issue long time argued between industry and regulator. The issues of the debates are about environmental fatigue data only from experiment laboratories, no evidences in fields, and over conservatism. However, NRC issued the requirement to implement it to the construction design prior to industry practical design code. American Society of Mechanical Engineers (ASME) determined to issue non-mandatory code cases of environmental fatigue design. This paper evaluated the conservatism of the ASME proposed environmental fatigue design curve in comparison with the Leax' low bound approach model of environmental fatigue curve. A group of CF8M cast austenitic stainless steel (CASS) produced in KEPCO Research Center was introduced in the evaluation

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Science.gov (United States)

2010-10-01

... Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. (a) Pressure vessels shall be designed, constructed, and inspected in accordance with section VIII of the ASME Boiler and Pressure Vessel...

Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.

Science.gov (United States)

Boulet, Louis-Philippe; Gauvreau, Gail M; Cockcroft, Donald W; Davis, Beth; Vachon, Luc; Cormier, Yvon; O'Byrne, Paul M

2015-01-01

To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma. The present study involved 24 stable, mild allergic asthmatic subjects. In a cross-over design, ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout. The effect of each treatment on the forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% decline in FEV1 (PC20), early and late asthmatic responses, and allergen-induced inflammation were measured. Seventeen subjects completed the study. During treatment with ASM-024 at 50 mg or 200 mg, the PC20 value increased respectively from a mean (± SD) 2.56±3.86 mg/mL to 4.11 mg/mL (P=0.007), and from 3.12±4.37 mg/mL to 5.23 mg/mL (P=0.005) (no change with placebo). On day 7 (day preceding allergen challenge), postdosing FEV1 increased by 2.0% with 50 mg (P=0.005) and 1.9% with 200 mg (P=0.008) (placebo -1.1%). ASM-24 had no inhibitory effect on early and late asthmatic responses, nor on sputum eosinophil or neutrophil levels. ASM-024 induced no serious adverse events, but caused cough in 22% and 48% of the subjects with 50 mg and 200 mg, respectively, compared with 10% who were on placebo. ASM-024 did not inhibit allergen-induced asthmatic response and related airway inflammation, but reduced methacholine airway responsiveness and slightly improved lung function. The mechanism by which ASM-024 improves these outcomes requires further study.

Understanding the Long-Term Spectral Variability of Cygnus X-1 from BATSE and ASM Observations

Science.gov (United States)

Zdziarski, Andrzej A.; Poutanen, Juri; Paciesas, William S.; Wen, Linqing; Six, N. Frank (Technical Monitor)

2002-01-01

We present a spectral analysis of observations of Cygnus X-1 by the RXTE/ASM (1.5-12 keV) and CGRO/BATSE (20-300 keV), including about 1200 days of simultaneous data. We find a number of correlations between intensities and hardnesses in different energy bands from 1.5 keV to 300 keV. In the hard (low) spectral state, there is a negative correlation between the ASM 1.5-12 keV flux and the hardness at any energy. In the soft (high) spectral state, the ASM flux is positively correlated with the ASM hardness (as previously reported) but uncorrelated with the BATSE hardness. In both spectral states, the BATSE hardness correlates with the flux above 100 keV, while it shows no correlation with the flux in the 20-100 keV range. At the same time, there is clear correlation between the BATSE fluxes below and above 100 keV. In the hard state, most of the variability can be explained by softening the overall spectrum with a pivot at approximately 50 keV. The observations show that there has to be another, independent variability pattern of lower amplitude where the spectral shape does not change when the luminosity changes. In the soft state, the variability is mostly caused by a variable hard (Comptonized) spectral component of a constant shape superimposed on a constant soft blackbody component. These variability patterns are in agreement with the dependence of the rms variability on the photon energy in the two states. We interpret the observed correlations in terms of theoretical Comptonization models. In the hard state, the variability appears to be driven mostly by changing flux in seed photons Comptonized in a hot thermal plasma cloud with an approximately constant power supply. In the soft state, the variability is consistent with flares of hybrid, thermal/nonthermal, plasma with variable power above a stable cold disk. Also, based on broadband pointed observations simultaneous with those of the ASM and BATSE, we find the intrinsic bolometric luminosity increases by a

High temperature structural integrity evaluation method and application studies by ASME-NH for the next generation reactor design

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Lee, Jae Han

2006-01-01

The main purpose of this paper is to establish the high temperature structural integrity evaluating procedures for the next generation reactors, which are to be operated at over 500 .deg. C and for 60 years. To do this, comparison studies of the high temperature structural design codes and assessment procedures such as the ASME-NH (USA), RCC-MR (France), DDS (Japan), and R5 (UK) are carried out in view of the accumulated inelastic strain and the creep-fatigue damage evaluations. Also the application procedures of the ASME-NH rules with the actual thermal and structural analysis results are described in detail. To overcome the complexity and the engineering costs arising from a real application of the ASME-NH rules by hand, all the procedures established in this study such as the time-dependent primary stress limits, total accumulated creep ratcheting strain limits, and the creep-fatigue damage limits are computerized and implemented into the SIE ASME-NH program. Using this program, the selected high temperature structures subjected to two cycle types are evaluated and the parametric studies for the effects of the time step size, primary load, number of cycles, normal temperature for the creep damage evaluations and the effects of the load history on the creep ratcheting strain calculations are investigated

Modification of the ASME code z-factor for circumferential surface crack in nuclear ferritic pipings

International Nuclear Information System (INIS)

Choi, Young Hwan; Chung, Yon Ki; Koh, Wan Young; Lee, Joung Bae

1996-01-01

The purpose of this paper is to modify the ASME Code Z-Factor, which is used in the evaluation of circumferential surface crack in nuclear ferritic pipings. The ASME Code Z-Factor is a load multiplier to compensate plastic load with elasto-plastic load. The current ASME Code Z-Factor underestimates pipe maximum load. In this study, the original SC. TNP method is modified first because the original SC. TNP method has a problem that the maximum allowable load predicted from the original SC. TNP method is slightly higher than that measured from the experiment. Then the new Z-Factor is developed using the modified SC. TNP method. The desirability of both the modified SC. TNP method and the new Z-Factor is examined using the experimental results for the circumferential surface crack in pipings. The results show that (1) the modified SC. TNP method is good for predicting the circumferential surface crack behavior in pipings, and (2) the Z-Factor obtained from the modified SC. TNP method well predicts the behavior of circumferential surface crack in ferritic pipings. 30 refs., 13 figs., 4 tabs. (author)

Iterative and non-iterative solutions of engine flows using ASM and k-ε turbulence models

International Nuclear Information System (INIS)

Khaleghi, H.; Fallah, E.

2003-01-01

Various turbulent models are widely developed in order to make a good prediction of turbulence phenomena in different applications. The standard k-ε model shows a poor prediction for some applications. The Reynolds Stress Model (RSM) is expected to give a better prediction of turbulent characteristics, because a separate differential equation for each Reynolds stress component is solved in this model. In order to save both time and memory in this calculation a new Algebraic Stress Model (ASM) which was developed by Lumly et al in 1995 is used for calculations of flow characteristics in the internal combustion engine chamber. With using turbulent realizability principles, this model becomes a powerful and reliable turbulence model. In this paper the abilities of the model is examined in internal combustion engine flows. The results of ASM and k-ε models are compared with the experimental data. It is shown that the poor predictions of k-ε model are modified by ASM model. Also in this paper non-iterative PISO and iterative SIMPLE solution algorithms are compared. The results show that the PISO solution algorithm is the preferred and more efficient procedure in the calculation of internal combustion engine. (author)

Adoption of ASME Code Section XI for ISI to Research Reactors

International Nuclear Information System (INIS)

Tawfik, Y.E.; El-sesy, I.A.; Shaban, H.I.; Ibrahim, M.M.

2002-01-01

ETRR-2 (Second Egyptian thermal research reactor) is a multi-purpose, pool- type reactor with an open water surface and variable core arrangement. The core power is 22 MWth, cooled and moderated by light water and with beryllium reflectors. It contains plate- type fuel elements (MTR type, 19.7% enriched uranium) with aluminum clad. The ETRR-2 reactor consist of 57 systems and around 200 subsystems. These systems contain many mechanical components such as tanks, pipes, valves, pumps, heat exchangers, cooling tower, air compressors, and supports. In this present work, a trial was made to adopt the general requirements of ASME code, section XI to ETRR-2 research reactor. ASME (American Society of Mechanical Engineers) boiler and pressure vessel Code, section XI, provides requirements for in-service inspection (ISI) and in-service testing (IST) of components and systems, and repair/replacement activities in a nuclear power plant. Also, IAEA (International Atomic Energy Authority) has published some recommendations for ISI for research reactors similar to that rules and requirements specified in ASME. The complete ISI program requires several steps that have to be performed in sequence. These steps are described in many logic flow charts (LFC's). These logic flow charts include; the general LFC's for all steps required to complete ISI program, the LFC's for examination requirements, the LFC's for flaw evaluation modules, and the LFC's for acceptability of welds for class 1 components. This program includes, also, the inspection program for welded parts of the reactor components during its lifetime. This inspection program is applied for each system and subsystem of ETRR-2 reactor. It includes the examination area type, the component type, the part to be examined, the weld type, the examination method, the inspection program schedule, and the detailed figures of the welded components. (authors)

Design and test of ASME strainer for primary cooling system in HANARO

International Nuclear Information System (INIS)

Park, Yong-Chul; Ryu, Jeong-Soo

1999-01-01

The ASME strainers have been newly installed at the suction side of each reactor coolant pump to get rid of the foreign materials which may damage the pump impeller or interfere with the coolant path of fuel flow tube or primary plate type heat exchanger. The strainer was designed in accordance with ASME SEC. III, DIV. 1, ND and the structural integrity was verified by seismic analysis. The screen was designed in accordance with the effective void area from the result of flow analysis for T-type strainer. After installation of the strainer, it was confirmed through the field test that the flow characteristics of primary cooling system were not adversely affected. The pressure loss coefficient was calculated by Darcy equation using the pressure difference through each strainer and the flow rate measured during the strainer performance test. And these are useful data to predict flow variations by the pressure difference. (author)

Comparisons of ratchetting analysis methods using RCC-M, RCC-MR and ASME codes

International Nuclear Information System (INIS)

Yang Yu; Cabrillat, M.T.

2005-01-01

The present paper compares the simplified ratcheting analysis methods used in RCC-M, RCC-MR and ASME with some examples. Firstly, comparisons of the methods in RCC-M and efficiency diagram in RCC-MR are investigated. A special method is used to describe these two methods with curves in one coordinate, and the different conservation is demonstrated. RCC-M method is also be interpreted by SR (second ratio) and v (efficiency index) which is used in RCC-MR. Hence, we can easily compare the previous two methods by defining SR as abscissa and v as ordinate and plotting two curves of them. Secondly, comparisons of the efficiency curve in RCC-MR and methods in ASME-NH APPENDIX T are investigated, with significant creep. At last, two practical evaluations are performed to show the comparisons of aforementioned methods. (authors)

When a Plant Resistance Inducer Leaves the Lab for the Field: Integrating ASM into Routine Apple Protection Practices.

Science.gov (United States)

Marolleau, Brice; Gaucher, Matthieu; Heintz, Christelle; Degrave, Alexandre; Warneys, Romain; Orain, Gilles; Lemarquand, Arnaud; Brisset, Marie-Noëlle

2017-01-01

Plant resistance inducers, also called elicitors, could be useful to reduce the use of pesticides. However, their performance in controlling diseases in the field remains unsatisfactory due to lack of specific knowledge of how they can integrate crop protection practices. In this work, we focused on apple crop and acibenzolar- S -methyl (ASM), a well-known SAR (systemic acquired resistance) inducer of numerous plant species. We provide a protocol for orchard-effective control of apple scab due to the ascomycete fungus Venturia inaequalis , by applying ASM in combination with a light integrated pest management program. Besides we pave the way for future optimization levers by demonstrating in controlled conditions (i) the high influence of apple genotypes, (ii) the ability of ASM to prime defenses in newly formed leaves, (iii) the positive effect of repeated elicitor applications, (iv) the additive effect of a thinning fruit agent.

Integrity evaluation for stud female threads on pressure vessel according to ASME code using FEM

International Nuclear Information System (INIS)

Kim, Moon Young; Chung, Nam Yong

2003-01-01

The extension of design life among power plants is increasingly becoming a world-wide trend. Kori no.1 unit in Korea is operating two cycle. It has two man-ways for tube inspection in a steam generator which is one of the important components in a nuclear power plant. Especially, stud bolts for man-way cover have damaged by disassembly and assembly several times and degradation for bolt materials for long term operation. It should be evaluated and compared by ASME code criteria for integrity evaluation. Integrity evaluation criteria which has been made by the manufacturer is not applied on the stud bolts of nuclear pressure vessels directly because it is controlled by the yield stress of ASME code. It can apply evaluation criteria through FEM analysis to damaged female threads and to evaluated safety for helical-coil method which is used according to code case-N-496-1. From analysis results, we found that it is the same results between stress intensity which got from FEM analysis on damaged female threads over 10% by manufacture integrity criteria and 2/3 yield strength criteria on ASME code. It was also confirmed that the helical-coil repair method would be safe

Parametric study of emerging high power accelerator applications using Accelerator Systems Model (ASM)

International Nuclear Information System (INIS)

Berwald, D.H.; Mendelsohn, S.S.; Myers, T.J.; Paulson, C.C.; Peacock, M.A.; Piaszczyk, CM.; Rathke, J.W.; Piechowiak, E.M.

1996-01-01

Emerging applications for high power rf linacs include fusion materials testing, generation of intense spallation neutrons for neutron physics and materials studies, production of nuclear materials and destruction of nuclear waste. Each requires the selection of an optimal configuration and operating parameters for its accelerator, rf power system and other supporting subsystems. Because of the high cost associated with these facilities, economic considerations become paramount, dictating a full evaluation of the electrical and rf performance, system reliability/availability, and capital, operating, and life cycle costs. The Accelerator Systems Model (ASM), expanded and modified by Northrop Grumman during 1993-96, provides a unique capability for detailed layout and evaluation of a wide variety of normal and superconducting accelerator and rf power configurations. This paper will discuss the current capabilities of ASM, including the available models and data base, and types of trade studies that can be performed for the above applications. (author)

Scope and implementation of standards ASME N510 / N511 in air treatment system (HVAC) of the Asco nuclear power plant; Alcance e implementacion de las normas ASME N511 en el sistema de tratamiento de aire (HVAC) de la central nuclear de Asco

Energy Technology Data Exchange (ETDEWEB)

Jaimot Jimenez, J. J.

2013-07-01

With the ITC for renewal of license units 1 and 2 of Asco, the CSN It required the commissioning tests underway in the air, according to ASME N510 filter units. It is required that, for safety-related units, to undertake preventive inspections according to ASME N511. All these requirements, in tight deadlines, have represented a great challenge for the organizations of maintenance and engineering of ANAV.

Orosomucoid-like 3 (ORMDL3) upregulates airway smooth muscle proliferation, contraction, and Ca2+ oscillations in asthma.

Science.gov (United States)

Chen, Jun; Miller, Marina; Unno, Hirotoshi; Rosenthal, Peter; Sanderson, Michael J; Broide, David H

2017-09-07

Airway hyperresponsiveness is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. We investigated whether increased ASM expression of orosomucoid-like 3 (ORMDL3), a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro and influenced airway contractility and calcium flux in ASM in precision-cut lung slices (PCLSs) from wild-type and hORMDL3 Zp3-Cre mice (which express increased levels of human ORMDL3 [hORMDL3]). Levels of ASM proliferation and contraction were assessed in ASM cells transfected with ORMDL3 in vitro. In addition, airway contractility and calcium oscillations were quantitated in ASM cells in PCLSs derived from naive wild-type and naive hORMDL3 Zp3-Cre mice, which do not have a blood supply. Increased ASM expression of ORMDL3 in vitro resulted in increased ASM proliferation and contractility. PCLSs derived from naive hORMDL3 Zp3-Cre mice, which do not have airway inflammation, exhibit increased airway contractility with increased calcium oscillations in ASM cells. Increased ASM ORMDL3 expression increases levels of ASM sarcoplasmic reticulum Ca 2+ ATPase 2b (SERCA2b), which increases ASM proliferation and contractility. Overall, these studies provide evidence that an intrinsic increase in ORMDL3 expression in ASM can induce increased ASM proliferation and contractility, which might contribute to increased airway hyperresponsiveness in the absence of airway inflammation in asthmatic patients. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Technical report on comparative analysis of ASME QA requirements and ISO series

International Nuclear Information System (INIS)

Kim, Kwan Hyun

2000-06-01

This technical report provides the differences on the QA requirement ASME and ISO in nuclear fields. This report applies to the quality assurance(QA) programmes of the design of two requirement. The organization having overall responsibility for the nuclear design, preservation, fabrication shall be described in this report in each stage of design project

Impact of ACI-ASME code on design and construction of nuclear containment structures

International Nuclear Information System (INIS)

Reedy, R.F.

1978-01-01

The effect of the ACI-ASME code for design and construction of concrete containment structures on the nuclear and concrete industries is examined. Topics covered include purpose of the code, general requirements, responsibilities and duties, design and construction specifications, quality assurance, inspection, the liner, and stamping

Enactment of KEPIC MNH Based on 2007 ASME BPVC Section III Division 1, Subsection NH: Class 1 Components in Elevated Temperature Service

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Kim, J. B.; Lee, H. Y.; Park, C. G.

2008-11-01

This report is a draft of an enactment of KEPIC MNH based on 2007 ASME Boiler and Pressure Vessel Code, Section III, Division 1 Subsection NH for Class 1 Components in Elevated Temperature Service and contains of ASME Article NH-3000 design, the mandatory appendix I-14, and non-mandatory appendices T and X

Enactment of KEPIC MNH Based on 2007 ASME BPVC Section III Division 1, Subsection NH: Class 1 Components in Elevated Temperature Service

Energy Technology Data Exchange (ETDEWEB)

Koo, Gyeong Hoi; Kim, J. B.; Lee, H. Y.; Park, C. G

2008-11-15

This report is a draft of an enactment of KEPIC MNH based on 2007 ASME Boiler and Pressure Vessel Code, Section III, Division 1 Subsection NH for Class 1 Components in Elevated Temperature Service and contains of ASME Article NH-3000 design, the mandatory appendix I-14, and non-mandatory appendices T and X.

Precipitation-hardening stainless steel bars, shapes, and forgings (ASME SA-564 with additional requirements)

International Nuclear Information System (INIS)

1975-05-01

A standard prescribing requirements for precipitation-hardening stainless steel bars, shapes, and forgings (ASME SA-564 with additional requirements) for nuclear and associated applications is presented. This standard supersedes RDT M 7-6T, dated January 1974. (U.S.)

Inelasticity and the ASME code

International Nuclear Information System (INIS)

Berman, I.

1978-01-01

Although it may have more general applicability, this paper is specifically concerned with some aspects of plasticity for class I nuclear components that are contained in section III of the ASME Boiler and Pressure Vessel Code. It directly addresses design for components at temperatures at which creep is not a factor. A review is made of the relationship of plasticity to each of the three failure modes that the stress limits are intended to prevent. It is found that the prevention of bursting and gross distortion from a single application of pressure and the prevention of fatigue failure caused by repeated cycles of peak stresses are well supported by experimental results. The experimental verification for the rules to show that the primary plus secondary stresses shakedown to elastic behavior is not clear. Various directed efforts which could lead to greater assurance of shakedown to elastic behavior are suggested. The major approach should be a massive program to develop a test matrix of experimental information for various portions of each component of interest in the Code. (Auth.)

The Human Cell Atlas.

Science.gov (United States)

Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

2017-12-05

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

Comparison of ASME Code NB-3200 and NB-3600 results for fatigue analysis of B31.1 branch nozzles

International Nuclear Information System (INIS)

Nitzel, M.E.; Ware, A.G.; Morton, D.K.

1996-01-01

Fatigue analyses wre conducted on two reactor coolant system branch nozzles in an operating PWR designed to the B31.1 Code, for which no explicit fatigue analysis was required by the licensing basis. These analyses were performed as part of resolving issues connected with NRC's Fatigue Action Plan to determine if the cumulative usage factor (CUF) for these nozzles, using the 1992 ASME Code and representative PWR transients, were comparable to nozzles designed and analyzed to the ASME Code. Both NB-3200 and NB-3600 ASME Code methods were used. NB-3200 analyses included the development of finite element models for each nozzle. Although detailed thermal transients were not available for the plant analyzed, representative transients from similar PWRs were applied in each method. CUFs calculated using NB-3200 methods were significantly less than using NB-3600. The paper points out differences in analysis methods and highlights difficulties and unknowns in performing more detailed analyses to reduce conservative assumptions

Development and application of proposed ASME Section XI Code changes for risk-based inspection of piping

International Nuclear Information System (INIS)

West, R.A.

1996-01-01

This synopsis has been written to describe a perspective on the development and application of ASME Section XI Code changes for risk-based inspection of piping. The content is specifically related to the use of risk-based technology for Inservice Inspection (ISI) of piping and efforts made to support the ASME Research/Westinghouse Owners Group/Millstone Unit 3 approach for use of this technology. The opinions contained herein may or may not reflect those of the ASME Codes and Standards Committees responsible for these activities. In order to take such a detailed technical subject and put it into an understandable format, the author has chosen to provide an analogy to simplify what is actually taking place. Risk-based technology in the ISI of piping can be likened to the process of making and using specifically ground prescription glasses to allow for better vision. It provides a process to develop and use these uniquely ground glasses that will dynamically focus on all the locations and obstacles within a plant's piping systems that could cause that plant to trip and fall; more importantly it identifies the locations where the fall could possibly hurt someone else. In this way, Nuclear Safety is being addressed

Elastic-plastic stress analysis and ASME code evaluation of a bottomhead penetration in a reactor pressure vessel

International Nuclear Information System (INIS)

Ranganath, S.

1979-01-01

Nuclear pressure vessel components are designed to meet the requirements of Section III of the ASME Boiler and Pressure Vessel Code. Specifically, the design must satisfy the limits on stress range and fatigue usage prescribed in NB-3200, Section III ASME Code for the various design and operating conditions for the component. The Code requirements assure that the component does not experience gross yielding and that in general, elastic shakedown occurs following cyclic loading. When elastic stress analysis is performed this can be shown by meeting the limits in the Code on Primary and Primary plus Secondary (P+Q) stress intensities. However, when the P+Q limits cannot be met and elastic Shakedown cannot be demonstrated, plastic analysis may be performed to meet the requirements of the Code. This paper describes the elastic-plastic stress analysis of a Boiling Water Reactor Vessel bottom head in-core penetration and illustrates how plastic analysis can be used in ASME Code evaluations to show Code compliance. Details of the thermal analysis, elastic-plastic stress analysis and fatigue evaluation are presented and it is shown that the in-core penetration satisfies the code requirements. 6 refs

ASTM and ASME-BPE Standards--Complying with the Needs of the Pharmaceutical Industry.

Science.gov (United States)

Huitt, William M

2011-01-01

Designing and building a pharmaceutical facility requires the owner, engineer of record, and constructor to be knowledgeable with regard to the industry codes and standards that apply to this effort. Up until 1997 there were no industry standards directed at the needs and requirements of the pharmaceutical industry. Prior to that time it was a patchwork effort at resourcing and adopting nonpharmaceutical-related codes and standards and then modifying them in order to meet the more stringent requirements of the Food and Drug Administration (FDA). In 1997 the American Society of Mechanical Engineers (ASME) published the first Bioprocessing Equipment (BPE) Standard. Through harmonization efforts this relatively new standard has brought together, scrutinized, and refined industry accepted methodologies together with FDA compliance requirements, and has established an American National Standard that provides a comprehensive set of standards that are integral to the pharmaceutical industry. This article describes various American National Standards, including those developed and published by the American Society for Testing and Materials (ASTM), and how they apply to the pharmaceutical industry. It goes on to discuss the harmonization effort that takes place between the various standards developers in an attempt to prevent conflicts and omissions between the many standards. Also included are examples of tables and figures taken from the ASME-BPE Standard. These examples provide the reader with insight to the relevant content of the ASME-BPE Standard. Designing and building a pharmaceutical facility requires the owner, engineer of record, and constructor to be knowledgeable with regard to the industry codes and standards that apply to this effort. Up until 1997 there were no industry standards directed at the needs and requirements of the pharmaceutical industry. Prior to that time it was a patchwork effort at resourcing and adopting nonpharmaceutical-related codes and

Elastic creep-fatigue evaluation for ASME code

International Nuclear Information System (INIS)

Severud, L.K.; Winkel, B.V.

1987-01-01

Experience with applying the ASME Code Case N-47 rules for evaluation of creep-fatigue with elastic analysis results has been problematic. The new elastic evaluation methods are intended to bound the stress level and strain range values needed for use in employing the code inelastic analysis creep-fatigue damage counting procedures. To account for elastic followup effects, ad hoc rules for stress classification, shakedown, and ratcheting are employed. Because elastic followup, inelastic strain concentration, and stress-time effects are accounted for, the design fatigue curves in Case N-47 for inelastic analysis are used instead of the more conservative elastic analysis curves. Creep damage assessments are made using an envelope stress-time history that treats multiple load events and repeated cycles during elevated temperature service life. (orig./GL)

The human cell atlas

DEFF Research Database (Denmark)

Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.

2017-01-01

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

Prediction of surface cracks from thick-walled pressurized vessels with ASME code

International Nuclear Information System (INIS)

Thieme, W.

1983-01-01

The ASME-Code, Section XI, Appendix A 'Analysis of flow indications' is still non-mandatory for the pressure components of nuclear power plants. It is certainly difficult to take realistic account of the many factors influencing crack propagation while making life predictions. The accuracy of the US guideline is analysed, and its possible applications are roughly outlined. (orig./IHOE) [de

The statistical background to proposed ASME/MPC fracture toughness reference curves

International Nuclear Information System (INIS)

Oldfield, W.

1981-01-01

The ASME Pressure Vessel Codes define, in Sec. 11, lower bound fracture toughness curves. These curves are used to predict the lower bound fracture toughness on the basis of the RT test procedure. This test is used to remove heat to heat differences, by permitting the lower bound (reference) curve to be moved along the temperature scale according to the measured RT. Numerous objections have been raised to the procedure, and a Subcommittee (the ASME/MPC Working Group on Reference Toughness) is currently revising the codified procedures for fracture toughness prediction. The task has required a substantial amount of statistical work, since the new procedure are to have a statistical basis. Using initiation fracture toughness (J-Integral R curve procedures in the ductile domain) it was shown that when CVN energy data is properly transformed it is highly correlated with valid fracture toughness measurements. A single functional relationship can be used to predict the mean fracture toughness for a sample of steel from a set of CVN energy measurements, and the coefficients of the function tabulated. More importantly, the approximate lower statistical bounds to the initiation fracture toughness behaviour can be similarly predicted, and coefficients for selected bounds have also been tabulated. (orig.)

Development of ASME Code Section 11 visual examination requirements

International Nuclear Information System (INIS)

Cook, J.F.

1990-01-01

Section XI of the American Society for Mechanical Engineers Boiler and Pressure Vessel Code (ASME Code) defines three types of nondestructive examinations, visual, surface, and volumetric. Visual examination is important since it is the primary examination method for many safety-related components and systems and is also used as a backup examination for the components and systems which receive surface or volumetric examinations. Recent activity in the Section XI Code organization to improve the rules for visual examinations is reviewed and the technical basis for the new rules, which cover illumination, vision acuity, and performance demonstration, is explained

Working together for the common good: cell-cell communication in bacteria.

Science.gov (United States)

Stevens, Ann M; Schuster, Martin; Rumbaugh, Kendra P

2012-05-01

The 4th ASM Conference on Cell-Cell Communication in Bacteria was held in Miami, FL, from 6 to 9 November 2011. This review highlights three key themes that emerged from the many exciting talks and poster presentations in the area of quorum sensing: sociomicrobiology, signal transduction mechanisms, and interspecies communication.

The ASM-NSF Biology Scholars Program: An Evidence-Based Model for Faculty Development

Directory of Open Access Journals (Sweden)

Amy L. Chang

2016-05-01

Full Text Available The American Society for Microbiology (ASM established its ASM-NSF (National Science Foundation Biology Scholars Program (BSP to promote undergraduate education reform by 1 supporting biologists to implement evidence-based teaching practices, 2 engaging life science professional societies to facilitate biologists’ leadership in scholarly teaching within the discipline, and 3 participating in a teaching community that fosters disciplinary-level science, technology, engineering, and mathematics (STEM reform. Since 2005, the program has utilized year-long residency training to provide a continuum of learning and practice centered on principles from the scholarship of teaching and learning (SoTL to more than 270 participants (“scholars” from biology and multiple other disciplines. Additionally, the program has recruited 11 life science professional societies to support faculty development in SoTL and discipline-based education research (DBER. To identify the BSP’s long-term outcomes and impacts, ASM engaged an external evaluator to conduct a study of the program’s 2010­–2014 scholars (n = 127 and society partners. The study methods included online surveys, focus groups, participant observation, and analysis of various documents. Study participants indicate that the program achieved its proposed goals relative to scholarship, professional society impact, leadership, community, and faculty professional development. Although participants also identified barriers that hindered elements of their BSP participation, findings suggest that the program was essential to their development as faculty and provides evidence of the BSP as a model for other societies seeking to advance undergraduate science education reform. The BSP is the longest-standing faculty development program sponsored by a collective group of life science societies. This collaboration promotes success across a fragmented system of more than 80 societies representing the life

The ASM-NSF Biology Scholars Program: An Evidence-Based Model for Faculty Development.

Science.gov (United States)

Chang, Amy L; Pribbenow, Christine M

2016-05-01

The American Society for Microbiology (ASM) established its ASM-NSF (National Science Foundation) Biology Scholars Program (BSP) to promote undergraduate education reform by 1) supporting biologists to implement evidence-based teaching practices, 2) engaging life science professional societies to facilitate biologists' leadership in scholarly teaching within the discipline, and 3) participating in a teaching community that fosters disciplinary-level science, technology, engineering, and mathematics (STEM) reform. Since 2005, the program has utilized year-long residency training to provide a continuum of learning and practice centered on principles from the scholarship of teaching and learning (SoTL) to more than 270 participants ("scholars") from biology and multiple other disciplines. Additionally, the program has recruited 11 life science professional societies to support faculty development in SoTL and discipline-based education research (DBER). To identify the BSP's long-term outcomes and impacts, ASM engaged an external evaluator to conduct a study of the program's 2010-2014 scholars (n = 127) and society partners. The study methods included online surveys, focus groups, participant observation, and analysis of various documents. Study participants indicate that the program achieved its proposed goals relative to scholarship, professional society impact, leadership, community, and faculty professional development. Although participants also identified barriers that hindered elements of their BSP participation, findings suggest that the program was essential to their development as faculty and provides evidence of the BSP as a model for other societies seeking to advance undergraduate science education reform. The BSP is the longest-standing faculty development program sponsored by a collective group of life science societies. This collaboration promotes success across a fragmented system of more than 80 societies representing the life sciences and helps

Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.

Science.gov (United States)

Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Beers, Jeanette; Chen, Guokai; Soheilian, Ferri; Baxa, Ulrich; Wang, Mengqiao; Marugan, Juan J; Muro, Silvia; Li, Zhiyuan; Brady, Roscoe; Zheng, Wei

2016-12-01

: Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, δ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development. Currently, there is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were generated from patient dermal fibroblasts and differentiated into neural stem cells. By using the differentiated NPA neuronal cells as a cell-based disease model system, α-tocopherol, δ-tocopherol, and hydroxypropyl-β-cyclodextrin significantly reduced sphingomyelin accumulation in these NPA neuronal cells. Therefore, this cell-based NPA model can be used for further study of

Comparative studies on the effects of a yucca extract and acibenzolar-S-methyl (ASM) on inhibition of Venturia inaequalis in apple leaves

DEFF Research Database (Denmark)

Bengtsson, Marianne Vibeke; Wulff, Ednar Gadelha; Jørgensen, Hans Jørgen Lyngs

2009-01-01

The effect of an extract of Yucca schidigera on the control and infection process of the apple scab pathogen, Venturia inaequalis, was examined and compared with the chemical resistance inducer, acibenzolar-S-methyl (ASM). In seedling assays, both materials significantly reduced apple scab symptoms...... and pathogen sporulation on leaves and both showed similar control efficacies as the reference treatment, sulphur. Whereas yucca extract and sulphur gave significant inhibition of conidial germination in vitro, ASM did not inhibit germination. Histopathological studies of the infection process of V. inaequalis...... in apple leaves showed that the yucca extract primarily acted by inhibiting pre-penetration events and penetration itself. In contrast, the ASM treatment significantly inhibited more stages of the infection process (pre-penetration, penetration and post-penetration events). These observations suggest...

Alteraciones espirométricas en pacientes asmáticos del municipio Majibacoa, 2009-2013

Directory of Open Access Journals (Sweden)

Mailin Molina Leyva

2014-08-01

Full Text Available Se realizó un estudio descriptivo, con el objetivo de identificar alteraciones espirométricas en pacientes asmáticos del municipio Majibacoa, en el período comprendido desde enero del 2009 a enero del 2013. La muestra se integró por cincuenta pacientes asmáticos con más de 20 años de evolución de la enfermedad. Se les realizó previo consentimiento informado y una prueba espirométrica. Predominó el sexo femenino y las edades comprendidas entre 35 y 54 años. Prevalecieron los pacientes en la categoría de asma persistente severa. El volumen espiratorio forzado del primer segundo se comportó patológico en el mayor por ciento de los pacientes y la capacidad vital forzada mostró alteración en un menor número de pacientes. El patrón espirométrico obstructivo fue el más frecuente en los pacientes estudiados

Long periodicity of Blazar with RXTE ASM, TA and HEGRA

OpenAIRE

Osone, S.; Teshima, M.

2002-01-01

Long periodicity for Mkn501 during a large flare in 1997 have been reported by TA, HEGRA group. Here, we establish this periodicity with archival data of RXTE All Sky Monitor(ASM), Telescope Array(TA) and HEGRA with a chance probability less than $10^{-5}$. We also find that an origin of 23 day periodicity is related with a change of either a gamma factor of electrons $\\gamma$ or the magnetic field or a beaming factor. And, in order to search for a category which have a long periodicity, we m...

Comparison of Fatigue crack growth rate of Type 347 stainless steel with ASME and JSME models

Energy Technology Data Exchange (ETDEWEB)

Hong, Seokmin; Min, Ki-Deuk; Jeon, Soon-Hyeok; Lee, Bong-Sang [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

In this study, the FCGR of 347SS was evaluated in modified PWR high temperature water conditions. The FCGRs of 347SS under modified pressurized-water conditions were measured by using compact-tension (CT) specimens at different levels of dissolved oxygen (DO), and it were compared with other models proposed by ASME and Japanese groups. Corrosion fatigue is main factor of environmental fatigue effect. Increase of DO level in water induced more corrosion damage, and it accelerated FCGR in PWR and FCGR of 347SS in PWR water condition was faster than reference curves in J-PWR and ASME draft code case derived by 304 and 316 stainless steel, but it was slower than J-BWR reference curve. Using J-BWR model for estimating the FCGR of 347SS under PWR might be conservative.

Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

Science.gov (United States)

Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

2006-01-01

Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

Regulatory Safety Issues in the Structural Design Criteria of ASME Section III Subsection NH and for Very High Temperatures for VHTR & GEN IV

Energy Technology Data Exchange (ETDEWEB)

William J. O’Donnell; Donald S. Griffin

2007-05-07

The objective of this task is to identify issues relevant to ASME Section III, Subsection NH [1], and related Code Cases that must be resolved for licensing purposes for VHTGRs (Very High Temperature Gas Reactor concepts such as those of PBMR, Areva, and GA); and to identify the material models, design criteria, and analysis methods that need to be added to the ASME Code to cover the unresolved safety issues. Subsection NH was originally developed to provide structural design criteria and limits for elevated-temperature design of Liquid Metal Fast Breeder Reactor (LMFBR) systems and some gas-cooled systems. The U.S. Nuclear Regulatory Commission (NRC) and its Advisory Committee for Reactor Safeguards (ACRS) reviewed the design limits and procedures in the process of reviewing the Clinch River Breeder Reactor (CRBR) for a construction permit in the late 1970s and early 1980s, and identified issues that needed resolution. In the years since then, the NRC and various contractors have evaluated the applicability of the ASME Code and Code Cases to high-temperature reactor designs such as the VHTGRs, and identified issues that need to be resolved to provide a regulatory basis for licensing. This Report describes: (1) NRC and ACRS safety concerns raised during the licensing process of CRBR , (2) how some of these issues are addressed by the current Subsection NH of the ASME Code; and (3) the material models, design criteria, and analysis methods that need to be added to the ASME Code and Code Cases to cover unresolved regulatory issues for very high temperature service.

Elastic creep-fatigue evaluation for ASME [American Society of Mechanical Engineers] code

International Nuclear Information System (INIS)

Severud, L.K.; Winkel, B.V.

1987-02-01

Reassessment of past ASME N-47 creep-fatigue rules have been under way by committee members. The new proposed elastic creep-fatigue methods are easier to apply than those previously in the code case. They also provide a wider range of practical application while still providing conservative assessments. It is expected that new N-47 code rules for elastic creep-fatigue evaluation will be adopted in the near future

Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis.

Science.gov (United States)

Taniguchi, M; Ogiso, H; Takeuchi, T; Kitatani, K; Umehara, H; Okazaki, T

2015-04-09

We previously reported that IL-2 deprivation induced acid sphingomyelinase-mediated (ASM-mediated) ceramide elevation and apoptosis in an NK/T lymphoma cell line KHYG-1. However, the molecular mechanism of ASM-ceramide-mediated apoptosis during IL-2 deprivation is poorly understood. Here, we showed that IL-2 deprivation induces caspase-dependent apoptosis characterized by phosphatidylserine externalization, caspase-8, -9, and -3 cleavage, and degradation of X-linked inhibitor of apoptosis protein (XIAP). IL-2 re-supplementation rescued apoptosis via inhibition of XIAP degradation without affecting caspase cleavage. However, IL-2 deprivation induced ceramide elevation via ASM in lysosomes and activated lysosomal cathepsin B (CTSB) but not cathepsin D. A CTSB inhibitor CA-074 Me and knockdown of CTSB inhibited ceramide-mediated XIAP degradation and apoptosis. Inhibition of ceramide accumulation in lysosomes using an ASM inhibitor, desipramine, decreased cytosolic activation of CTSB by inhibiting its transfer into cytosol from the lysosome. Knockdown of ASM also inhibited XIAP degradation and apoptosis. Furthermore, cell permeable N-acetyl sphingosine (C2-ceramide), which increases mainly endogenous d18:1/16:0 and d18:1/24:1 ceramide-like IL-2 deprivation, induced caspase-dependent apoptosis with XIAP degradation through CTSB. These findings suggest that lysosomal ceramide produced by ASM mediates XIAP degradation by activation of cytosolic CTSB and caspase-dependent apoptosis. The ASM-ceramide-CTSB signaling axis is a novel pathway of ceramide-mediated apoptosis in IL-2-deprived NK/T lymphoma cells.

Comparative study of design of piping supports class 1, 2 and 3 considering german code KTA and ASME III - NF

International Nuclear Information System (INIS)

Faloppa, Altair A.; Fainer, Gerson; Mattar Neto, Miguel; Elias, Marcos V.

2013-01-01

The objective of this paper is developing a comparative study of the design criteria for class 1, 2, 3 piping supports considering the American Code ASME Section III - NF and the German Code KTA 3205.1 to the Primary Circuit, KTA 3205.2 to the others systems and KTA 3205.3 series-production standards supports of a PWR nuclear power plant. An additional purpose of the paper is a general analysis of the main design concepts of the American Code ASME Boiler and Pressure Vessel Code, Section III, Division 1 and German Nuclear Design Code KTA that was performed in order to aid the comparative study proposed. The relevance of this study is to show the differences between codes ASME and KTA since they were applied in the design of the Nuclear Power Plants Angra 1 and Angra 2, and to the design of Angra 3, which is at the moment under construction. It is also considered their use in the design of nuclear installations such as RMB - Reator MultiProposito Brasileiro and LABGENE - Laboratorio de Geracao Nucleoeletrica. (author)

Statistical re-evaluation of the ASME K{sub IC} and K{sub IR} fracture toughness reference curves

Energy Technology Data Exchange (ETDEWEB)

Wallin, K.; Rintamaa, R. [Valtion Teknillinen Tutkimuskeskus, Espoo (Finland)

1998-11-01

Historically the ASME reference curves have been treated as representing absolute deterministic lower bound curves of fracture toughness. In reality, this is not the case. They represent only deterministic lower bound curves to a specific set of data, which represent a certain probability range. A recently developed statistical lower bound estimation method called the `Master curve`, has been proposed as a candidate for a new lower bound reference curve concept. From a regulatory point of view, the Master curve is somewhat problematic in that it does not claim to be an absolute deterministic lower bound, but corresponds to a specific theoretical failure probability that can be chosen freely based on application. In order to be able to substitute the old ASME reference curves with lower bound curves based on the master curve concept, the inherent statistical nature (and confidence level) of the ASME reference curves must be revealed. In order to estimate the true inherent level of safety, represented by the reference curves, the original data base was re-evaluated with statistical methods and compared to an analysis based on the master curve concept. The analysis reveals that the 5% lower bound Master curve has the same inherent degree of safety as originally intended for the K{sub IC}-reference curve. Similarly, the 1% lower bound Master curve corresponds to the K{sub IR}-reference curve. (orig.)

Towards a consensus-based biokinetic model for green microalgae - The ASM-A.

Science.gov (United States)

Wágner, Dorottya S; Valverde-Pérez, Borja; Sæbø, Mariann; Bregua de la Sotilla, Marta; Van Wagenen, Jonathan; Smets, Barth F; Plósz, Benedek Gy

2016-10-15

Cultivation of microalgae in open ponds and closed photobioreactors (PBRs) using wastewater resources offers an opportunity for biochemical nutrient recovery. Effective reactor system design and process control of PBRs requires process models. Several models with different complexities have been developed to predict microalgal growth. However, none of these models can effectively describe all the relevant processes when microalgal growth is coupled with nutrient removal and recovery from wastewaters. Here, we present a mathematical model developed to simulate green microalgal growth (ASM-A) using the systematic approach of the activated sludge modelling (ASM) framework. The process model - identified based on a literature review and using new experimental data - accounts for factors influencing photoautotrophic and heterotrophic microalgal growth, nutrient uptake and storage (i.e. Droop model) and decay of microalgae. Model parameters were estimated using laboratory-scale batch and sequenced batch experiments using the novel Latin Hypercube Sampling based Simplex (LHSS) method. The model was evaluated using independent data obtained in a 24-L PBR operated in sequenced batch mode. Identifiability of the model was assessed. The model can effectively describe microalgal biomass growth, ammonia and phosphate concentrations as well as the phosphorus storage using a set of average parameter values estimated with the experimental data. A statistical analysis of simulation and measured data suggests that culture history and substrate availability can introduce significant variability on parameter values for predicting the reaction rates for bulk nitrate and the intracellularly stored nitrogen state-variables, thereby requiring scenario specific model calibration. ASM-A was identified using standard cultivation medium and it can provide a platform for extensions accounting for factors influencing algal growth and nutrient storage using wastewater resources. Copyright �

Assessment of ASME code examinations on regenerative, letdown and residual heat removal heat exchangers

International Nuclear Information System (INIS)

Gosselin, Stephen R.; Cumblidge, Stephen E.; Anderson, Michael T.; Simonen, Fredric A.; Tinsley, G A.; Lydell, B.; Doctor, Steven R.

2005-01-01

Inservice inspection requirements for pressure retaining welds in the regenerative, letdown, and residual heat removal heat exchangers are prescribed in Section XI Articles IWB and IWC of the ASME Boiler and Pressure Vessel Code. Accordingly, volumetric and/or surface examinations are performed on heat exchanger shell, head, nozzle-to-head, and nozzle-to-shell welds. Inspection difficulties associated with the implementation of these Code-required examinations have forced operating nuclear power plants to seek relief from the U.S. Nuclear Regulatory Commission. The nature of these relief requests are generally concerned with metallurgical, geometry, accessibility, and radiation burden. Over 60% of licensee requests to the NRC identify significant radiation exposure burden as the principle reason for relief from the ASME Code examinations on regenerative heat exchangers. For the residual heat removal heat exchangers, 90% of the relief requests are associated with geometry and accessibility concerns. Pacific Northwest National Laboratory was funded by the NRC Office of Nuclear Regulatory Research to review current practice with regard to volumetric and/or surface examinations of shell welds of letdown heat exchangers regenerative heat exchangers and residual (decay) heat removal heat exchangers Design, operating, common preventative maintenance practices, and potential degradation mechanisms are reviewed. A detailed survey of domestic and international PWR-specific operating experience was performed to identify pressure boundary failures (or lack of failures) in each heat exchanger type and NSSS design. The service data survey was based on the PIPExp- database and covers PWR plants worldwide for the period 1970-2004. Finally a risk assessment of the current ASME Code inspection requirements for residual heat removal, letdown, and regenerative heat exchangers is performed. The results are then reviewed to discuss the examinations relative to plant safety and

Defective repair of UV-damaged DNA in human tumor and SV40-transformed human cells but not in adenovirus-transformed human cells

International Nuclear Information System (INIS)

Rainbow, A.J.

1989-01-01

The DNA repair capacities of five human tumor cell lines, one SV40-transformed human cell line and one adenovirus-transformed human cell line were compared with that of normal human fibroblasts using a sensitive host cell reactivation (HCR) technique. Unirradiated and UV-irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens (Vag) in the various cell types using immunofluorescent staining. The survival of Vag formation for UV-irradiated Ad 2 was significantly reduced in all the human tumor cell lines and the SV40-transformed human line compared to the normal human fibroblasts, but was apparently normal in the adenovirus-transformed human cells. D 0 values for the UV survival of Ad 2 Vag synthesis in the tumor and virally transformed lines expressed as a percentage of that obtained on normal fibroblast strains were used as a measure of DNA repair capacity. Percent HCR values ranged from 26 to 53% in the tumor cells. These results indicate a deficiency in the repair of UV-induced DNA damage associated with human tumorigenesis and the transformation of human cells by SV40 but not the transformation of human cells by adenovirus. (author)

Efecto de budesonida sobre la densidad y el metabolismo óseo en niños asmáticos

Directory of Open Access Journals (Sweden)

Paoli de Valeri Mariela

2000-01-01

Full Text Available OBJETIVO: Determinar el efecto de la administración de budesonida inhalado sobre la densidad, el contenido mineral y el metabolismo óseo en niños asmáticos. MATERIAL Y MÉTODOS: Estudio transversal realizado de septiembre de 1996 a julio de 1997, en el que se estudiaron 38 niños y niñas de entre 6 y 11 años de edad, seleccionados de la consulta externa de neumonología infantil del Instituto Autónomo Hospital Universitario de Los Andes, Mérida, Venezuela. Se constituyeron tres grupos: nueve niños asmáticos tratados con budesonida inhalado (300 µg/día en promedio durante más de seis meses, (grupo A, 14 niños asmáticos que no recibieron tratamiento esteroideo (grupo B y 15 niños no asmáticos (grupo C. A todos se les practicó una evaluación ósea con marcadores de formación y resorción y con una medición de la densidad (DMO y el contenido mineral óseo (CMO. Se calcularon medidas de tendencia central y de dispersión, se realizó análisis de varianza, y se utilizaron las pruebas de Fisher y Scheffé para comparación de medias. RESULTADOS: En los grupos estudiados (A, B y C los niveles séricos de calcio fueron 9.1±0.3; 9.6±0.4; 9.3±0.6 mg/ml; los de osteocalcina fueron 14.8±4.6; 13.0±2.5; 11.9±3.4 ng/dl; los de telopéptido carboxiterminal del colágeno tipo I (ICTP fueron 19.6±16.5; 14.2±15.4; 13.0±18.3 µg/l; la DMO fue de 0.67±0.06; 0.68±0.06; 0.69±0.06 g/cm², y el CMO fue de 1 158.8±217.4; 1 106.4±256.1; 1 176.5±240.5 g, respectivamente. No hubo diferencias significativas entre los grupos. CONCLUSIONES: La administración de budesonida inhalada en dosis de 100 a 400 µg/día por un periodo de seis meses no produce modificaciones en la densidad y en el metabolismo óseo en niños asmáticos.

Regulatory Safety Issues in the Structural Design Criteria of ASME Section III Subsection NH and for Very High Temperatures for VHTR and GEN IV

International Nuclear Information System (INIS)

O'Donnell, William J.; Griffin, Donald S.

2007-01-01

The objective of this task is to identify issues relevant to ASME Section III, Subsection NH [1], and related Code Cases that must be resolved for licensing purposes for VHTGRs (Very High Temperature Gas Reactor concepts such as those of PBMR, Areva, and GA); and to identify the material models, design criteria, and analysis methods that need to be added to the ASME Code to cover the unresolved safety issues. Subsection NH was originally developed to provide structural design criteria and limits for elevated-temperature design of Liquid Metal Fast Breeder Reactor (LMFBR) systems and some gas-cooled systems. The U.S. Nuclear Regulatory Commission (NRC) and its Advisory Committee for Reactor Safeguards (ACRS) reviewed the design limits and procedures in the process of reviewing the Clinch River Breeder Reactor (CRBR) for a construction permit in the late 1970s and early 1980s, and identified issues that needed resolution. In the years since then, the NRC and various contractors have evaluated the applicability of the ASME Code and Code Cases to high-temperature reactor designs such as the VHTGRs, and identified issues that need to be resolved to provide a regulatory basis for licensing. This Report describes: (1) NRC and ACRS safety concerns raised during the licensing process of CRBR , (2) how some of these issues are addressed by the current Subsection NH of the ASME Code; and (3) the material models, design criteria, and analysis methods that need to be added to the ASME Code and Code Cases to cover unresolved regulatory issues for very high temperature service.

Genome engineering in human cells.

Science.gov (United States)

Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

2014-01-01

Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

Comportamiento de variables clínico-epidemiológicas en pacientes asmáticos. Consultorio Médico de Familia 14, Puerto Padre

Directory of Open Access Journals (Sweden)

José Ramón Martínez Pérez

2015-12-01

Full Text Available Se realizó un estudio descriptivo de corte transversal en 40 pacientes asmáticos de todas las edades, pertenecientes al Consultorio 14 del área de salud de Puerto Padre, provincia de Las Tunas, durante los meses de enero a junio de 2008; con el objetivo de determinar el comportamiento de variables clínico-epidemiológicas en dichos pacientes. Para cumplimentar los objetivos se diseñó una encuesta que recogió las variables de interés. El análisis se hizo a través del sistema Statistix, permitiendo  obtener  la distribución de frecuencia y los porcientos. El test de Chi-Cuadrado se empleó en la comparación de variables cualitativas. Los resultados fueron descritos, interpretados y comparados con otros estudios. Se concluye que los pacientes grado I según Kraeppelin son los mas representados en nuestra población de pacientes asmáticos;  los broncodilatadores son los medicamentos mas utilizados por la población asmática estudiada; el incumplimiento del tratamiento medicamentoso no se relacionó con la severidad de la enfermedad en la población estudiada;  las malas condiciones de la vivienda y  el tabaquismo influyeron de forma negativa en la evolución del paciente asmático.

Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

NARCIS (Netherlands)

Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

2008-01-01

Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

Analysis of the ASME methodology for evaluation of erosion-corrosion defects with respect to the differences in the calculation and in materials used at the Dukovany NPP

International Nuclear Information System (INIS)

Kadecka, P.

1995-01-01

The problem of evaluation of tolerable defects and thinning of pipe walls was analyzed. In fact, a procedure for evaluation of tolerable defects is described in ASME Code Case N 480 based on the ASME ''Rules for Construction of Nuclear Power Plant Components''. The pipe systems of the Dukovany NPP, however, were constructed to different (East European) standards, and therefore caution should be exercised when applying US standards to this plant. The report demonstrates major differences between the ASME Standard and the proposed Czech standard ''A.S.I. Standards Documentation for Strength Calculations of Equipment and Piping of WWER Type Nuclear Power Plants'' developed by the Czech Association of Mechanical Engineers (A.S.I), evaluates the applicability of Code Case N 480 to the Dukovany plant, and proposes a Czech procedure for the evaluation. The basic characteristics of materials cited by ASME II and carbon steels used in the secondary circuit of the Dukovany NPP are also compared. (P.A.). 78 tabs., 2 figs., 4 refs

FY16 ASME High Temperature Code Activities

Energy Technology Data Exchange (ETDEWEB)

Swindeman, M. J. [Chromtech Inc., Oak Ridge, TN (United States); Jetter, R. I. [R. I Jetter Consulting, Pebble Beach, CA (United States); Sham, T. -L. [Argonne National Lab. (ANL), Argonne, IL (United States)

2016-09-01

One of the objectives of the ASME high temperature Code activities is to develop and validate both improvements and the basic features of Section III, Division 5, Subsection HB, Subpart B (HBB). The overall scope of this task is to develop a computer program to be used to assess whether or not a specific component under specified loading conditions will satisfy the elevated temperature design requirements for Class A components in Section III, Division 5, Subsection HB, Subpart B (HBB). There are many features and alternative paths of varying complexity in HBB. The initial focus of this task is a basic path through the various options for a single reference material, 316H stainless steel. However, the program will be structured for eventual incorporation all the features and permitted materials of HBB. Since this task has recently been initiated, this report focuses on the description of the initial path forward and an overall description of the approach to computer program development.

Draft ASME code case on ductile cast iron for transport packaging

International Nuclear Information System (INIS)

Saegusa, T.; Arai, T.; Hirose, M.; Kobayashi, T.; Tezuka, Y.; Urabe, N.; Hueggenberg, R.

2004-01-01

The current Rules for Construction of ''Containment Systems for Storage and Transport Packagings of Spent Nuclear Fuel and High Level Radioactive Material and Waste'' of Division 3 in Section III of ASME Code (2001 Edition) does not include ductile cast iron in its list of materials permitted for use. The Rules specify required fracture toughness values of ferritic steel material for nominal wall thickness 5/8 to 12 inches (16 to 305 mm). New rule for ductile cast iron for transport packaging of which wall thickness is greater than 12 inches (305mm) is required

Activated sludge model (ASM) based modelling of membrane bioreactor (MBR) processes: a critical review with special regard to MBR specificities.

Science.gov (United States)

Fenu, A; Guglielmi, G; Jimenez, J; Spèrandio, M; Saroj, D; Lesjean, B; Brepols, C; Thoeye, C; Nopens, I

2010-08-01

Membrane bioreactors (MBRs) have been increasingly employed for municipal and industrial wastewater treatment in the last decade. The efforts for modelling of such wastewater treatment systems have always targeted either the biological processes (treatment quality target) as well as the various aspects of engineering (cost effective design and operation). The development of Activated Sludge Models (ASM) was an important evolution in the modelling of Conventional Activated Sludge (CAS) processes and their use is now very well established. However, although they were initially developed to describe CAS processes, they have simply been transferred and applied to MBR processes. Recent studies on MBR biological processes have reported several crucial specificities: medium to very high sludge retention times, high mixed liquor concentration, accumulation of soluble microbial products (SMP) rejected by the membrane filtration step, and high aeration rates for scouring purposes. These aspects raise the question as to what extent the ASM framework is applicable to MBR processes. Several studies highlighting some of the aforementioned issues are scattered through the literature. Hence, through a concise and structured overview of the past developments and current state-of-the-art in biological modelling of MBR, this review explores ASM-based modelling applied to MBR processes. The work aims to synthesize previous studies and differentiates between unmodified and modified applications of ASM to MBR. Particular emphasis is placed on influent fractionation, biokinetics, and soluble microbial products (SMPs)/exo-polymeric substances (EPS) modelling, and suggestions are put forward as to good modelling practice with regard to MBR modelling both for end-users and academia. A last section highlights shortcomings and future needs for improved biological modelling of MBR processes. (c) 2010 Elsevier Ltd. All rights reserved.

Modifications to LLNL Plutonium Packaging Systems (PuPS) to achieve ASME VIII UW-13.2(d) Requirements for the DOE Standard 3013-00 Outer Can Weld

International Nuclear Information System (INIS)

Riley, D; Dodson, K

2001-01-01

The Lawrence Livermore National Laboratory (LLNL) Plutonium Packaging System (PuPS) prepares packages to meet the DOE Standard 3013 (Reference 1). The PuPS equipment was supplied by the British Nuclear Fuels Limited (BNFL). The DOE Standard 3013 requires that the welding of the Outer Can meets ASME Section VIII Division 1 (Reference 2). ASME Section VIII references to ASME Section IX (Reference 3) for most of the welding requirements, but UW-13.2 (d) of Section VIII requires a certain depth and width of the weld. In this document the UW-13.2(d) requirement is described as the (a+b)/2t s ratio. This ratio has to be greater than or equal to one to meet the requirements of UW-13.2(d). The Outer Can welds had not been meeting this requirement. Three methods are being followed to resolve this issue: (1) Modify the welding parameters to achieve the requirement, (2) Submit a weld case to ASME that changes the UW-13.2(d) requirement for their review and approval, and (3) Change the requirements in the DOE-STD-3013. Each of these methods are being pursued. This report addresses how the first method was addressed for the LLNL PuPS. The experimental work involved adjusting the Outer Can rotational speed and the power applied to the can. These adjustments resulted in being able to achieve the ASME VIII, UW-13.2(d) requirement

Methodology and guidelines for evaluation of welded attachments on ASME Class 1,2, or 3 piping

International Nuclear Information System (INIS)

Chang, K.C.; Adams, T.M.; Rodabaugh, E.C.

1985-01-01

The ASME Boiler and Pressure Vessel Code, Section III Subsection NB/NC/ND-3600 provides simplified rules for the evaluation and qualification of piping components. The use of rectangular and hollow, circular welded attachments (hereafter called lugs and trunions) is sometimes necessary in order to provide support for piping systems. The Code provides a set of simple and conservative equations, the associated stress indicies, and specified limitations on their applicability for lugs on Class 1 and Class 2/3 piping in Code Cases N-122 and N-318 respectively. Two new ASME Section III Code Cases, N-391 and N-392, have been prepared to provide the corresponding design guidelines for specific trunion configurations. This paper presents the background on the major concepts involved in the development of these Code Cases and provides some general guidelines to the analysts and designers for the qualification of the attachments not covered by the Code Cases

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo.

Science.gov (United States)

Roux, Clémence; Saviane, Gaëlle; Pini, Jonathan; Belaïd, Nourhène; Dhib, Gihen; Voha, Christine; Ibáñez, Lidia; Boutin, Antoine; Mazure, Nathalie M; Wakkach, Abdelilah; Blin-Wakkach, Claudine; Rouleau, Matthieu

2017-01-01

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs), and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4 + FoxP3 + regulatory T (Treg) cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3 + -Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo . They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo

Directory of Open Access Journals (Sweden)

Clémence Roux

2018-01-01

Full Text Available Despite mesenchymal stromal cells (MSCs are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate. Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs, and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4+ FoxP3+ regulatory T (Treg cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3+-Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo. They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

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Nigel G. Kooreman

2017-08-01

Full Text Available There is growing interest in using embryonic stem cell (ESC and induced pluripotent stem cell (iPSC derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

Trophoblast lineage cells derived from human induced pluripotent stem cells

International Nuclear Information System (INIS)

Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

2013-01-01

Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

Trophoblast lineage cells derived from human induced pluripotent stem cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

2013-07-12

Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

Formation of human hepatocyte-like cells with different cellular phenotypes by human umbilical cord blood-derived cells in the human-rat chimeras

International Nuclear Information System (INIS)

Sun, Yan; Xiao, Dong; Zhang, Ruo-Shuang; Cui, Guang-Hui; Wang, Xin-Hua; Chen, Xi-Gu

2007-01-01

We took advantage of the proliferative and permissive environment of the developing pre-immune fetus to develop a noninjury human-rat xenograft small animal model, in which the in utero transplantation of low-density mononuclear cells (MNCs) from human umbilical cord blood (hUCB) into fetal rats at 9-11 days of gestation led to the formation of human hepatocyte-like cells (hHLCs) with different cellular phenotypes, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), cytokeratin 19 (CK19), cytokeratin 8 (CK8), cytokeratin 18 (CK18), and albumin (Alb), and with some animals exhibiting levels as high as 10.7% of donor-derived human cells in the recipient liver. More interestingly, donor-derived human cells stained positively for CD34 and CD45 in the liver of 2-month-old rat. Human hepatic differentiation appeared to partially follow the process of hepatic ontogeny, as evidenced by the expression of AFP gene at an early stage and albumin gene at a later stage. Human hepatocytes generated in this model retained functional properties of normal hepatocytes. In this xenogeneic system, the engrafted donor-derived human cells persisted in the recipient liver for at least 6 months after birth. Taken together, these findings suggest that the donor-derived human cells with different cellular phenotypes are found in the recipient liver and hHLCs hold biological activity. This humanized small animal model, which offers an in vivo environment more closely resembling the situations in human, provides an invaluable approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future

Using ASM Podcasts to Excite Undergraduate Students about Current Microbiological Research

Directory of Open Access Journals (Sweden)

Stacey E. Lettini

2014-08-01

Full Text Available Innovative technology is often used as a mechanism to engage students in and out of the classroom and can be used to increase critical thinking skills. Podcasts are an excellent way to introduce students to current topics and research in microbiology. The American Society for Microbiology (ASM produces three podcasts that are microbiologically focused: This Week in Microbiology (TWiM, This Week in Parasitology (TWiP, and This Week in Virology (TWiV. These podcasts are usually presented in a manner similar to a journal club, as the presenters regularly invite guests to discuss current research papers. Since students often find reading scientific literature difficult and get bogged down in the details rather than seeing the over-arching purpose of a paper, these podcasts have been used in a General Microbiology course to introduce recent research articles. The students were first assigned an original research article to read and review, and they were asked to generate questions pertaining to things they did not understand. Next, students listened to the corresponding podcast that discussed the article and used it to answer their questions. This was followed by a classroom discussion of the article and the podcast. The ASM podcast helped to demystify original research by providing details of the experimental design and presentation of the results in a language that is more casual and relatable. Students demonstrated greater critical thinking and comprehension of microbiology literature after listening to the podcast. This activity can be used in a variety of courses in the biology curriculum.

c-Myc-Dependent Cell Competition in Human Cancer Cells.

Science.gov (United States)

Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

2017-07-01

Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

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Leonardo D'Aiuto

Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

Batse/Sax and Batse/RXTE-ASM Joint Spectral Studies of GRBs

Science.gov (United States)

Paciesas, William S.

2002-01-01

We proposed to make joint spectral analysis of gamma-ray bursts (GRBs) in the BATSE data base that are located within the fields of view of either the BeppoSAX wide field cameras (WFCs) or the RXTE all-sky monitor (ASM). The very broad-band coverage obtained in this way would facilitate various studies of GRB spectra that are difficult to perform with BATSE data alone. Unfortunately, the termination of the CGRO mission in June 2000 was not anticipated at the time of the proposal, and the sample of common events turned out to be smaller than we would have liked.

Materials and design bases issues in ASME Code Case N-47

International Nuclear Information System (INIS)

Huddleston, R.L.; Swindeman, R.W.

1993-04-01

A preliminary evaluation of the design bases (principally ASME Code Case N-47) was conducted for design and operation of reactors at elevated temperatures where the time-dependent effects of creep, creep-fatigue, and creep ratcheting are significant. Areas where Code rules or regulatory guides may be lacking or inadequate to ensure the operation over the expected life cycles for the next-generation advanced high-temperature reactor systems, with designs to be certified by the US Nuclear Regulatory Commission, have been identified as unresolved issues. Twenty-two unresolved issues were identified and brief scoping plans developed for resolving these issues

Description of comprehensive pump test change to ASME OM code, subsection ISTB

International Nuclear Information System (INIS)

Hartley, R.S.

1994-01-01

The American Society of Mechanical Engineers (ASME) Operations and Maintenance (OM) Main Committee and Board on Nuclear Codes and Standards (BNCS) recently approved changes to ASME OM Code-1990, Subsection ISTB, Inservice Testing of Pumps in Light-Water Reactor Power Plants. The changes will be included in the 1994 addenda to ISTB. The changes, designated as the comprehensive pump test, incorporate a new, improved philosophy for testing safety-related pumps in nuclear power plants. An important philosophical difference between the open-quotes old codeclose quotes inservice testing (IST) requirements and these changes is that the changes concentrate on less frequent, more meaningful testing while minimizing damaging and uninformative low-flow testing. The comprehensive pump test change establishes a more involved biannual test for all pumps and significantly reduces the rigor of the quarterly test for standby pumps. The increased rigor and cost of the biannual comprehensive tests are offset by the reduced cost of testing and potential damage to the standby pumps, which comprise a large portion of the safety-related pumps at most plants. This paper provides background on the pump testing requirements, discusses potential industry benefits of the change, describes the development of the comprehensive pump test, and gives examples and reasons for many of the specific changes. This paper also describes additional changes to ISTB that will be included in the 1994 addenda that are associated with, but not part of, the comprehensive pump test

Proton exchange membrane fuel cells

CERN Document Server

Qi, Zhigang

2013-01-01

Preface Proton Exchange Membrane Fuel CellsFuel CellsTypes of Fuel CellsAdvantages of Fuel CellsProton Exchange Membrane Fuel CellsMembraneCatalystCatalyst LayerGas Diffusion MediumMicroporous LayerMembrane Electrode AssemblyPlateSingle CellStackSystemCell Voltage Monitoring Module (CVM)Fuel Supply Module (FSM)Air Supply Module (ASM)Exhaust Management Module (EMM)Heat Management Module (HMM)Water Management Module (WMM)Internal Power Supply Module (IPM)Power Conditioning Module (PCM)Communications Module (COM)Controls Module (CM)SummaryThermodynamics and KineticsTheoretical EfficiencyVoltagePo

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

OpenAIRE

Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

2016-01-01

Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

The human airway epithelial basal cell transcriptome.

Directory of Open Access Journals (Sweden)

Neil R Hackett

2011-05-01

Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

Development and function of human innate immune cells in a humanized mouse model.

Science.gov (United States)

Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

2014-04-01

Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

Intervención educativa para población infanto-juvenil asmática

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Maria Antonia Acevedo Veja

2015-11-01

Full Text Available Se realizó una intervención educativa a la población infanto-juvenil asmática con edades entre ocho y once años en el policlínico de Manatí, Las Tunas, entre enero y julio de 2012, con el objetivo de evaluar la eficacia de la misma. La población de estudio estuvo formada por los 258 pacientes asmáticos de los 29 Consultorios de Médico de Familia (CMF del área, y la muestra por los 50 seleccionados por muestreo aleatorio simple. La información se obtuvo mediante un cuestionario que fue aplicado antes y después de la intervención educativa y los datos fueron recogidos durante la consulta y de la historia clínica individual. Se concluyó que predominó el sexo masculino, con antecedentes de primera línea de asma bronquial, con factores desencadenantes tales como: infecciones respiratorias agudas, polvo y humedad, así como aquellos que presentan signos clínicos de reflujo y que tienen una mala técnica de aplicación de spray. Se apreció un insuficiente nivel de conocimientos sobre la evaluación de severidad de la crisis, los factores desencadenantes, el manejo del spray y el tratamiento intercrisis, y las exacerbaciones.

CD28 in thymocyte development and peripheral T cell activation in mice exposed to suspended particulate matter

International Nuclear Information System (INIS)

Drela, Nadzieja; Zesko, Izabela; Jakubowska, Martyna; Biernacka, Marzena

2006-01-01

The CD28:B7 signaling pathway is very important for the activity of mature peripheral T lymphocytes and thymocyte development. The proper development of thymocytes into mature single positive CD4 + and CD8 + T cells is crucial for almost all immune functions. In naturally occurring conditions, T cells maturation in the thymus is influenced by environmental agents. The expression of CD28 and the distribution of CD28 low/high thymocytes have been examined at various stages of thymocyte development in BALB/c mice exposed to air-suspended particulate matter (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the total thymocyte population. The increase of the percentage of CD28 low and the decrease of CD28 high thymocytes were observed, which may account for the acceleration of thymocyte development under the conditions of elevated risk resulting from the exposure of animals to environmental xenobiotics. ASM exposure resulted in the increase of the level of proliferation of lymph node T cells induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal expression of CD28 molecule. In contrast, the level of proliferation of spleen T cells was lowered or normal dependently of the concentration of stimuli used for activation. Results of these studies demonstrate that acute exposure of mice to ASM can result in the progression of two contrasting processes in the immune system: upregulation of thymocyte development, which contributes to the maintenance of peripheral T cell pool, and over-activation of lymph node lymphocytes, which may lead to uncontrolled immunostimulation

Utilization of human amniotic mesenchymal cells as feeder layers to sustain propagation of human embryonic stem cells in the undifferentiated state.

Science.gov (United States)

Zhang, Kehua; Cai, Zhe; Li, Yang; Shu, Jun; Pan, Lin; Wan, Fang; Li, Hong; Huang, Xiaojie; He, Chun; Liu, Yanqiu; Cui, Xiaohui; Xu, Yang; Gao, Yan; Wu, Liqun; Cao, Shanxia; Li, Lingsong

2011-08-01

Human embryonic stem (ES) cells are usually maintained in the undifferentiated state by culturing on feeder cells layers of mouse embryonic fibroblasts (MEFs). However, MEFs are not suitable to support human ES cells used for clinical purpose because of risk of zoonosis from animal cells. Therefore, human tissue-based feeder layers need to be developed for human ES cells for clinical purpose. Hereof we report that human amniotic mesenchymal cells (hAMCs) could act as feeder cells for human ES cells, because they are easily obtained and relatively exempt from ethical problem. Like MEFs, hAMCs could act as feeder cells for human ES cells to grow well on. The self-renewal rate of human ES cells cultured on hAMCs feeders was higher than that on MEFs and human amniotic epithelial cells determined by measurement of colonial diameters and growth curve as well as cell cycle analysis. Both immunofluorescence staining and immunoblotting showed that human ES cells cultured on hAMCs expressed stem cell markers such as Oct-3/4, Sox2, and NANOG. Verified by embryoid body formation in vitro and teratoma formation in vivo, we found out that after 20 passages of culture, human ES cells grown on hAMCs feeders could still retain the potency of differentiating into three germ layers. Taken together, our data suggested hAMCs may be safe feeder cells to sustain the propagation of human ES cells in undifferentiated state for future therapeutic use.

A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening.

Science.gov (United States)

An, Steven S; Askovich, Peter S; Zarembinski, Thomas I; Ahn, Kwangmi; Peltier, John M; von Rechenberg, Moritz; Sahasrabudhe, Sudhir; Fredberg, Jeffrey J

2011-01-13

A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

Directory of Open Access Journals (Sweden)

von Rechenberg Moritz

2011-01-01

Full Text Available Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20 and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM. Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Results Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. Conclusions This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

Human monoclonal antibodies reactive with human myelomonocytic leukemia cells.

Science.gov (United States)

Posner, M R; Santos, D J; Elboim, H S; Tumber, M B; Frackelton, A R

1989-04-01

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

Auriculoterapia en pacientes asmáticos

Directory of Open Access Journals (Sweden)

Adolfo González Salvador

1997-04-01

Full Text Available Se realiza un estudio para evaluar la eficacia de la auriculopuntura en 30 asmáticos del área de salud de Aguada de Pasajeros, durante los meses de noviembre de 1992 a abril de 1993. El tratamiento se aplicó durante un mes, con seguimiento durante los 5 meses posteriores. Se observó una disminución en la frecuencia, intensidad y duración de las crisis de asma; la mayoría de los pacientes tuvo una evolución satisfactoria y no se presentaron complicaciones. Se concluye que la auriculoterapia es un método útil en pacientes con asma bronquial debido a su eficacia e inocuidadA study was conducted to evaluate the efficacy of auriculopuncture in 30 asthmatic patients from the health area of Aguada de Pasajeros between November, 1992, and April, 1993. The treatment was applied for a month, with a follow-up during the next 5 months. It was observed a reduction in the frequency, intensity and duration of the asthma crises. Most of the patients had a satisfactory evolution and there were no complications. It is concluded that auriculotherapy is a useful method for patients with bronchial asthma due to its effectiveness and innocuousness.

Evaluation of flaws in ferritic piping: ASME Code Appendix J, Deformation Plasticity Failure Assessment Diagram (DPFAD)

International Nuclear Information System (INIS)

Bloom, J.M.

1991-08-01

This report summarizes the methods and bases used by an ASME Code procedure for the evaluation of flaws in ferritic piping. The procedure is currently under consideration by the ASME Boiler and Pressure Vessel Code Committee of Section 11. The procedure was initially proposed in 1985 for the evaluation of the acceptability of flaws detected in piping during in-service inspection for certain materials, identified in Article IWB-3640 of the ASME Boiler and Pressure Vessel Code Section 11 ''Rules for In-service Inspection of Nuclear Power Plant Components.'' for which the fracture toughness is not sufficiently high to justify acceptance based solely on the plastic limit load evaluation methodology of Appendix C and IWB-3641. The procedure, referred to as Appendix J, originally included two approaches: a J-integral based tearing instability (J-T) analysis and the deformation plasticity failure assessment diagram (DPFAD) methodology. In Appendix J, a general DPFAD approach was simplified for application to part-through wall flows in ferritic piping through the use of a single DPFAD curve for circumferential flaws. Axial flaws are handled using two DPFAD curves where the ratio of flaw depth to wall thickness is used to determine the appropriate DPFAD curve. Flaws are evaluated in Appendix J by comparing the actual pipe applied stress with the allowable stress with the appropriate safety factors for the flaw size at the end of the evaluation period. Assessment points for circumferential and axial flaws are plotted on the appropriate failure assessment diagram. In addition, this report summarizes the experimental test predictions of the results of the Battelle Columbus Laboratory experiments, the Eiber experiments, and the JAERI tests using the Appendix J DPFAD methodology. Lastly, this report also provides guidelines for handling residual stresses in the evaluation procedure. 22 refs., 13 figs., 5 tabs

Signaling hierarchy regulating human endothelial cell development.

Science.gov (United States)

Kelly, Melissa A; Hirschi, Karen K

2009-05-01

Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

A Retrospective Look at 20 Years of ASM Education Programs (1990-2010) and a Prospective Look at the Next 20 Years (2011-2030).

Science.gov (United States)

Chang, Amy

2011-01-01

Professional societies provide visibility and legitimacy to the work of their post secondary educator members, advocate best practices in courses and sponsored student research, and establish deep networks and communities that catalyze members to collectively engage in undergraduate teaching and learning scholarship. Within the American Society for Microbiology (ASM), the Education Board, established in the mid-1970s, assumes this role. I have been fortunate enough to watch several pivotal programs support our growth and change the status quo by providing opportunities for biology educators to flourish. In this retrospective review, the background and details I offer about each initiative help explain ASM Education offerings, how our growth has been supported and how the status quo has changed. In this prospective look, I offer my vision of the future in post secondary education where classroom learning is student-centered and focused on global problems affecting our health and environment. For the profession to proliferate, the ASM must provide members as many opportunities in learning biology as they do with advancing biology to new frontiers.

Challenge - converting to ANSI/ASME NQA Standard 1

International Nuclear Information System (INIS)

Nansen, J.N.

1983-03-01

Prior to August, 1980, Westinghouse Hanford Company operated the Hanford Engineering Development Laboratory Quality Program in accordance with the requirements of RDT F 2-2T and RDT F 2-4T and for a short while to ANSI N45.2. Following the issuance of the national consensus standard ANSI/ ASME NQA Standard 1 in August 1979, and its acceptance by DOE, the Laboratory began making changes to meet these requirements in its internal quality program in August 1980. This was followed with the invoking of these requirements on supplier's programs and all procurement activities in March of 1981. This conversion was completed in approximately six months and provided an opportunity for several improvements. The keynote of this standard is flexibility. A major improvement noted was in the flexibility of application. The program can be tailored to meet specific needs. Vendor surveys under NQA-1 have shown positive results in that the organization and structure of the standard is much easier to follow and understand

Meeting report on the ASM Conference on Mechanisms of Interbacterial Cooperation and Competition.

Science.gov (United States)

Lories, Bram; Parijs, Ilse; Foster, Kevin R; Steenackers, Hans P

2017-08-14

The ASM Conference on Mechanisms of Interbacterial Cooperation and Competition was held in Washington DC, from 1 to 4 March 2017. The conference provided an international forum for sociomicrobiologists from different disciplines to present and discuss new findings. The meeting covered a wide range of topics, spanning molecular mechanisms, ecology, evolution, computation and manipulation of interbacterial interactions, and encompassed social communities in medicine, the natural environment, and industry. This report summarizes the presentations and emerging themes. Copyright © 2017 American Society for Microbiology.

Human regulatory B cells control the TFH cell response.

Science.gov (United States)

Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

2017-07-01

Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Nupack, the new ASME code for radioactive material transportation packaging containments

International Nuclear Information System (INIS)

Turula, P.

1998-01-01

The American Society of Mechanical Engineers (ASME) has added a new division to the nuclear construction section of its Boiler and Pressure Vessel Code (B and PVC). This Division, commonly referred to as Nupack, has been written to provide a consistent set of technical requirements for containment vessels of transportation packagings for high-level radioactive materials. This paper provides an introduction to Nupack, discusses some of its technical provisions, and describes how it can be used for the design and construction of packaging components. Nupack's general provisions and design requirements are emphasized, while treatment of materials, fabrication and inspection is left for another paper

Identification of molecules derived from human fibroblast feeder cells that support the proliferation of human embryonic stem cells

DEFF Research Database (Denmark)

Anisimov, Sergey V.; Christophersen, Nicolaj S.; Correia, Ana S.

2011-01-01

The majority of human embryonic stem cell lines depend on a feeder cell layer for continuous growth in vitro, so that they can remain in an undifferentiated state. Limited knowledge is available concerning the molecular mechanisms that underlie the capacity of feeder cells to support both...... the proliferation and pluripotency of these cells. Importantly, feeder cells generally lose their capacity to support human embryonic stem cell proliferation in vitro following long-term culture. In this study, we performed large-scale gene expression profiles of human foreskin fibroblasts during early...... foreskin fibroblasts to serve as feeder cells for human embryonic stem cell cultures. Among these, the C-KIT, leptin and pigment epithelium-derived factor (PEDF) genes were the most interesting candidates....

Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

Science.gov (United States)

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

Stem cells in the human breast

DEFF Research Database (Denmark)

Petersen, Ole William; Polyak, Kornelia

2010-01-01

The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

The Common Acid Sphingomyelinase Polymorphism p.G508R is Associated with Self-Reported Allergy

Directory of Open Access Journals (Sweden)

Martin Reichel

2014-06-01

Full Text Available Background: Acid sphingomyelinase (ASM is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R was determined from genomic DNA. Activities of secretory (S- and lysosomal (L- ASM were measured in blood plasma and peripheral blood cells respectively. Results: The polymorphism rs1050239 was significantly associated with self-reported allergy (p=4.68×10-4; adjusted p-value for multiple testing 0.007. Allergy was more prevalent in carriers of the minor A allele compared to non-carriers (p=0.00015; odds ratio=6.5, 95% CI 2.15-21.7. S-ASM activity was significantly associated with rs1050239 (p=5.3×10-7 and decreased with the number of A alleles in a gene-dosage dependent manner. In allergic patients, S-ASM activity was moderately decreased (p=0.034. L-ASM activity was significantly lower in subjects homozygous for the minor A allele (p=0.025 but not different between allergic and non-allergic subjects (p=0.318. Conclusion: Our analysis provides evidence for an involvement of ASM in the pathophysiology of allergy, which is in line with previous reports addressing the role of sphingolipids in this disorder. Further studies should clarify the mechanism linking rs1050239 to allergy. The ASM pathway might be useful for predicting allergic disposition and disease course and as a therapeutic target.

Nuclear component design ontology building based on ASME codes

International Nuclear Information System (INIS)

Bao Shiyi; Zhou Yu; He Shuyan

2005-01-01

The adoption of ontology analysis in the study of concept knowledge acquisition and representation for the nuclear component design process based on computer-supported cooperative work (CSCW) makes it possible to share and reuse numerous concept knowledge of multi-disciplinary domains. A practical ontology building method is accordingly proposed based on Protege knowledge model in combination with both top-down and bottom-up approaches together with Formal Concept Analysis (FCA). FCA exhibits its advantages in the way it helps establish and improve taxonomic hierarchy of concepts and resolve concept conflict occurred in modeling multi-disciplinary domains. With Protege-3.0 as the ontology building tool, a nuclear component design ontology based ASME codes is developed by utilizing the ontology building method. The ontology serves as the basis to realize concept knowledge sharing and reusing of nuclear component design. (authors)

Developments on ASME Code Cases to Risk-Informed Repair/Replacement Activities in Support of Risk-Informed Regulation Initiatives

International Nuclear Information System (INIS)

Balkey, Kenneth R.; Holston, William C.

2002-01-01

ASME Code Case N-658, 'Risk-Informed Safety Classification for Use in Risk-Informed Repair/Replacement Activities' and Code Case N-660, 'Alternative Repair/Replacement Requirements For Items Classified In Accordance With Risk-Informed Processes' are being completed to expand the breadth of risk-informed requirements for pressure-retaining items. This initiative, which is built from prior ASME Section XI risk-informed inservice inspection developments over the past decade, has been undertaken in conjunction with U.S. risk-informed regulation efforts. The U.S. Nuclear Regulatory Commission (NRC) is working with the industry on risk informing Title 10 Code of Federal Regulations Part 50 (10CFR50). The Nuclear Regulatory Commission's basic proposal is to allow modification of some of the special treatment requirements of 10CFR50. Their effort is proceeding via an Advanced Notice of Public Rulemaking, March 3, 2000, and an announcement of Availability of Draft Rule Wording, November 29, 2001, to add 10 CFR 50.69, 'Risk-Informed Treatment of Structures, Systems and Components'. A parallel task by the Nuclear Energy Institute (NEI) to develop a guideline on how to implement the results of the rulemaking is also well underway via NEI 00-04 (Draft Revision B), 'Option 2 Implementation Guideline', May 2001. This paper summarizes the content and status of approval of the proposed ASME Code Cases, including how they relate to the above NRC and NEI efforts. Some initial results from trial application of the Code Cases will also be cited. (authors)

Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

International Nuclear Information System (INIS)

Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

1990-01-01

Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

Tuft (caveolated) cells in two human colon carcinoma cell lines.

OpenAIRE

Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

1988-01-01

The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

Modeling human infertility with pluripotent stem cells

Directory of Open Access Journals (Sweden)

Di Chen

2017-05-01

Full Text Available Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse. However, recent work using next generation sequencing, gene editing and differentiation of germline cells from pluripotent stem cells has revealed that the core molecular mechanisms that regulate human germline development are different from rodents. Here, we will discuss the major molecular pathways required for human germline differentiation and how pluripotent stem cells have revolutionized our ability to study the earliest steps in human embryonic lineage specification in order to understand human fertility.

Procedures of ASME code case N-201 for KALIMER. Reactor internal structures

International Nuclear Information System (INIS)

Koo, Gyeong Hoi; Yoo, B.

2001-02-01

The main objective of this report is to describe the design procedure of ASME Boiler and Pressure Vessel Code, Code Case N-201-4, which is an elevated temperature structural design code of the Nuclear reactor internal structures, checking the criteria of stress limit, accumulated inelastic strain and deformation, creep-fatigue damage, and buckling limit. As one of examples, the creep-fatigue damage evaluations are carried out for the KALIMER reactor internal structures of baffle annulus. This report is expected to be very useful in evaluating the structural integrity of the liquid metal reactor operating under an elevated temperature

ASME N510 test results for Savannah River Site AACS filter compartments

Energy Technology Data Exchange (ETDEWEB)

Paul, J.D.; Punch, T.M. [Westinghouse Savannah River Company, Aiken, SC (United States)

1995-02-01

The K-Reactor at the Savannah River Site recently implemented design improvements for the Airborne Activity Confinement System (AACS) by procuring, installing, and testing new Air Cleaning Units, or filter compartments, to ASME AG-11, N509, and N510 requirements. Specifically, these new units provide documentable seismic resistance to a Design Basis Accident earthquake, provide 2 inch adsorber beds with 0.25 second residence time, and meet all AG-1, N509, and N510 requirements for testability and maintainability. This paper presents the results of the Site acceptance testing and discusses an issue associated with sample manifold qualification testing.

Design specifications for ASME B and PV Code Section III nuclear class 1 piping

International Nuclear Information System (INIS)

Richardson, J.A.

1978-01-01

ASME B and PV Code Section III code regulations for nuclear piping requires that a comprehensive Design Specification be developed for ensuring that the design and installation of the piping meets all code requirements. The intent of this paper is to describe the code requirements, discuss the implementation of these requirements in a typical Class 1 piping design specification, and to report on recent piping failures in operating light water nuclear power plants in the US. (author)

Report on ANSI/ASME nuclear air and gas treatment standards for nuclear power plants

International Nuclear Information System (INIS)

Fish, J.F.

1979-01-01

Original N Committee, N45-8, has completed and published through the approved American National Standards Institute process two Standards, N-509 and N-510. This committee has been dissolved and replaced by ASME Committee on Nuclear Air and Gas Treatment with expanded scope to cover not only air cleaning, but thermal treatment equipment. Current efforts are directed to produce Code documents rather than Standards type publications. This report summarizes changed scope, current organization and sub-committee coverage areas

Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

International Nuclear Information System (INIS)

Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan; Cui, Yong-Yao

2012-01-01

Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

Directory of Open Access Journals (Sweden)

Hayato Fukusumi

2016-01-01

Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

ASME code and ratcheting in piping components. Final technical report

International Nuclear Information System (INIS)

Hassan, T.; Matzen, V.C.

1999-01-01

The main objective of this research is to develop an analysis program which can accurately simulate ratcheting in piping components subjected to seismic or other cyclic loads. Ratcheting is defined as the accumulation of deformation in structures and materials with cycles. This phenomenon has been demonstrated to cause failure to piping components (known as ratcheting-fatigue failure) and is yet to be understood clearly. The design and analysis methods in the ASME Boiler and Pressure Vessel Code for ratcheting of piping components are not well accepted by the practicing engineering community. This research project attempts to understand the ratcheting-fatigue failure mechanisms and improve analysis methods for ratcheting predictions. In the first step a state-of-the-art testing facility is developed for quasi-static cyclic and seismic testing of straight and elbow piping components. A systematic testing program to study ratcheting is developed. Some tests have already been performed and the rest will be completed by summer'99. Significant progress has been made in the area of constitutive modeling. A number of sophisticated constitutive models have been evaluated in terms of their simulations for a broad class of ratcheting responses. From the knowledge gained from this evaluation study two improved models are developed. These models are demonstrated to have promise in simulating ratcheting responses in piping components. Hence, implementation of these improved models in widely used finite element programs, ANSYS and/or ABAQUS, is in progress. Upon achieving improved finite element programs for simulation of ratcheting, the ASME Code provisions for ratcheting of piping components will be reviewed and more rational methods will be suggested. Also, simplified analysis methods will be developed for operability studies of piping components and systems. Some of the future works will be performed under the auspices of the Center for Nuclear Power Plant Structures

3 CFR - Guidelines for Human Stem Cell Research

Science.gov (United States)

2010-01-01

... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent...

Progress toward NuPack, the ASME code for Type B containments

International Nuclear Information System (INIS)

Turula, P.

1995-01-01

This paper presented a brief status report on the development of an ASME Code Division for nuclear packaging and discussed some of the more interesting policy decisions as to what is and is not covered in terms of analytical methods, criteria, scope, and other aspects. The process of the development of this Division has been very slow and inconsistent. There were many participants with many diverse interests. The Division 3 rules are close to being ready to be issued. They are a compromise between many needs and the result is certainly not perfect. Opportunities for fine tuning and expanding this document will present themselves after it is issued as future needs become clear

Probing the Mysteries of the X-Ray Binary 4U 1210-64 with ASM, MAXI and Suzaku

Science.gov (United States)

Coley, Joel B.; Corbet, R.; Mukai, K.; Pottschmidt, K.

2013-01-01

Optical and X-ray observations of 4U 1210-64 (1ES 1210-646) suggest that the source is a High Mass X-ray Binary (HMXB) probably powered by the Be mechanism. Data acquired by the RXTE All Sky Monitor (ASM), the ISS Monitor of All-sky X-ray Image (MAXI) and Suzaku provide a detailed temporal and spectral description of this poorly understood source. Long-term data produced by ASM and MAXI indicate that the source shows two distinct high and low states. A 6.7-day orbital period of the system was found in folded light curves produced by both ASM and MAXI. A two day Suzaku observation in Dec. 2010 took place during a transition from the minimum to the maximum of the folded light curve. The two day Suzaku observation reveals large variations in flux indicative of strong orbit to orbit variability. Flares in the Suzaku light curve can reach nearly 1.4 times the mean count rate. From a spectral analysis of the Suzaku data, emission lines in the Fe K alpha region were detected at 6.4 keV, 6.7 keV and 6.97 keV interpreted as FeI, FeXXV and FeXXVI. In addition, emission lines were observed at approximately 1.0 and 2.6 keV, corresponding to NeX and SXVI respectively. Thermal bremsstrahlung or power law models both modified by interstellar and partially covering absorption provide a good fit to the continuum data. This source is intriguing for these reasons: i) No pulse period was observed; ii) 6.7 day orbital period is much less than typical orbital periods seen in Be/X-ray Binaries; iii) The optical companion is a B5V--an unusual spectral class for an HMXB; iv) There are extended high and low X-ray states.

In vitro proliferation of adult human beta-cells.

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Sabine Rutti

Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

Human innate lymphoid cells.

Science.gov (United States)

Mjösberg, Jenny; Spits, Hergen

2016-11-01

Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Present activity in ASME Section XI regarding risk-informed maintenance

International Nuclear Information System (INIS)

Hedden, Owen; Chockie, Alan

2005-01-01

Since 1996 Section XI of the ASME Boiler and Pressure Vessel Code has actively incorporated risk-informed concepts. The risk-informed process provides a framework for allocating inspection resources in a cost-effective manner and helps focus inspections where most critical for plant safety. Based on the success of the risk-informed ISI piping applications at US and non-US plants, Section XI has refined existing Code Cases and expanded the use of the risk-informed process to a variety of high-risk components and systems. The risk informed approach started in the area of inspection and is now being expanded to other plant maintenance activities. This article summarizes the Section XI actions and the continued development of the risk-informed process to improve nuclear plant maintenance. (author)

Some Ethical Concerns About Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Zheng, Yue Liang

2016-10-01

Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy.

Evaluation of conservatisms and environmental effects in ASME Code, Section III, Class 1 fatigue analysis

International Nuclear Information System (INIS)

Deardorff, A.F.; Smith, J.K.

1994-08-01

This report documents the results of a study regarding the conservatisms in ASME Code Section 3, Class 1 component fatigue evaluations and the effects of Light Water Reactor (LWR) water environments on fatigue margins. After review of numerous Class 1 stress reports, it is apparent that there is a substantial amount of conservatism present in many existing component fatigue evaluations. With little effort, existing evaluations could be modified to reduce the overall predicted fatigue usage. Areas of conservatism include design transients considerably more severe than those experienced during service, conservative grouping of transients, conservatisms that have been removed in later editions of Section 3, bounding heat transfer and stress analysis, and use of the ''elastic-plastic penalty factor'' (K 3 ). Environmental effects were evaluated for two typical components that experience severe transient thermal cycling during service, based on both design transients and actual plant data. For all reasonable values of actual operating parameters, environmental effects reduced predicted margins, but fatigue usage was still bounded by the ASME Section 3 fatigue design curves. It was concluded that the potential increase in predicted fatigue usage due to environmental effects should be more than offset by decreases in predicted fatigue usage if re-analysis were conducted to reduce the conservatisms that are present in existing component fatigue evaluations

A strategy for implementation of experience based seismic equipment qualification in IEEE and ASME industry standards

International Nuclear Information System (INIS)

Adams, T.M.

1996-01-01

In the past 20 years, extensive data on the performance of mechanical and electric equipment during actual strong motion earthquakes and seismic qualification tests has been accumulated. Recognizing that an experience based approach provides a technically sound and cost effective method for the seismic qualification of some or certain equipment, the IEEE Nuclear Power Engineering Committee and the ASME Committee on Qualification of Mechanical Equipment established a Special Working Group to investigate the incorporation of experienced based methods into the industry consensus codes and standards currently used in the seismic qualification of Seismic Category Nuclear Power Plant equipment. This paper presents the strategy (course of action) which was developed by the Special Working Group for meeting this objective of incorporation of experience based seismic qualification standards used in the design and seismic qualification of seismic category nuclear power plant equipment. This strategy was recommended to both chartering organizations, the IEEE Nuclear Power Engineering Committee and the ASME Committee on Qualification of Mechanical Equipment for their consideration and implementation. The status of the review and implementation of the Special Working Group's recommended strategy by the sponsoring organization is also discussed

The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

Directory of Open Access Journals (Sweden)

Sonia R Rosner

Full Text Available Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

Appropriate nominal stresses for use with ASME Code pressure-loading stress indices for nozzles

International Nuclear Information System (INIS)

Rodabaugh, E.C.

1976-06-01

This program is part of a cooperative effort with industry to develop and verify analytical methods for assessing the safety of nuclear pressure-vessel and piping-system design. The study of nominal stresses and stress indices described is part of a continuing study of design rules for nozzles in pressure vessels being coordinated by the PVRC Subcommittee on Reinforced Openings and External Loadings. Results from these studies are used by appropriate ASME Code groups in drafting new and improved design rules

Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

Science.gov (United States)

Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

2012-04-01

Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients.

Science.gov (United States)

Hollak, C E M; de Sonnaville, E S V; Cassiman, D; Linthorst, G E; Groener, J E; Morava, E; Wevers, R A; Mannens, M; Aerts, J M F G; Meersseman, W; Akkerman, E; Niezen-Koning, K E; Mulder, M F; Visser, G; Wijburg, F A; Lefeber, D; Poorthuis, B J H M

2012-11-01

Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12 months for pulmonary function tests, 6 minute walk test (6 MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59 years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60 years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11 years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6 years, with some decline in pulmonary function and 6 MWT. Bone

Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

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Xinxin Han

2017-01-01

Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

Haematopoietic stem and progenitor cells from human pluripotent stem cells

Science.gov (United States)

Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

2018-01-01

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

Satellite cells in human skeletal muscle plasticity

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Tim eSnijders

2015-10-01

Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodelling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

Satellite cells in human skeletal muscle plasticity.

Science.gov (United States)

Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

2015-01-01

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

2016-01-01

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

International Nuclear Information System (INIS)

Ramasharma, K.; Li, C.H.

1987-01-01

Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

The contribution of human/non-human animal chimeras to stem cell research

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Sonya Levine

2017-10-01

Full Text Available Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States.

Evaluation of ASME code flaw analysis procedure using the influence function method for application to PWR primary piping

International Nuclear Information System (INIS)

Hong, S.Y.; Yeater, M.L.

1985-01-01

This paper discusses stress intensity factor calculations and fatigue analysis for a PWR primary coolant piping system. The influence function method is applied to evaluate ASME Code Section XI Appendix A ''analysis of flaw indication'' for the application to a PWR primary piping. Results of the analysis are discussed in detail. (orig.)

Code cases for implementing risk-based inservice testing in the ASME OM code

International Nuclear Information System (INIS)

Rowley, C.W.

1996-01-01

Historically inservice testing has been reasonably effective, but quite costly. Recent applications of plant PRAs to the scope of the IST program have demonstrated that of the 30 pumps and 500 valves in the typical plant IST program, less than half of the pumps and ten percent of the valves are risk significant. The way the ASME plans to tackle this overly-conservative scope for IST components is to use the PRA and plant expert panels to create a two tier IST component categorization scheme. The PRA provides the quantitative risk information and the plant expert panel blends the quantitative and deterministic information to place the IST component into one of two categories: More Safety Significant Component (MSSC) or Less Safety Significant Component (LSSC). With all the pumps and valves in the IST program placed in MSSC or LSSC categories, two different testing strategies will be applied. The testing strategies will be unique for the type of component, such as centrifugal pump, positive displacement pump, MOV, AOV, SOV, SRV, PORV, HOV, CV, and MV. A series of OM Code Cases are being developed to capture this process for a plant to use. One Code Case will be for Component Importance Ranking. The remaining Code Cases will develop the MSSC and LSSC testing strategy for type of component. These Code Cases are planned for publication in early 1997. Later, after some industry application of the Code Cases, the alternative Code Case requirements will gravitate to the ASME OM Code as appendices

Code cases for implementing risk-based inservice testing in the ASME OM code

Energy Technology Data Exchange (ETDEWEB)

Rowley, C.W.

1996-12-01

Historically inservice testing has been reasonably effective, but quite costly. Recent applications of plant PRAs to the scope of the IST program have demonstrated that of the 30 pumps and 500 valves in the typical plant IST program, less than half of the pumps and ten percent of the valves are risk significant. The way the ASME plans to tackle this overly-conservative scope for IST components is to use the PRA and plant expert panels to create a two tier IST component categorization scheme. The PRA provides the quantitative risk information and the plant expert panel blends the quantitative and deterministic information to place the IST component into one of two categories: More Safety Significant Component (MSSC) or Less Safety Significant Component (LSSC). With all the pumps and valves in the IST program placed in MSSC or LSSC categories, two different testing strategies will be applied. The testing strategies will be unique for the type of component, such as centrifugal pump, positive displacement pump, MOV, AOV, SOV, SRV, PORV, HOV, CV, and MV. A series of OM Code Cases are being developed to capture this process for a plant to use. One Code Case will be for Component Importance Ranking. The remaining Code Cases will develop the MSSC and LSSC testing strategy for type of component. These Code Cases are planned for publication in early 1997. Later, after some industry application of the Code Cases, the alternative Code Case requirements will gravitate to the ASME OM Code as appendices.

Cell sources for in vitro human liver cell culture models

Science.gov (United States)

Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

2016-01-01

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID:27385595

Development of a software for the ASME code qualification of class-I nuclear piping systems

International Nuclear Information System (INIS)

Mishra, Rajesh; Umashankar, C.; Soni, R.S.; Kushwaha, H.S.; Venkat Raj, V.

1999-11-01

In nuclear industry, the designer often comes across the requirements of Class-1 piping systems which need to be qualified for various normal and abnormal loading conditions. In order to have quick design changes and the design reviews at various stages of design, it is quite helpful if a dedicated software is available for the qualification of Class-1 piping systems. BARC has already purchased a piping analysis software CAESAR-II and has used it for the life extension of heavy water plant, Kota. CAESAR-II facilitates the qualification of Class-2 and Class-3 piping systems among others. However, the present version of CAESAR-II does not have the capability to perform stress checks for the ASME Class-1 nuclear piping systems. With this requirement in mind and the prohibitive costs of commercially available software for the Class-1 piping analyses, it was decided to develop a separate software for this class of piping in such a way that the input and output details of the piping from the CAESAR-II software can be made use of. This report principally contains the details regarding development of a software for codal qualification of Class-1 nuclear piping as per ASME code section-III, NB-3600. The entire work was carried out in three phases. The first phase consisted of development of the routines for reading the output files obtained from the CAESAR-II software, and converting them into required format for further processing. In this phase, the nodewise informations available from the CAESAR-II output file were converted into element-wise informations. The second phase was to develop a general subroutine for reading the various input parameters such as diameter, wall thickness, corrosion allowance, bend radius and also to recognize the bend elements based on the bend radius, directly from the input file of CAESAR-II software. The third phase was regarding the incorporation of the required steps for performing the ASME codal checks as per NB-3600 for Class-1 piping

Nupack, the new Asme code for radioactive material transportation packaging containments

International Nuclear Information System (INIS)

Turula, P.

1998-01-01

The American Society of Mechanical Engineers (ASME) has added a new division to the nuclear construction section of its Boiler and Pressure Vessel Code (B and PVC). This Division, commonly referred to as 'Nupack', has been written to provide a consistent set of technical requirements for containment vessels of transportation packagings for high-level radioactive materials. This paper provides an introduction to Nupack, discusses some of its technical provisions, and describes how it can be used the design and construction of packaging components. Nupack's general provisions and design requirements are emphasized, while treatment of materials, fabrication and inspection is left for another paper. Participation in the Nupack development work described in this paper was supported by the U.S. Department of Energy. (authors)

Human adipose stromal cells expanded in human serum promote engraftment of human peripheral blood hematopoietic stem cells in NOD/SCID mice

International Nuclear Information System (INIS)

Kim, Su Jin; Cho, Hyun Hwa; Kim, Yeon Jeong; Seo, Su Yeong; Kim, Han Na; Lee, Jae Bong; Kim, Jae Ho; Chung, Joo Seop; Jung, Jin Sup

2005-01-01

Human mesenchymal stem cells (hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles, and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle, and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum (FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. In this study, we cultured human adipose stromal cells (hADSC) and bone marrow stroma cells (HBMSC) in human serum (HS) during their isolation and expansion, and demonstrated that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34(+) cells mobilized from bone marrow in NOD/SCID mice. Our results indicate that hADSC and hBMSC cultured in HS can be used for clinical trials of cell and gene therapies, including promotion of engraftment after allogeneic HSC transplantation

Ontogeny of human IgE?expressing B cells and plasma cells

OpenAIRE

Ramadani, F.; Bowen, H.; Upton, N.; Hobson, P. S.; Chan, Y.?C.; Chen, J.?B.; Chang, T. W.; McDonnell, J. M.; Sutton, B. J.; Fear, D. J.; Gould, H. J.

2016-01-01

BACKGROUND: IgE-expressing (IgE+) plasma cells (PCs) provide a continuous source of allergen specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models.OBJECTIVE: To characterise the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs.METHODS: To generate human IgE+ cells we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR we examined the phenoty...

Development of hematopoietic stem and progenitor cells from human pluripotent stem cells.

Science.gov (United States)

Chen, Tong; Wang, Fen; Wu, Mengyao; Wang, Zack Z

2015-07-01

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), provide a new cell source for regenerative medicine, disease modeling, drug discovery, and preclinical toxicity screening. Understanding of the onset and the sequential process of hematopoietic cells from differentiated hPSCs will enable the achievement of personalized medicine and provide an in vitro platform for studying of human hematopoietic development and disease. During embryogenesis, hemogenic endothelial cells, a specified subset of endothelial cells in embryonic endothelium, are the primary source of multipotent hematopoietic stem cells. In this review, we discuss current status in the generation of multipotent hematopoietic stem and progenitor cells from hPSCs via hemogenic endothelial cells. We also review the achievements in direct reprogramming from non-hematopoietic cells to hematopoietic stem and progenitor cells. Further characterization of hematopoietic differentiation in hPSCs will improve our understanding of blood development and expedite the development of hPSC-derived blood products for therapeutic purpose. © 2015 Wiley Periodicals, Inc.

Human stem cells for craniomaxillofacial reconstruction.

Science.gov (United States)

Jalali, Morteza; Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor; Pauklin, Siim; Vallier, Ludovic

2014-07-01

Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction.

The contribution of human/non-human animal chimeras to stem cell research.

Science.gov (United States)

Levine, Sonya; Grabel, Laura

2017-10-01

Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells

OpenAIRE

Romain Barbet; Isabelle Peiffer; Antoinette Hatzfeld; Pierre Charbord; Jacques A. Hatzfeld

2011-01-01

We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs ...

New Monoclonal Antibodies to Defined Cell Surface Proteins on Human Pluripotent Stem Cells.

Science.gov (United States)

O'Brien, Carmel M; Chy, Hun S; Zhou, Qi; Blumenfeld, Shiri; Lambshead, Jack W; Liu, Xiaodong; Kie, Joshua; Capaldo, Bianca D; Chung, Tung-Liang; Adams, Timothy E; Phan, Tram; Bentley, John D; McKinstry, William J; Oliva, Karen; McMurrick, Paul J; Wang, Yu-Chieh; Rossello, Fernando J; Lindeman, Geoffrey J; Chen, Di; Jarde, Thierry; Clark, Amander T; Abud, Helen E; Visvader, Jane E; Nefzger, Christian M; Polo, Jose M; Loring, Jeanne F; Laslett, Andrew L

2017-03-01

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640. © 2016 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Results from Evaluation of Proposed ASME AG-1 Section FI Metal Media Filters - 13063

Energy Technology Data Exchange (ETDEWEB)

Wilson, John A.; Giffin, Paxton K.; Parsons, Michael S.; Waggoner, Charles A. [Institute for Clean Energy Technology, Mississippi State University, 205 Research Blvd Starkville, MS 39759 (United States)

2013-07-01

High efficiency particulate air (HEPA) filtration technology is commonly used in Department of Energy (DOE) facilities that require control of radioactive particulate matter (PM) emissions due to treatment or management of radioactive materials. Although HEPA technology typically makes use of glass fiber media, metal and ceramic media filters are also capable of filtering efficiencies beyond the required 99.97%. Sintered metal fiber filters are good candidates for use in DOE facilities due to their resistance to corrosive environments and resilience at high temperature and elevated levels of relative humidity. Their strength can protect them from high differential pressure or pressure spikes and allow for back pulse cleaning, extending filter lifetime. Use of these filters has the potential to reduce the cost of filtration in DOE facilities due to life cycle cost savings. ASME AG-1 section FI has not been approved due to a lack of protocols and performance criteria for qualifying section FI filters. The Institute for Clean Energy Technology (ICET) with the aid of the FI project team has developed a Section FI test stand and test plan capable of assisting in the qualification ASME AG-1 section FI filters. Testing done at ICET using the FI test stand evaluates resistance to rated air flow, test aerosol penetration and resistance to heated air of the section FI filters. Data collected during this testing consists of temperature, relative humidity, differential pressure, flow rate, upstream particle concentration, and downstream particle concentration. (authors)

Human fetal liver stromal cells that overexpress bFGF support growth and maintenance of human embryonic stem cells.

Directory of Open Access Journals (Sweden)

Jiafei Xi

Full Text Available In guiding hES cell technology toward the clinic, one key issue to be addressed is to culture and maintain hES cells much more safely and economically in large scale. In order to avoid using mouse embryonic fibroblasts (MEFs we isolated human fetal liver stromal cells (hFLSCs from 14 weeks human fetal liver as new human feeder cells. hFLSCs feeders could maintain hES cells for 15 passages (about 100 days. Basic fibroblast growth factor (bFGF is known to play an important role in promoting self-renewal of human embryonic stem (hES cells. So, we established transgenic hFLSCs that stably express bFGF by lentiviral vectors. These transgenic human feeder cells--bFGF-hFLSCs maintained the properties of H9 hES cells without supplementing with any exogenous growth factors. H9 hES cells culturing under these conditions maintained all hES cell features after prolonged culture, including the developmental potential to differentiate into representative tissues of all three embryonic germ layers, unlimited and undifferentiated proliferative ability, and maintenance of normal karyotype. Our results demonstrated that bFGF-hFLSCs feeder cells were central to establishing the signaling network among bFGF, insulin-like growth factor 2 (IGF-2, and transforming growth factor β (TGF-β, thereby providing the framework in which hES cells were instructed to self-renew or to differentiate. We also found that the conditioned medium of bFGF-hFLSCs could maintain the H9 hES cells under feeder-free conditions without supplementing with bFGF. Taken together, bFGF-hFLSCs had great potential as feeders for maintaining pluripotent hES cell lines more safely and economically.

Immortalization of human myogenic progenitor cell clone retaining multipotentiality

International Nuclear Information System (INIS)

Hashimoto, Naohiro; Kiyono, Tohru; Wada, Michiko R.; Shimizu, Shirabe; Yasumoto, Shigeru; Inagawa, Masayo

2006-01-01

Human myogenic cells have limited ability to proliferate in culture. Although forced expression of telomerase can immortalize some cell types, telomerase alone delays senescence of human primary cultured myogenic cells, but fails to immortalize them. In contrast, constitutive expression of both telomerase and the E7 gene from human papillomavirus type 16 immortalizes primary human myogenic cells. We have established an immortalized primary human myogenic cell line preserving multipotentiality by ectopic expression of telomerase and E7. The immortalized human myogenic cells exhibit the phenotypic characteristics of their primary parent, including an ability to undergo myogenic, osteogenic, and adipogenic terminal differentiation under appropriate culture conditions. The immortalized cells will be useful for both basic and applied studies aimed at human muscle disorders. Furthermore, immortalization by transduction of telomerase and E7 represents a useful method by which to expand human myogenic cells in vitro without compromising their ability to differentiate

DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells

Science.gov (United States)

Luo, Li Z.; Park, Sang-Won; Bates, Steven E.; Zeng, Xianmin; Iverson, Linda E.; O'Connor, Timothy R.

2012-01-01

The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use. PMID:22412831

Interaction of Staphylococci with Human B cells.

Directory of Open Access Journals (Sweden)

Tyler K Nygaard

Full Text Available Staphylococcus aureus is a leading cause of human infections worldwide. The pathogen produces numerous molecules that can interfere with recognition and binding by host innate immune cells, an initial step required for the ingestion and subsequent destruction of microbes by phagocytes. To better understand the interaction of this pathogen with human immune cells, we compared the association of S. aureus and S. epidermidis with leukocytes in human blood. We found that a significantly greater proportion of B cells associated with S. epidermidis relative to S. aureus. Complement components and complement receptors were important for the binding of B cells with S. epidermidis. Experiments using staphylococci inactivated by ultraviolet radiation and S. aureus isogenic deletion mutants indicated that S. aureus secretes molecules regulated by the SaeR/S two-component system that interfere with the ability of human B cells to bind this bacterium. We hypothesize that the relative inability of B cells to bind S. aureus contributes to the microbe's success as a human pathogen.

Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

International Nuclear Information System (INIS)

Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

2011-01-01

Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

User-inspired design methodology using Affordance Structure Matrix (ASM for construction projects

Directory of Open Access Journals (Sweden)

Maheswari J. Uma

2017-01-01

Full Text Available Traditionally, design phase of construction projects is often performed with incomplete and inaccurate user preferences. This is due to inefficiencies in the methodologies used for capturing the user requirements that can subsequently lead to inconsistencies and result in non-optimised end-result. Iterations and subsequent reworks due to such design inefficiencies is one of the major reasons for unsuccessful project delivery as they impact project performance measures such as time and cost among others. The existing design theories and practice are primarily based on functional requirements. Function-based design deals with design of artifact alone, which may yield favourable or unfavourable consequences with the design artifact. However, incorporating other interactions such as interactions between user & designer is necessary for optimised end-result. Hence, the objective of this research work is to devise a systematic design methodology considering all the three interactions among users, designers and artefacts for improved design efficiency. In this study, it has been attempted to apply the theory of affordances in a case project that involves the design of an offshore facility. A step-by-step methodology for developing Affordance Structure Matrix (ASM, which integrates House of Quality (HOQ and Design Structure Matrix (DSM, is proposed that can effectively capture the user requirements. HOQ is a popular quality management tool for capturing client requirements and DSM is a matrix-based tool that can capture the interdependency among the design entities. The proposed methodology utilises the strengths of both the tools, as DSM compliments HOQ in the process. In this methodology, different affordances such as AUA (Artifact-User-Affordance, AAA (Artifact-Artifact-Affordance and DDA (Designer-Designer-Affordance are captured systematically. Affordance is considered to be user-driven in this context that is in contrast to prevailing design

Stereological quantification of mast cells in human synovium

DEFF Research Database (Denmark)

Damsgaard, T E; Sørensen, Flemming Brandt; Herlin, T

1999-01-01

Mast cells participate in both the acute allergic reaction as well as in chronic inflammatory diseases. Earlier studies have revealed divergent results regarding the quantification of mast cells in the human synovium. The aim of the present study was therefore to quantify these cells in the human...... synovium, using stereological techniques. Different methods of staining and quantification have previously been used for mast cell quantification in human synovium. Stereological techniques provide precise and unbiased information on the number of cell profiles in two-dimensional tissue sections of......, in this case, human synovium. In 10 patients suffering from osteoarthritis a median of 3.6 mast cells/mm2 synovial membrane was found. The total number of cells (synoviocytes, fibroblasts, lymphocytes, leukocytes) present was 395.9 cells/mm2 (median). The mast cells constituted 0.8% of all the cell profiles...

Twenty years of fracture mechanics and flaw evaluation applications in the ASME Nuclear Code

International Nuclear Information System (INIS)

Riccardella, P.C.

1991-01-01

The paper presents a retrospective on the development and applications of fracture mechanics-based toughness requirements and flaw evaluation methodology in Sections III and XI of the ASME Code. Section III developments range from the rules and requirements for thick section Class 1 pressure vessels to thinner section components in other Classes. Section XI applications include flaw acceptance standards and evaluation methodology for various components ranging from pressure vessels to thins section piping of carbon and austenitic steels. The experience gained in operating plant applications of these rules and procedures are also discussed

Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

Directory of Open Access Journals (Sweden)

Juan Antonio Guadix

2017-12-01

Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

Human mesenchymal stem cells

DEFF Research Database (Denmark)

Abdallah, Basem; Kassem, Moustapha

2008-01-01

Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

T-cell receptor transfer into human T cells with ecotropic retroviral vectors.

Science.gov (United States)

Koste, L; Beissert, T; Hoff, H; Pretsch, L; Türeci, Ö; Sahin, U

2014-05-01

Adoptive T-cell transfer for cancer immunotherapy requires genetic modification of T cells with recombinant T-cell receptors (TCRs). Amphotropic retroviral vectors (RVs) used for TCR transduction for this purpose are considered safe in principle. Despite this, TCR-coding and packaging vectors could theoretically recombine to produce replication competent vectors (RCVs), and transduced T-cell preparations must be proven free of RCV. To eliminate the need for RCV testing, we transduced human T cells with ecotropic RVs so potential RCV would be non-infectious for human cells. We show that transfection of synthetic messenger RNA encoding murine cationic amino-acid transporter 1 (mCAT-1), the receptor for murine retroviruses, enables efficient transient ecotropic transduction of human T cells. mCAT-1-dependent transduction was more efficient than amphotropic transduction performed in parallel, and preferentially targeted naive T cells. Moreover, we demonstrate that ecotropic TCR transduction results in antigen-specific restimulation of primary human T cells. Thus, ecotropic RVs represent a versatile, safe and potent tool to prepare T cells for the adoptive transfer.

Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

International Nuclear Information System (INIS)

Liu, Te; Cheng, Weiwei; Huang, Yongyi; Huang, Qin; Jiang, Lizhen; Guo, Lihe

2012-01-01

Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: ► microRNA-145 inhibits Sox2 expression in human iPS cells. ► microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. ► HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. ► HuAECs feeder layers maintain human iPS cells pluripotency. ► HuAECs negatively regulates the synthesis of

Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

Energy Technology Data Exchange (ETDEWEB)

Liu, Te, E-mail: liute79@yahoo.com [School of Environmental Science and Engineering, Donghua University, Shanghai 201620 (China); Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031 (China); Cheng, Weiwei [International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai 200030 (China); Huang, Yongyi [Laboratoire PROTEE, Batiment R, Universite du Sud Toulon-Var, 83957 LA GARDE Cedex (France); Huang, Qin; Jiang, Lizhen [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Guo, Lihe, E-mail: liute79@yahoo.com [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

2012-02-15

Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: Black-Right-Pointing-Pointer microRNA-145 inhibits Sox2 expression in human iPS cells. Black-Right-Pointing-Pointer microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. Black-Right-Pointing-Pointer HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. Black-Right-Pointing-Pointer HuAECs feeder

21 CFR 864.2280 - Cultured animal and human cells.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cultured animal and human cells. 864.2280 Section... Cultured animal and human cells. (a) Identification. Cultured animal and human cells are in vitro cultivated cell lines from the tissue of humans or other animals which are used in various diagnostic...

Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.

Science.gov (United States)

Westerberg, Sonja; Hagbom, Marie; Rajan, Anandi; Loitto, Vesa; Persson, B David; Allard, Annika; Nordgren, Johan; Sharma, Sumit; Magnusson, Karl-Eric; Arnberg, Niklas; Svensson, Lennart

2018-04-01

Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells. IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41

Culture of human cell lines by a pathogen-inactivated human platelet lysate.

Science.gov (United States)

Fazzina, R; Iudicone, P; Mariotti, A; Fioravanti, D; Procoli, A; Cicchetti, E; Scambia, G; Bonanno, G; Pierelli, L

2016-08-01

Alternatives to the use of fetal bovine serum (FBS) have been investigated to ensure xeno-free growth condition. In this study we evaluated the efficacy of human platelet lysate (PL) as a substitute of FBS for the in vitro culture of some human cell lines. PL was obtained by pools of pathogen inactivated human donor platelet (PLT) concentrates. Human leukemia cell lines (KG-1, K562, JURKAT, HL-60) and epithelial tumor cell lines (HeLa and MCF-7) were cultured with either FBS or PL. Changes in cell proliferation, viability, morphology, surface markers and cell cycle were evaluated for each cell line. Functional characteristics were analysed by drug sensitivity test and cytotoxicity assay. Our results demonstrated that PL can support growth and expansion of all cell lines, although the cells cultured in presence of PL experienced a less massive proliferation compared to those grown with FBS. We found a comparable percentage of viable specific marker-expressing cells in both conditions, confirming lineage fidelity in all cultures. Functionality assays showed that cells in both FBS- and PL-supported cultures maintained their normal responsiveness to adriamycin and NK cell-mediated lysis. Our findings indicate that PL is a feasible serum substitute for supporting growth and propagation of haematopoietic and epithelial cell lines with many advantages from a perspective of process standardization, ethicality and product safety.

Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

Energy Technology Data Exchange (ETDEWEB)

Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

2011-10-28

Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

Male germline stem cells in non-human primates

Directory of Open Access Journals (Sweden)

S. Sharma

2017-09-01

Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

Human induced pluripotent stem cells on autologous feeders.

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Kazutoshi Takahashi

Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

Human interleukin for DA cells or leukemia inhibitory factor is released by Vero cells in human embryo coculture.

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Papaxanthos-Roche, A; Taupin, J L; Mayer, G; Daniel, J Y; Moreau, J F

1994-09-01

In the light of the newly discovered implications of human interleukin for DA cells and leukemia inhibitory factor in embryology, we searched for the presence of this soluble cytokine in the supernatant of Vero cell coculture systems. Using a bioassay as well as a specific ELISA, we demonstrated that Vero cells are able to release large quantities of human interleukin for DA cells and leukemia inhibitory factor in the embryo-growing medium of such cocultures.

Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

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Venkatachalem Sathish

2015-06-01

Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice

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Asami Hanazawa

2018-02-01

Full Text Available The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs, and tumor-associated macrophages (TAMs that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg mouse strain, human interleukin (hIL-6-expressing NOG mice (NOG-hIL-6 transgenic mice. After transplantation of human hematopoietic stem cells (HSCs, the HSC-transplanted NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice showed enhanced human monocyte/macrophage differentiation. A significant number of human monocytes were negative for HLA-DR expression and resembled immature myeloid cells in the spleen and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma-derived cell line producing various factors including IL-6, IL-1β, macrophage colony-stimulating factor (M-CSF, and vascular endothelial growth factor (VEGF, into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of immunoregulatory myeloid cells, and produced immunosuppressive molecules such as arginase-1 (Arg-1, IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to antigen stimulation in in vitro cultures. These results suggest that functional human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will contribute to the development of novel cancer immune therapies targeting immunoregulatory

Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts.

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Motté, Evi; Szepessy, Edit; Suenens, Krista; Stangé, Geert; Bomans, Myriam; Jacobs-Tulleneers-Thevissen, Daniel; Ling, Zhidong; Kroon, Evert; Pipeleers, Daniel

2014-11-01

β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20-30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20-30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation. Copyright © 2014 the American Physiological Society.

Bidirectional enhancing activities between human T cell leukemia-lymphoma virus type I and human cytomegalovirus in human term syncytiotrophoblast cells cultured in vitro.

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Tóth, F D; Aboagye-Mathiesen, G; Szabó, J; Liu, X; Mosborg-Petersen, P; Kiss, J; Hager, H; Zdravkovic, M; Andirkó, I; Aranyosi, J

1995-12-01

The syncytiotrophoblast layer of the human placenta has an important role in limiting transplacental viral spread from mother to fetus. Human cytomegalovirus (HCMV) is capable of establishing a latent infection in syncytiotrophoblast cells, with restriction of gene expression to immediate-early and early proteins. We analyzed the extent of replication of human T cell leukemia-lymphoma virus type I (HTLV-I) in human term syncytiotrophoblasts infected with HTLV-I alone or coinfected with HTLV-I and HCMV. Although syncytiotrophoblasts could be infected with cell-free HTLV-I, no viral protein expression was found in the singly infected cells. On the contrary, coinfection of the cells with HTLV-I and HCMV resulted in simultaneous replication of both viruses. Bidirectional enhancing activities between HTLV-I and HCMV were mediated primarily by the Tax and immediate-early proteins, respectively. The stimulatory effect of HTLV-I Tax on HCMV replication appeared to be mediated partly by tumor necrosis factor beta and transforming growth factor beta-1. We observed formation of pseudotypes with HTLV-I nucleocapsids within HCMV envelopes, whereas HCMV was not pseudotyped by HTLV-I envelopes in dually infected syncytiotrophoblast cells. Our data suggest that in vivo dual infection of syncytiotrophoblast cells with HTLV-I and HCMV may facilitate the transplacental transmission of both viruses.

Sensing radiosensitivity of human epidermal stem cells

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Rachidi, Walid; Harfourche, Ghida; Lemaitre, Gilles; Amiot, Franck; Vaigot, Pierre; Martin, Michele T.

2007-01-01

Purpose: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. Methods and materials: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2 Gy with the XTT assay at 72 h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. Results: Cell sorting based on two membrane proteins, α6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2 Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. Conclusion: These results show for the first time that keratinocyte

46 CFR 56.60-1 - Acceptable materials and specifications (replaces 123 and Table 126.1 in ASME B31.1).

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2010-10-01

... Fittings and Other Piping Components—Magnetic Particle Examination Method. SP-55 Quality Standard for Steel... certification, use is limited to applications within heat exchangers. 12 Hydrostatic testing of these fittings... and Seamless Wrought Steel Pipe. ASME B36.19M 2004 Stainless Steel Pipe. American Society for Testing...

New frontiers in human cell biology and medicine: can pluripotent stem cells deliver?

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Goldstein, Lawrence S B

2012-11-12

Human pluripotent stem cells provide enormous opportunities to treat disease using cell therapy. But human stem cells can also drive biomedical and cell biological discoveries in a human model system, which can be directly linked to understanding disease or developing new therapies. Finally, rigorous scientific studies of these cells can and should inform the many science and medical policy issues that confront the translation of these technologies to medicine. In this paper, I discuss these issues using amyotrophic lateral sclerosis as an example.

The lifetime of hypoxic human tumor cells

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Durand, Ralph E.; Sham, Edward

1998-01-01

Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

The ASME section XI code, past, present, and future

International Nuclear Information System (INIS)

Anderson, W.F.; Bush, S.H.; Chockie, L.J.

1982-01-01

A little over a decade has passed since the first drafts of the Codes effecting the program of inservice inspections in the United States have been implemented and enforced in operating power plants. During the ensuing years, advantage has been taken of results of the application of the program of inspections and tests. In several instances, the Code has been revised to correct deficiencies, and additional rules have been added to accommodate additional systems and portions of the plant which were deemed to also be important to safety. Additional rules have now been published to recognize the liquid metal cooled reactor systems and the gas cooled reactor systems along with the water cooled reactor systems. While the past and the present can be stated with considerable certainty, opinions of the authors, each of whom is a member of the American Society of Mechanical Engineers (ASME) Code Committee, are advanced as to their plans which will reveal the direction the Code is projected to follow in the future. (author)

Toxicity of diuron in human cancer cells.

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Huovinen, Marjo; Loikkanen, Jarkko; Naarala, Jonne; Vähäkangas, Kirsi

2015-10-01

Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

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Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-11-19

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

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Chen Chang-Jie

2010-10-01

Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

Low antigenicity of hematopoietic progenitor cells derived from human ES cells

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Eun-Mi Kim

2010-02-01

Full Text Available Eun-Mi Kim1, Nicholas Zavazava1,21Department of Internal Medicine, University of Iowa and Veterans Affairs Medical Center, Iowa City, Iowa, USA; 2Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USAAbstract: Human embryonic stem (hES cells are essential for improved understanding of diseases and our ability to probe new therapies for use in humans. Currently, bone marrow cells and cord blood cells are used for transplantation into patients with hematopoietic malignancies, immunodeficiencies and in some cases for the treatment of autoimmune diseases. However, due to the high immunogenicity of these hematopoietic cells, toxic regimens of drugs are required for preconditioning and prevention of rejection. Here, we investigated the efficiency of deriving hematopoietic progenitor cells (HPCs from the hES cell line H13, after co-culturing with the murine stromal cell line OP9. We show that HPCs derived from the H13 ES cells poorly express major histocompatibility complex (MHC class I and no detectable class II antigens (HLA-DR. These characteristics make hES cell-derived hematopoietic cells (HPCs ideal candidates for transplantation across MHC barriers under minimal immunosuppression.Keywords: human embryonic stem cells, H13, hematopoiesis, OP9 stromal cells, immunogenicity

Identification of proteins specific for human herpesvirus 6-infected human T cells

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Balachandran, N.; Amelse, R.E.; Zhou, W.W.; Chang, C.K.

1989-01-01

Proteins specific for human herpesvirus 6 (HHV-6)-infected human T cells (HSB-2) were examined by using polyclonal rabbit antibodies and monoclonal antibodies against HHV-6-infected cells and human sera. More than 20 proteins and six glycoproteins specific for HHV-6-infected cells were identified from [ 35 S]methionine- and [ 3 H]glucosamine-labeled total-cell extracts. Polyclonal rabbit antibodies immunoprecipitated 33 [ 35 S]methionine-labeled HHV-6-specific polypeptides with approximate molecular weights ranging from 180,000 to 31,000. In immunoprecipitation and Western immunoblot reactions, a patient's serum also recognized more than 30 HHV-6-specific proteins and seven glycoproteins. In contrast, sera from individuals with high-titered antibodies against other human herpesviruses reacted with fewer HHV-6-infected cell proteins, and only a 135,000-M r polypeptide was prominent. Monoclonal antibodies to HHV-6-infected cells reacted with single and multiple polypeptides specific for virus-infected cells and immunoprecipitated three distinct sets of glycoproteins, which were designated gp105k and gp82k, gp116k, gp64k, and gp54k, and gp102k

Identification of proteins specific for human herpesvirus 6-infected human T cells

International Nuclear Information System (INIS)

Balachandran, N.; Amelse, R.E.; Zhou, W.W.; Chang, C.K.

1989-01-01

Proteins specific for human herpesvirus 6 (HHV-6)-infected human T cells (HSB-2) were examined by using polyclonal rabbit antibodies and monoclonal antibodies against HHV-6-infected cells and human sera. More than 20 proteins and six glycoproteins specific for HHV-6-infected cells were identified from [ 35 S]methionine- and [ 3 H]glucosamine-labeled total-cell extracts. Polyclonal rabbit antibodies immunoprecipitated 33 [ 35 S]methionine-labeled HHV-6-specific polypeptides with approximate molecular weights ranging from 180,000 to 31,000. In immunoprecipitation and Western immunoblot reactions, a patient's serum also recognized more than 30 HHV-6-specific proteins and seven glycoproteins. In contrast, sera from individuals with high-titered antibodies against other human herpes viruses reacted with few HHV-6-infected cell proteins, and only a 135,000-M/sub r/ polypeptide was prominent. Monoclonal antibodies to HHV-6-infected cells reacted with single and multiple polypeptides specific for virus-infected cells and immunoprecipitated three distinct sets of glycoproteins, which were designated gp105K and gp92k, gp116k, gp64k, and gp54k, and gp102k

The response of human and rodent cells to hyperthermia

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Roizin-Towle, L.; Pirro, J.P.

1991-01-01

Inherent cellular radiosensitivity in vitro has been shown to be a good predictor of human tumor response in vivo. In contrast, the importance of the intrinsic thermosensitivity of normal and neoplastic human cells as a factor in the responsiveness of human tumors to adjuvant hyperthermia has never been analyzed systematically. A comparison of thermal sensitivity and thermo-radiosensitization in four rodent and eight human-derived cell lines was made in vitro. Arrhenius plots indicated that the rodent cells were more sensitive to heat killing than the human, and the break-point was 0.5 degrees C higher for the human than rodent cells. The relationship between thermal sensitivity and the interaction of heat with X rays at low doses was documented by thermal enhancement ratios (TER's). Cells received either a 1 hr exposure to 43 degrees C or a 20 minute treatment at 45 degrees C before exposure to 300 kVp X rays. Thermal enhancement ratios ranged from 1.0 to 2.7 for human cells heated at 43 degrees C and from 2.1 to 5.3 for heat exposures at 45 degrees C. Thermal enhancement ratios for rodent cells were generally 2 to 3 times higher than for human cells, because of the fact that the greater thermosensitivity of rodent cells results in a greater enhancement of radiation damage. Intrinsic thermosensitivity of human cells has relevance to the concept of thermal dose; intrinsic thermo-radiosensitization of a range of different tumor cells is useful in documenting the interactive effects of radiation combined with heat

Robust boundary detection of left ventricles on ultrasound images using ASM-level set method.

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Zhang, Yaonan; Gao, Yuan; Li, Hong; Teng, Yueyang; Kang, Yan

2015-01-01

Level set method has been widely used in medical image analysis, but it has difficulties when being used in the segmentation of left ventricular (LV) boundaries on echocardiography images because the boundaries are not very distinguish, and the signal-to-noise ratio of echocardiography images is not very high. In this paper, we introduce the Active Shape Model (ASM) into the traditional level set method to enforce shape constraints. It improves the accuracy of boundary detection and makes the evolution more efficient. The experiments conducted on the real cardiac ultrasound image sequences show a positive and promising result.

Application of the ASME-code-case N 47 to a typical thickwalled HTR-component made of Incoloy 800

International Nuclear Information System (INIS)

Kemter, F.; Schmidt, A.

Several components of the HTR-plant are exposed to temperatures beyond 500 0 C, i.e. within the high-temperature range. The service life of those components is not only limited by fatigue damage but also mainly by creep damage and accumulated inelastic strain. These can be conservatively estimated according to the ASME-Code (high temperature part CC N47) by means of the results of elastic calculations, yet this simplified method to provide evidence often leads to calculated overloads such as the present case of the live steam collector of the steam generator of a HTR. For providing the evidence that the actual loads of the component are within permissible limits, comprehensive inelastic analyses have to be referred to in such a case. The two-dimensional inelastic analysis which is reported here in detail shows that the creep and fatigue failure as well as the inelastic extensions of the live steam collectors accumulated during the service time are below the permissible limit stated in the ASME-Code and failure of those components while used in the reactor can this be excluded. (orig.) [de

Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication

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Jide Tian

2017-01-01

Full Text Available The activation of β-cell’s A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS. Lesogaberan (AZD3355 is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD that appears to be safe for human use. This study tested the hypothesis that lesogaberan could be repurposed to promote human islet cell survival and β-cell replication. Treatment with lesogaberan significantly enhanced replication of human islet cells in vitro, which was abrogated by a GABAB-R antagonist. Immunohistochemical analysis of human islets that were grafted into immune-deficient mice revealed that oral treatment with lesogaberan promoted human β-cell replication and islet cell survival in vivo as effectively as GABA (which activates both GABAA-Rs and GABAB-Rs, perhaps because of its more favorable pharmacokinetics. Lesogaberan may be a promising drug candidate for clinical studies of diabetes intervention and islet transplantation.

Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

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Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

2014-01-01

Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

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Kirstin B. Langer

2018-04-01

Full Text Available Summary: Retinal ganglion cells (RGCs are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs, this class of cell is remarkably diverse, comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models, but less attention has been paid to human RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics, confirming the combinatorial expression of molecular markers associated with these subtypes, and also provided insight into more subtype-specific markers. Thus, the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs. : In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes. Keywords: iPSC, retina, retinal ganglion cell, RGC subtype, stem cell, ipRGC, alpha RGC, direction selective RGC, RNA-seq

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

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Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells.

Science.gov (United States)

Zhang, Yue-Hui; Li, Hai-Dong; Li, Bo; Jiang, Sheng-Dan; Jiang, Lei-Sheng

2014-02-01

Panax ginseng is a Chinese medicinal herb. Ginsenosides are the main bioactive components of P. ginseng, and ginsenoside Rg3 is the primary ginsenoside. Ginsenosides can potently kill various types of cancer cells. The present study was designed to evaluate the potential genotoxicity of ginsenoside Rg3 in human osteosarcoma cells and the protective effect of ginsenoside Rg3 with respect to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced DNA damage and apoptosis in a normal human cell line (human fibroblasts). Four human osteosarcoma cell lines (MG-63, OS732, U-2OS and HOS cells) and a normal human cell line (human fibroblasts) were employed to investigate the cytotoxicity of ginsenosides Rg3 by MTT assay. Alkaline comet assay and γH2AX focus staining were used to detect the DNA damage in MG-63 and U-2OS cells. The extent of cell apoptosis was determined by flow cytometry and a DNA ladder assay. Our results demonstrated that the cytotoxicity of ginsenoside Rg3 was dose-dependent in the human osteosarcoma cell lines, and MG-63 and U-2OS cells were the most sensitive to ginsenoside Rg3. As expected, compared to the negative control, ginsenoside Rg3 significantly increased DNA damage in a concentration-dependent manner. In agreement with the comet assay data, the percentage of γH2AX-positive MG-63 and U-2OS cells indicated that ginsenoside Rg3 induced DNA double-strand breaks in a concentration-dependent manner. The results also suggest that ginsenoside Rg3 reduces the extent of MNNG-induced DNA damage and apoptosis in human fibroblasts.

Genetically-modified pig mesenchymal stromal cells: xenoantigenicity and effect on human T-cell xenoresponses.

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Ezzelarab, Mohamed; Ezzelarab, Corin; Wilhite, Tyler; Kumar, Goutham; Hara, Hidetaka; Ayares, David; Cooper, David K C

2011-01-01

Mesenchymal stromal cells (MSC) are being investigated as immunomodulatory therapy in the field of transplantation, particularly islet transplantation. While MSC can regenerate across species barriers, the immunoregulatory influence of genetically modified pig MSC (pMSC) on the human and non-human primate T-cell responses has not been studied. Mesenchymal stromal cells from wild-type (WT), α1,3-galactosyltransferase gene knockout (GTKO) and GTKO pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46) were isolated and tested for differentiation. Antibody binding and T-cell responses to WT and GTKO pMSC in comparison with GTKO pig aortic endothelial cells (pAEC) were investigated. The expression of swine leukocyte antigen (SLA) class II (SLA II) was tested. Costimulatory molecules CD80 and CD86 mRNA levels were measured. Human T-cell proliferation and the production of pro-inflammatory cytokines in response to GTKO and GTKO/CD46 pMSC in comparison with human MSC (hMSC) were evaluated. α1,3-galactosyltransferase gene knockout and GTKO/CD46 pMSC isolation and differentiation were achieved in vitro. Binding of human antibodies and T-cell responses were lower to GTKO than those to WT pMSC. Human and baboon (naïve and sensitized) antibody binding were significantly lower to GTKO pMSC than to GTKO pAEC. Before activation, human CD4(+) T-cell response to GTKO pMSC was significantly weaker than that to GTKO pAEC, even after pIFN-γ activation. More than 99% of GTKO/CD46 pMSC expressed hCD46. Human peripheral blood mononuclear cells and CD4(+) T-cell responses to GTKO and GTKO/CD46 pMSC were comparable with those to hMSC, and all were significantly lower than to GTKO pAEC. GTKO/CD46 pMSC downregulated human T-cell proliferation as efficiently as hMSC. The level of proinflammatory cytokines IL-2, IFN-γ, TNF-α, and sCD40L correlated with the downregulation of T-cell proliferation by all types of MSC. Genetically modified pMSC is significantly less

A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

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Guohua Yi

2017-11-01

Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

Differentiation of insulin-producing cells from human neural progenitor cells.

Directory of Open Access Journals (Sweden)

Yuichi Hori

2005-04-01

Full Text Available BACKGROUND: Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. METHODS AND FINDINGS: Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs. During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. CONCLUSION: Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

Human leukaemic cells

International Nuclear Information System (INIS)

Andronikashvili, E.L.; Mosulishvili, L.M.; Belokobil'skiy, A.I.; Kharabadze, N.E.; Shonia, N.I.; Desai, L.S.; Foley, G.E.

1976-01-01

The results of the determination of trace elements in nucleic acids and histones in human leukaemic cells by activation analysis are reported. The Cr 2+ , Fe 2+ , Zn 2+ , Co 2+ and Sb 2+ content of DNA and RNA of leukaemic cells compared to that of lymphocytes from a patient with infectious mononucleosis or a normal donor are shown tabulated. Similar comparisons are shown for the same trace metal content of histones isolated from the same type of cells. It is felt that the results afford further interesting speculation that trace metals may be involved in the interactions between histones and DNA (especially at the binding sites of histones to DNA), which affect transcription characteristics. (U.K.)

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

Science.gov (United States)

Stampfer, Martha R; Garbe, James C

2015-02-24

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

A Chemical Probe that Labels Human Pluripotent Stem Cells

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Nao Hirata

2014-03-01

Full Text Available A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1] that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1 and ABCG2 (BCRP, both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

Generation of Oligodendrogenic Spinal Neural Progenitor Cells From Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Khazaei, Mohamad; Ahuja, Christopher S; Fehlings, Michael G

2017-08-14

This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation. Throughout, cell exposure to growth factors and patterning morphogens has been optimized for both concentration and timing, based on the literature and empirical experience, resulting in a robust and highly efficient protocol. Using this derivation procedure, it is possible to obtain millions of oligodendrogenic-NPCs within 40 days of initial cell plating which is substantially shorter than other protocols for similar cell types. This protocol has also been optimized to use translationally relevant human iPSCs as the parent cell line. The resultant cells have been extensively characterized both in vitro and in vivo and express key markers of an oligodendrogenic lineage. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley and Sons, Inc.