Academic literature on the topic 'Integrin LFA-1'
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Journal articles on the topic "Integrin LFA-1"
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Leitinger, Birgit, and Nancy Hogg. "Effects of I Domain Deletion on the Function of the β2 Integrin Lymphocyte Function-associated Antigen-1." Molecular Biology of the Cell 11, no. 2 (February 2000): 677–90. http://dx.doi.org/10.1091/mbc.11.2.677.
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A subset of integrin α subunits contain an I domain, which is important for ligand binding. We have deleted the I domain from the β2 integrin lymphocyte function-asssociated antigen-1 (LFA-1) and expressed the resulting non–I domain-containing integrin (ΔI-LFA-1) in an LFA-1-deficient T cell line. ΔI-LFA-1 showed no recognition of LFA-1 ligands, confirming the essential role of the I domain in ligand binding. Except for I domain monoclonal antibodies (mAbs), ΔI-LFA-1 was recognized by a panel of anti-LFA-1 mAbs similarly to wild-type LFA-1. However, ΔI-LFA-1 had enhanced expression of seven mAb epitopes that are associated with β2 integrin activation, suggesting that it exhibited an “active” conformation. In keeping with this characteristic, ΔI-LFA-1 induced constitutive activation of α4β1 and α5β1, suggesting intracellular signaling to these integrins. This “cross-talk” was not due to an effect on β1 integrin affinity. However, the enhanced activity was susceptible to inhibition by cytochalasin D, indicating a role for the cytoskeleton, and also correlated with clustering of β1 integrins. Thus, removal of the I domain from LFA-1 created an integrin with the hallmarks of a constitutively active receptor mediating signals into the cell. These findings suggest a key role for the I domain in controlling integrin activity.
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Lub, M., S. J. van Vliet, S. P. Oomen, R. A. Pieters, M. Robinson, C. G. Figdor, and Y. van Kooyk. "Cytoplasmic tails of beta 1, beta 2, and beta 7 integrins differentially regulate LFA-1 function in K562 cells." Molecular Biology of the Cell 8, no. 4 (April 1997): 719–28. http://dx.doi.org/10.1091/mbc.8.4.719.
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The beta 2 integrin lymphocyte function-associated antigen 1 (LFA-1) mediates activation-dependent adhesion of lymphocytes. To investigate whether lymphocyte-specific elements are essential for LFA-1 function, we expressed LFA-1 in the erythroleukemic cell line K562, which expresses only the integrin very late antigen 5. We observed that LFA-1-expressing K562 cannot bind to intercellular adhesion molecule 1-coated surfaces when stimulated by phorbol 12-myristate 13-acetate (PMA), whereas the LFA-1-activating antibody KIM185 markedly enhanced adhesion. Because the endogenously expressed beta 1 integrin very late antigen 5 is readily activated by PMA, we investigated the role of the cytoplasmic domain of distinct beta subunits in regulating LFA-1 function. Transfection of chimeric LFA-1 receptors in K562 cells reveals that replacement of the beta 2 cytoplasmic tail with the beta 1 but not the beta 7 cytoplasmic tail completely restores PMA responsiveness of LFA-1, whereas a beta 2 cytoplasmic deletion mutant of LFA-1 is constitutively active. Both deletion of the beta 2 cytoplasmic tail or replacement by the beta 1 cytoplasmic tail alters the localization of LFA-1 into clusters, thereby regulating LFA-1 activation and LFA-1-mediated adhesion to intercellular adhesion molecule 1. These data demonstrate that distinct signaling routes activate beta 1 and beta 2 integrins through the beta-chain and hint at the involvement of lymphocyte-specific signal transduction elements in beta 2 and beta 7 integrin activation that are absent in the nonlymphocytic cell line K562.
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Dransfield, I., C. Cabañas, A. Craig, and N. Hogg. "Divalent cation regulation of the function of the leukocyte integrin LFA-1." Journal of Cell Biology 116, no. 1 (January 1, 1992): 219–26. http://dx.doi.org/10.1083/jcb.116.1.219.
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The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte integrin functional activity. We have assessed the role of divalent cations Mg2+, Ca2+, and Mn2+ in LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) and induction of the divalent cation-dependent epitope recognized by mAb 24. Manganese strongly promoted both expression of the 24 epitope and T cell binding to ICAM-1 via LFA-1, suggesting that Mn2+ is able to directly alter the conformation of LFA-1 in a manner that favors ligand binding. Since Mn2+ also promotes functional activity of other integrins, parallels in mechanism of ligand binding may span the integrin family. In contrast, induction of 24 epitope expression by Mg2+ required removal of Ca2+ from T cell LFA-1 with EGTA. Furthermore, binding of mAb 24 to T cell LFA-1 in the presence of either Mn2+ or Mg2+ was found to be specifically inhibited by Ca2+, suggestive of a negative regulatory role for Ca2+ in the control of leukocyte integrin function. Analysis of T cell binding to ICAM-1 via LFA-1 in the presence of Mg2+ or Mn2+, confirmed that Ca2+ exerted inhibitory effects upon LFA-1 function. The implication of our findings is that Ca2+ bound with relatively high affinity to LFA-1 may serve to maintain an inactive state. Thus induction of function and 24 epitope expression may occur as a result of displacement of Ca2+ from leukocyte integrins or alternatively, such activators may be able to impose the required conformational change in the presence of bound Ca2+.
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Leitinger, Birgit, and Nancy Hogg. "The involvement of lipid rafts in the regulation of integrin function." Journal of Cell Science 115, no. 5 (March 1, 2002): 963–72. http://dx.doi.org/10.1242/jcs.115.5.963.
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Integrin activity on cells such as T lymphocytes is tightly controlled. Here we demonstrate a key role for lipid rafts in regulating integrin function. Without stimulation integrin LFA-1 is excluded from lipid rafts, but following activation LFA-1 is mobilised to the lipid raft compartment. An LFA-1 construct from which the I domain has been deleted mimics activated integrin and is constitutively found in lipid rafts. This correlation between integrin activation and raft localisation extends to a second integrin,α4β1, and the clustering of α4β1 is also raft dependent. Both LFA-1 and α4β1-mediated adhesion is dependent upon intact lipid rafts providing proof of the functional relevance of the lipid raft localisation. Finally we find that non-raft integrins are excluded from the rafts by cytoskeletal constraints. The presence of integrin in lipid rafts under stimulating conditions that activate these receptors strongly indicates that the rafts have a key role in positively regulating integrin activity.
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Geijtenbeek, Teunis B. H., Yvette van Kooyk, Sandra J. van Vliet, Maurits H. Renes, Reinier A. P. Raymakers, and Carl G. Figdor. "High Frequency of Adhesion Defects in B-Lineage Acute Lymphoblastic Leukemia." Blood 94, no. 2 (July 15, 1999): 754–64. http://dx.doi.org/10.1182/blood.v94.2.754.
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Abstract Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)– and very late activation antigen-4 (VLA-4)–mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10− and CD10+ (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1– and/or VLA-4–mediated adhesion defects. Five patients contained CD10+ cells that did not exhibit any LFA-1–mediated adhesion due to the lack of LFA-1 surface expression. The CD10+ cells from 10 ALL patients expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 13-acetate (PMA), whereas the CD10− cells expressed a functional LFA-1. Seven patients contained CD10+ cells that expressed a PMA-unresponsive form of VLA-4. The PMA unresponsiveness of the integrins LFA-1 and VLA-4 expressed by the CD10+ cells may be due to mutations in the integrins itself, in protein kinases, or in other intracellular molecules involved in integrin adhesion. These data clearly demonstrate the importance of investigating integrin function in addition to integrin surface expression. The strikingly high frequency (85%) of adhesion defects in ALL could suggest a causal relationship between integrin-mediated adhesion and B-lineage ALL.
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Geijtenbeek, Teunis B. H., Yvette van Kooyk, Sandra J. van Vliet, Maurits H. Renes, Reinier A. P. Raymakers, and Carl G. Figdor. "High Frequency of Adhesion Defects in B-Lineage Acute Lymphoblastic Leukemia." Blood 94, no. 2 (July 15, 1999): 754–64. http://dx.doi.org/10.1182/blood.v94.2.754.414k11_754_764.
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Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)– and very late activation antigen-4 (VLA-4)–mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10− and CD10+ (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1– and/or VLA-4–mediated adhesion defects. Five patients contained CD10+ cells that did not exhibit any LFA-1–mediated adhesion due to the lack of LFA-1 surface expression. The CD10+ cells from 10 ALL patients expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 13-acetate (PMA), whereas the CD10− cells expressed a functional LFA-1. Seven patients contained CD10+ cells that expressed a PMA-unresponsive form of VLA-4. The PMA unresponsiveness of the integrins LFA-1 and VLA-4 expressed by the CD10+ cells may be due to mutations in the integrins itself, in protein kinases, or in other intracellular molecules involved in integrin adhesion. These data clearly demonstrate the importance of investigating integrin function in addition to integrin surface expression. The strikingly high frequency (85%) of adhesion defects in ALL could suggest a causal relationship between integrin-mediated adhesion and B-lineage ALL.
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Luo, Xuan, Valentine Seveau de Noray, Laurene Aoun, Martine Biarnes-Pelicot, Pierre-Olivier Strale, Vincent Studer, Marie-Pierre Valignat, and Olivier Theodoly. "Lymphocytes perform reverse adhesive haptotaxis mediated by LFA-1 integrins." Journal of Cell Science 133, no. 16 (July 21, 2020): jcs242883. http://dx.doi.org/10.1242/jcs.242883.
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ABSTRACTCell guidance by anchored molecules, or haptotaxis, is crucial in development, immunology and cancer. Adhesive haptotaxis, or guidance by adhesion molecules, is well established for mesenchymal cells such as fibroblasts, whereas its existence remains unreported for amoeboid cells that require less or no adhesion in order to migrate. We show that, in vitro, amoeboid human T lymphocytes develop adhesive haptotaxis mediated by densities of integrin ligands expressed by high endothelial venules. Moreover, lymphocytes orient towards increasing adhesion with VLA-4 integrins (also known as integrin α4β1), like all mesenchymal cells, but towards decreasing adhesion with LFA-1 integrins (also known as integrin αLβ4), which has not previously been observed. This counterintuitive ‘reverse haptotaxis’ cannot be explained by existing mechanisms of mesenchymal haptotaxis involving either competitive anchoring of cell edges under tension or differential integrin-activated growth of lamellipodia, because they both favor orientation towards increasing adhesion. The mechanisms and functions of amoeboid adhesive haptotaxis remain unclear; however, multidirectional integrin-mediated haptotaxis might operate around transmigration ports on endothelia, stromal cells in lymph nodes, and inflamed tissue where integrin ligands are spatially modulated.
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Porter, Joanna C., and Nancy Hogg. "Integrin Cross Talk: Activation of Lymphocyte Function-associated Antigen-1 on Human T Cells Alters α4β1- and α5β1-mediated Function." Journal of Cell Biology 138, no. 6 (September 22, 1997): 1437–47. http://dx.doi.org/10.1083/jcb.138.6.1437.
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A regulated order of adhesion events directs leukocytes from the vascular compartment into injured tissues in response to inflammatory stimuli. We show that on human T cells, the interaction of the β2 integrin leucocyte function–associated antigen-1 (LFA-1) with its ligand intercellular adhesion molecule-1 (ICAM-1) will decrease adhesion mediated by α4β1 and, to a lesser extent, α5β1. Similar inhibition is also seen when T cells are exposed to mAb 24, which stabilizes LFA-1 in an active state after triggering integrin function through divalent cation Mg2+, PdBu, or T cell receptor/ CD3 complex (TCR/CD3) cross-linking. Such cross talk decreases α4β1 integrin–mediated binding of T cells to fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In contrast, ligand occupancy or prolonged activation of β1 integrin has no effect on LFA-1 adhesion to ICAM-1. We also show that T cell migration across fibronectin, unlike adhesion, is mediated solely by α5β1, and is increased when the α4β1-mediated component of fibronectin adhesion is decreased either by cross talk or the use of α4-blocking mAb. The ability of mAb 24 Fab′ fragments to induce cross talk without cross-linking LFA-1 suggests signal transduction through the active integrin. These data provide the first direct evidence for cross talk between LFA-1 and β1 integrins on T cells. Together, these findings imply that activation of LFA-1 on the extravasating T cell will decrease the binding to VCAM-1 while enhancing the subsequent migration on fibronectin. This sequence of events provides a further level of complexity to the coordination of T cell integrins, whose sequential but overlapping roles are essential for transmigration.
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Smith, Andrew, Yolanda R. Carrasco, Paula Stanley, Nelly Kieffer, Facundo D. Batista, and Nancy Hogg. "A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes." Journal of Cell Biology 170, no. 1 (June 27, 2005): 141–51. http://dx.doi.org/10.1083/jcb.200412032.
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Cells such as fibroblasts and endothelial cells migrate through the coordinated responses of discrete integrin-containing focal adhesions and complexes. In contrast, little is known about the organization of integrins on the highly motile T lymphocyte. We have investigated the distribution, activity, and cytoskeletal linkage of the integrin lymphocyte function associated antigen-1 (LFA-1) on human T lymphocytes migrating on endothelial cells and on ligand intercellular adhesion molecule-1 (ICAM-1). The pattern of total LFA-1 varies from low expression in the lamellipodia to high expression in the uropod. However, high affinity, clustered LFA-1 is restricted to a mid-cell zone that remains stable over time and over a range of ICAM-1 densities. Talin is essential for the stability and formation of the LFA-1 zone. Disruption of the talin–integrin link leads to loss of zone integrity and a substantial decrease in speed of migration on ICAM-1. This adhesive structure, which differs from the previously described integrin-containing attachments displayed by many other cell types, we have termed the “focal zone.”
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Petruzzelli, L., L. Maduzia, and T. A. Springer. "Activation of lymphocyte function-associated molecule-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) mimicked by an antibody directed against CD18." Journal of Immunology 155, no. 2 (July 15, 1995): 854–66. http://dx.doi.org/10.4049/jimmunol.155.2.854.
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Abstract The beta 2-integrin (CD18) family members bind to their ligands subsequent to activation of a number of well defined and diverse signal transduction pathways. The precise molecular changes associated with activation of the integrin family members have remained elusive. Here, we characterize a monoclonal, CBR LFA-1/2, that binds to the beta 2-subunit and is able to mimic activation induced upon stimulation by phorbol esters. The Ab induces binding of the LFA-1-expressing cell line, JY, to ICAM-1 (CD54) and ICAM-3 (CD50). Activation of binding by this Ab is independent of Fc interactions and does not occur through cross-linking at the cell surface, because the Fab fragment of the Ab is able to modulate the same effect. Stimulation of neutrophils with CBR LFA-1/2 induces binding to ICAM-1 through activation of both LFA-1 and Mac-1. Activation of Mac-1 by CBR LFA-1/2 was further confirmed by stimulation of neutrophil binding to fibrinogen, a ligand for Mac-1. CBR LFA-1/2 lowers by 10-fold the concentration of Mg2+ required to achieve maximal binding of LFA-1 to ICAM-1. It therefore appears that CBR LFA-1/2 induces a conformational change that directly increases the avidity of beta 2-integrins for ligands.
Dissertations / Theses on the topic "Integrin LFA-1"
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Stewart, Mairi Purslow. "Activation of the leukocyte integrin LFA-1 lymphocytes." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321666.
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McDowall, Alison Jane. "Mechanisms of activation of the leukocyte integrin LFA-1." Thesis, Open University, 2000. http://oro.open.ac.uk/58066/.
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This work was undertaken to characterise the interaction of the leukocyterestricted integrin LFA-1 (CD1la/CD18) with its ligands. LFA-1 function is critical for an immune response and, for example, allows leukocyte binding and transmigration across the endothelium, antigen presentation and cytotoxic T lymphocyte-mediated killing. The ligands for LFA-1 are the Intercellular Adhesion Molecules (ICAMs), with ICAM-1, ICAM-2 and ICAM-3 being the best characterised. The binding sites on ICAM-1 and ICAM-3 for LFA-1 were investigated with the use of antibodies and mutated proteins. The following regions were found to have a role in binding LFA-1: the CFG face of ICAM-3 domain 1; domain 2 of ICAM-1; a residue in domain 1 of ICAM-1 that is mutated at high frequency in African populations and is associated with susceptibility to cerebral malaria. Binding of Mg2+ or Mn 2+ to the extracellular region of LFA-1 and intracellular signalling can both stimulate LFA-1 to adhere to ICAM-1, but by different processes. The former mechanism induces a high affinity form of LFA-1, which was shown to be achieved by an inter-domain movement involving the I domain of the LFA-1 a subunit. This is the first physical evidence for a conformational change occurring in an integrin upon activation. The mechanism by which intracellular signalling activates LFA-1 was demonstrated to involve calpaindependent clustering of LFA-1 in the membrane, thus increasing the avidity of LFA-1 for ICAM-1. Leukocyte Adhesion Deficiency-1 and Glanzmann's Thrombasthenia are genetic disorders in which mutations in the integrin genes result in absence of expression or expression of a non-functional integrin. The defects in function of leukocytes from a patient with clinical features of both disorders were studied. The results suggest that the patient has a novel form of integrin dysfunction in which integrins are expressed at normal levels, can be induced to bind their ligands by mechanisms which increase the affinity of interaction, but cannot be stimulated to bind ligand by intracellular signalling pathways.
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Stanley, Paula E. "The interaction between integrin LFA-1 and its ligand ICAM-1." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340738.
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Hedman, Håkan. "Regulation of leukocyte integrin adhesiveness." Doctoral thesis, Umeå universitet, Molekylärbiologi (Teknat- och Medfak), 1995. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100597.
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Parks, William. "Force activation of I domain containing and lacking integrins on live cells." Thesis, Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/42695.
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Cellular adhesion plays a crucial role in the biological function of cells, allowing them to communicate and signal, as well as physically anchor, by enabling them to adhere to either other cells or the extra cellular matrix (ECM). This process is regulated by several factors including intrinsic bond kinetics, internal cellular signaling, environment, force exerted on the bond, and force history of the bond. Concerning the force and force history dependence, the observation of catch bonds in integrin binding has asked as more questions than it has answered.
To explore the force and force history dependence this process, each bond was loaded to a peak force before relaxing to a much lower force that was held for the duration of the measurement. Two different integrins were studied, both of which have in previous works exhibited a catch bond. Furthermore, the effects of different metal ion conditions and an allosteric antagonist were also studied to elucidate the conformational effects on force priming of integrin. What was observed was that I domain, or αA domain, possessing integrin, whether tested against its more active or less active binding state, changed very little in terms of off rate once the priming force was applied. However in the I domain, or αA domain, lacking integrin, the observed off rate changed as well. It seems that force priming is capable of causing integrin to bind in a stronger manner regardless of the other conditions used to either activate or inhibit binding. However the way in which the binding is strengthened depends on the receptors structure.
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Geginat, Jens. "Interdependence between adhesion and proliferation the role of the [alpha]L- [alphaL-], [beta]2-integrin [beta2-integrin] (LFA-1) in t cell antigen receptor dependent proliferation of primary human t lymphocytes /." [S.l.] : [s.n.], 1999. http://www.diss.fu-berlin.de/1999/35/index.html.
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Sirim, Pinar. "Funktionelle Charakterisierung der Signaltransduktionskaskade des LFA-1-Integrins." Diss., lmu, 2001. http://nbn-resolving.de/urn:nbn:de:bvb:19-3716.
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Lam, Hang-yee Chloe, and 林倖而. "Identification of interacting partners of LFA-1 in the testis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/202255.
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Sweeney, Bernadette Mary. "Activation of LFA-1 through mutations within the IDAS site of the I Domain : their effects on ligand binding and the capacity of LFA-1 to signal to other integrins." Thesis, Open University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402826.
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Birkigt, Jessica [Verfasser], Eugen [Gutachter] Feist, and Ulrike [Gutachter] Seifert. "Die Rolle von SLP-76 bei der T-Zellrezeptor-vermittelten Aktivierung des Integrins LFA-1 in T-Zellen / Jessica Birkigt ; Gutachter: Eugen Feist, Ulrike Seifert." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2020. http://d-nb.info/1223615677/34.
Full textBook chapters on the topic "Integrin LFA-1"
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Yuki, Koichi. "Cell-Free Ligand-Binding Assays for Integrin LFA-1." In Integrin and Cell Adhesion Molecules, 73–78. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-166-6_6.
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Wiemer, Andrew J., Sarah Wernimont, and Anna Huttenlocher. "Live Imaging of LFA-1-Dependent T-Cell Motility and Stop Signals." In Integrin and Cell Adhesion Molecules, 191–204. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-166-6_13.
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Fischer, Alain. "Anti-LFA-1 Antibody as Immunosuppressive Reagent in Transplantation." In Integrins and ICAM-1 in Immune Responses, 89–97. Basel: KARGER, 1991. http://dx.doi.org/10.1159/000319058.
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Kaliannan, Jagatheesan, Anand Baskaran, and Nilanjan Dey. "Automatic Generation Control of Thermal-Thermal-Hydro Power Systems with PID Controller Using Ant Colony Optimization." In Renewable and Alternative Energy, 761–78. IGI Global, 2017. http://dx.doi.org/10.4018/978-1-5225-1671-2.ch023.
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In this work, Artificial Intelligence (AI) based Ant Colony Optimization (ACO) algorithm is proposed for Load Frequency Control (LFC) of interconnected multi–area hydrothermal power systems. Area 1&2 are thermal power systems and area 3 is a hydro power system, all the areas are interconnected through the appropriate tie-line. Thermal and hydro power plants are applied with reheat turbine and electric governor respectively. Investigated power system initially applied with conventional Proportional-Integral (PI) controller and controller parameters are optimized by using trial and error method considering Integral Time Absolute Error (ITAE) objective function. After that, the system is equipped with Proportional – Integral – Derivative (PID) controller and controller parameters are optimized by using ACO algorithm with ITAE objective function. The superiority of the proposed algorithm has been demonstrated by comparing conventional controller. Finally, The Simulation results of multi-area power system prove the effectiveness of the proposed optimization technique in LFC scheme and show its superiority over conventional PI controller.
Conference papers on the topic "Integrin LFA-1"
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Hojo, Kiminobu, Kentaro Yoshimoto, Ryuichi Yamamoto, Toshihiro Matsuoka, and Uwe Mayer. "Application of Master Curve Method to Fracture Toughness Estimation of the Transport and Storage Cask Material." In ASME 2008 Pressure Vessels and Piping Conference. ASMEDC, 2008. http://dx.doi.org/10.1115/pvp2008-61181.
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The transportation and storage casks have to be designed by considering transport and handling accidents. IAEA safety standard [1] requires drop test using a scale model and demonstration of structural integrity of the cask container vessel from the view point of leakage and instable fracture. For the fracture evaluation, it has to be verified that brittle fracture does not occur at the lowest temperature −40degC. MHI has developed the MSF-57BG cask whose body is made of forged low alloy steel LF3-m. It is well known that low alloy steel has the brittle-to-ductile transition temperature range of fracture toughness and large scatter of toughness value in this region. For the cask’s integrity evaluation, it is needed to obtain the fracture toughness dependent on temperature of this material by considering data scatter. The Master curve procedure [2] was proposed for estimation of fracture toughness of the pressure vessel on the basis of statistical procedure by using relatively small number of specimens. This paper examined the determination method of fracture toughness considering dynamic loading effect and data scatter in the brittle-to-ductile transition temperature by using the Master curve procedure.
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Fonseca, Nuno, Carlos Eduardo Siva de Sousa, and Petter Andreas Berthelsen. "Prediction of Heave and Pitch Low Frequency Wave Forces and Motions of a Semi-Submersible Floating Wind Turbine and Comparison With Model Test Data." In ASME 2022 4th International Offshore Wind Technical Conference. American Society of Mechanical Engineers, 2022. http://dx.doi.org/10.1115/iowtc2022-95009.
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Abstract Most of the floating wind turbine (FWT) sub-structure concepts are designed with long natural periods of the vertical motions to de-tune from the wave frequency range. The consequence is that the natural frequencies of heave, roll and pitch are excited by low frequency wave and wind loads. The paper focus is on the low frequency (LF) wave drift loads and the related heave and pitch responses of a semi-submersible type of FWT (12MW INO WINDMOOR). It presents several approaches to calculate the wave drift force coefficients and related forces in irregular waves, namely mean wave drift coefficients combined with Newman’s approximation, quadratic transfer functions (QTFs) neglecting the free surface integral from the 2nd order potential flow solution and QTFs based on the full 2nd order solution. The different approximations are used to perform nonlinear time domain simulations of the FWT motions and the results compared to the model test data (the model tests were performed in the ocean basin of SINTEF at a scale of 1:40). The LF damping of heave and pitch is represented by a linear and a quadratic damping coefficient identified from decay model tests. The coupled numerical solution requires a correct representation of the surge mode of motion. In this case, the wave drift forces are represented by empirical QTFs, while the LF damping includes a contribution from the calm water damping represented by a linear and a quadratic coefficient, together with a wave drift damping coefficient. The numerical results show a good agreement with the model test data in irregular waves when full QTFs are used to calculate the wave drift forces.
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Kiefner, John, Michael Rosenfeld, Peter Veloo, and Troy Rovella. "Estimating Toughness for LF and DC Welded ERW Seams." In 2020 13th International Pipeline Conference. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/ipc2020-9255.
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Abstract ERW pipe materials, particularly those manufactured prior to 1970, have exhibited higher rates of failures from seam manufacturing defects than other types of pipe materials. Typically, the seam bond line regions of low-frequency (LF) and direct-current (DC) welded ERW pipe materials exhibit poor resistance to manufacturing defects. The toughness of the bond line region is difficult to determine, and it is likely to vary from one piece of pipe to another. Pipeline operators must address the risk of ERW seam failures as part of their integrity management plans, but it is unlikely that they will know the toughness levels in the seams of their pipelines comprised of such materials. To avoid having to know the toughness levels in the seams, a pipeline operator can utilize a hydrostatic test to verify the integrity of a vintage ERW pipeline, but there are disadvantages the main one being that the pipeline must be taken out of service. Most likely an operator will choose to use an ILI crack tool to locate ERW seam anomalies to avoid having to take the pipeline out of service. Even if the seam defects can be located, correctly sized, and classified, however, the operator may have no idea of the effective toughness that is the key to deciding whether or not a given crack has to be excavated and repaired. Presented herein are two options for improving the effectiveness of an ILI integrity assessment of a pipeline with low toughness ERW seams. • Option 1 involves assuming a conservative level of toughness. Some such levels are available in the publicly available documents. Data from a large database of ERW seam failures are used to show the effectiveness of a fixed level of toughness at identifying critical defects while minimizing unnecessary digs. • Option 2 consists of first: back-calculating the toughness levels associated with the known crack sizes and failure pressures of the defects in the database of ERW seam failures, and second: calculating the probability that each type of defect would have been correctly identified at a particular level of confidence using a particular level of toughness. Using either of these options, a pipeline operator can improve the effectiveness of an ILI-crack-tool integrity assessment of a pipeline comprised of LF or DC welded ERW seams by reducing the number of unnecessary excavations while still being able to find the critical defects with an acceptable level of confidence.
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Tarantino, Mariano, Alessandro Del Nevo, Nicola Forgione, and Giacomino Bandini. "Post Test Analysis of ICE Tests." In 2012 20th International Conference on Nuclear Engineering and the ASME 2012 Power Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/icone20-power2012-54952.
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Since 1999 ENEA is developing the heavy liquid metal (HLM) technology aiming to support the design and implementation of a Lead cooled Fast Reactor (LFR) and an Accelerator Driven System (ADS), both in the frame of the Italian and European research programs. In these contexts several experiments have been performed, in different fields, going from coolant thermal-hydraulic, component development and structural material characterization. Recently, in the frame of the IP-EUROTRANS (6th Framework Program EU), domain DEMETRA, ENEA assumed the commitment to perform an integral experiment aiming to reproduce the primary flow path of a pool-type nuclear reactor, cooled by Lead Bismuth Eutectics (LBE). This experimental activity, named “Integral Circulation Experiment (ICE)”, has been implemented thanks a joint effort of several research institutes, mainly ENEA and University of Pisa, allowing to design an appropriate test section. This has been installed in the CIRCE facility, the largest worldwide experimental facility for the HLM technology investigation. The goal of the experiments was to demonstrate the technological feasibility of a heavy liquid metal (HLM) pooltype nuclear system in a relevant scale (1 MW), investigating the related thermal–hydraulic behavior under both steady state and transient conditions. This paper reports a description of the experiment, as well as the results carried out in the first experimental campaign run on the CIRCE pool, which consists of a full power steady state test, an un-protected loss of heat sink (ULOH) test, and an un-protected loss of flow (ULOF) test. The post-test analyses of the experiments is presented. The whole domain has been modeled by a suitable 1-D nodalization, and the results carried out have been studied performing numerical calculations by the REALP5 system code modified to take in account the LBE thermal-physical properties when employed as nuclear coolant. The obtained experimental results as well as the performed post-test analysis have demonstrated the thermal-hydraulic and technological feasibility of a pool-type nuclear system cooled by HLM.
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Tarantino, M., D. Martelli, I. Di Piazza, N. Forgione, P. Agostini, and G. Coccoluto. "HLM Fuel Pin Bundle Characterization in CIRCE Pool Facility." In 2014 22nd International Conference on Nuclear Engineering. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/icone22-30774.
Full textAbstract:
Since the Lead-cooled Fast Reactor (LFR) has been conceptualized in the frame of GEN IV International Forum (GIF), ENEA is strongly involved on the HLM technology development. Currently ENEA has implemented large competencies and capabilities in the field of HLM thermal-hydraulic, coolant technology, material for high temperature applications, corrosion and material protection, heat transfer and removal, component development and testing, remote maintenance, procedure definition and coolant handling. In this frame the Integral Circulation Experiment (ICE) test section has been installed into the CIRCE pool facility, and suitable experiments have been carried out aiming to deeply investigate the pool thermal-hydraulic behavior of a HLM cooled pool reactor. In particular a fuel pin bundle simulator (FPS) has been installed in the CIRCE pool. It has been conceived with a thermal power of about 1 MW and a linear power up to 25kW/m, relevant values for a LMFR. It consist of 37 fuel pins (electrically simulated) placed on a hexagonal lattice with a pitch to diameter ratio of 1.8. The pins have a diameter of 8.2mm and active lengths of 1 m. Along the FPS, three spacer grid properly designed by ENEA have been installed. The FPS has been deeply instrumented by several thermocouples. In particular three sections of the FPS have been instrumented to monitor the heat transfer coefficient along the bundle as well as the cladding temperature in different rank of sub-channels. A full characterization of the FPS has been experimentally achieved both under forced and natural circulation, and the main results gained during the run are reported into the paper. Moreover the paper reports a preliminary analysis and discussion of such results, also in comparison with CFD calculations performed by CFX code.
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Bagnoli, Kenneth, Thirumalai Neeraj, Greger Pioszak, Ryan Holloman, Gregory Thorwald, and Clifford Hay. "Fracture Toughness Evaluation of Pre-1980’s Electric Resistance Welded Pipeline Seam Welds." In 2022 14th International Pipeline Conference. American Society of Mechanical Engineers, 2022. http://dx.doi.org/10.1115/ipc2022-86014.
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Abstract In the 1950’s and 1960’s, economic expansion in Europe and North America led to significant growth in transmission pipeline capacity. Thus, many pipelines in operation today were constructed prior to 1980 and result in an aging pipeline infrastructure. An important mechanical integrity threat affecting oil and gas pipelines is the potential for fast fracture of longitudinal seam welds. A major factor affecting fast fracture resistance involves the welding practices used prior to 1980. The most common method was low-frequency electric resistance welding (LF-ERW). Imperfections were more prevalent using LF-ERW compared with modern high-frequency electric resistance welding (HF-ERW), employed for the last 40 years. Another important factor is the steel quality produced during this era. High tramp element levels, particularly sulfur, led to lower and more variable fracture toughness than steels produced after about 1980. To effectively manage the risk of fast fracture a strong statistical understanding of quasi-static fracture toughness in pipeline steels is important but has been lacking. To advance integrity management of existing pipeline systems, the fracture toughness of vintage pipeline materials has been characterized by conducting 550 fracture toughness tests, collecting data from literature sources (25) [1] [2], and test results supplied from a secondary pipeline operator (45), for a total dataset of 620. The testing program included a wide range of manufacturers and fabrication years based on sampling over 30 individual pipelines. The results suggest that it is possible to treat pre-1980 pipeline steels/welds as a single cohort. This is valuable since toughness data for individual pipelines are often insufficient or not available. The test data was analyzed to provide input for either a deterministic or probabilistic analysis. Consideration for the constraint effects of specimen geometry was also investigated to address the transferability of test results to an axially oriented flaw in a thin walled 0.2–0.4in (5–10 mm) pipeline. Constraint was characterized by using J-Q and J-A2 theory in a 3D FE simulation. Finally, analysis of the weld microstructure provided fundamental insight into the operative fracture mechanisms responsible for their toughness properties.
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Phillips, David R., Laurence A. Fitzgerald, Leslie V. Parise, and Israel F. Charo. "The Platelet Membrane Glycoprotein IIb-III a Complex: Member of a Superfamily of Adhesive Protein Receptors." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643727.
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The glycoprotein (GP) IIb-IIIa complex isthe receptor for fibrinogen,fibronectin and von Willebrand factor on the surface of activated platelets that mediates platelet aggregation.The GP IIb-IIIa complex contains two subunits; an a subunit, GP IIb, and a smaller 8 subunit, GP IIIa. To identify the subunits of GP IIb-IIIa responsible for fibrinogen binding, we examined the ability of purified subunitsto bind to immobilized fibrinogen. Both the GP IIb and the GP III a subunits have fibrinogen binding activity, suggesting that fibrinogen binds to multiple sites onthe GP I Ib-IIIa complex.A GP Ilb-IIIa-like complex has been identified on endothelial cells which is immunoreactive with antibodies raised against platelet GP IIb-III a. This complex binds a similar broadspectrum of adhesive proteins as plateletGP IIb-IIIa and appears to mediate the attachment of endothelial cells to the extracellular matrix. We have established, however, that while GP Ilia in endothelial cells is the same primary translation product as platelet GP Ilia, the endothelialcell "GP lib" is a different, but closely related, protein from platelet GP lib. This close relationship of the receptors on these two cells is reflective of recent observations in several laboratories which have shown that a wide variety of cells contain surface glycoproteins which have structural and functionalsimilarities to the GP IIb-IIIa complexinplatelets and the "GP IIb-IIIa-like" complex in endothelial cells.These glycoproteins, which have been termed "integrins" or "cytoadhesins", are complexes of highly homologous a and 8 subunits, mediate cell-cell or cel 1-substrata interactions, and may also bind the RGD sequence on adhesive proteins. Although in vertebrates this family includes at least ten receptor complexes, there are only three known 8 subunits, each of which defines a subset of receptors. One is GP IIIa, the 8 subunit for GP IIb-IIIa and the vitronectin receptor; another is the 8 subunit for the fibronectin receptors and the very late antigens on lymphocytes; the third is the 8subunit of the Mac-1, LFA-1, and P150/95 antigens on leukocytes. These three 6 subunits have been cloned and sequenced. Each contains 746-777 amino acids, a singletransmembrane domain near the carboxy terminus, 56 cysteines in identical positionsof the proteins, 31 of which are clustered into four repeats, and an overall identity in 45-47% of their amino acids. The asubunits are more diverse in size but appear to have a similar degree of homology.The available sequence information indicates that they contain a single transmembrane domain near their carbody terminii and four tandem repeats near their amino terminii which include sequences indicativeof four Ca2+-binding sites. These may account for the known Ca2+-binding properties of GP IIb. GP I Ib-IIIa and the other adhesive protein receptors therefore appear to have two membrane insertion sites, one on each subunit,with short cytoplasmic domains derived from the carboxy terminii of the two subunits. The amino terminii along with most ofthe mass of these proteins is extracellular. It can be anticipated that the highlyhomologous sequences between GP IIb-IIIa and the other adhesive protein receptors will help identify the functional domainswhich have been conserved since their evolutionary divergences.
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Korol, Kaitlyn, Yvan Hubert, Gordon Fredine, Petra Senf, and Sherry-Ann Koon Koon. "A Study of Crack Detection Ultrasonic Attributes to Manage Leak Threats Associated With Short Crack-Like Flaws in ERW Pipelines." In 2016 11th International Pipeline Conference. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/ipc2016-64583.
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Inline Inspection (ILI) tools along with hydrostatic testing have been the primary identification and mitigation techniques for cracking threats on liquids pipelines. Each technique faces detection challenges in relation with the weld type, geometry, and feature types, sizes and orientations. Low frequency electric resistance welds (LF ERWs) are subject to a number of crack-like defects due to the ERW manufacturing process. These defects may include fatigue cracks, lack of fusion, burned metal defects, stitched welds, cold welds, cracks in hard HAZ, surface breaking hook cracks near the weld and selective seam corrosion [1]. Within a population of features in a pipeline, a subpopulation can exist of short, deep defects (>50% wt) that may be undersized by the ILI tool or not detected by a hydrostatic test due to the length of the flaw. For ILI tools, a length detection threshold is set based on the tool speed (which is dictated by the tool type and configuration). A feature may be undersized by the ILI tool if its length is below this tool threshold. For hydrostatic testing, through-wall flaws may be undetected if the flaw length is below the critical length for a significant leak. Through detailed ILI data analysis, Enbridge along with PII Pipeline Solutions has been able to consistently identify short and deep crack-related defects on LF ERW pipe through means other than feature dimensions provided by the ILI tool. In-ditch non-destructive examination and destructive laboratory testing has confirmed these features are critical and fall below current ILI tool’s detection thresholds. This paper discusses unique ILI data attributes that may identify a more severe feature than would conventional ILI sizing practices, and how the identification and selection procedure is being applied across Enbridge’s pipeline system. This analysis effort aligns with Enbridge’s goal to continuously improve its integrity management processes and further enhance the safety of its pipelines.
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Martelli, D., M. Tarantino, and I. Di Piazza. "Experimental Activity for the Investigation of Mixing and Thermal Stratification Phenomena in the CIRCE Pool Facility." In 2016 24th International Conference on Nuclear Engineering. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/icone24-60920.
Full textAbstract:
Since the Lead-cooled Fast Reactor (LFR) has been conceptualized in the frame of GEN IV International Forum (GIF), ENEA is strongly involved in the HLM technology development. In particular, several experimental campaign employing HLM loop and pool facilities (CIRCE [1], NACIE [2], HELENA [3], HERO [4]) are carried out in order to support HLM technologies development. In this frame, suitable experiments were carried out on the CIRCE pool facility refurbished with the Integral Circulation Experiment (ICE) test section in order to investigate the thermal hydraulics and the heat transfer in grid spaced Fuel Pin Bundle cooled by liquid metal providing, among the others aim, experimental data in support of codes validation for the European fast reactor development. The study of thermal stratification in large pool reactor is relevant in the design of HLM nuclear reactor especially for safety issue. Thermal stratification should induce thermomechanical stresses on the structures and in accidental scenario conditions, could opposes to the establishment of natural circulation which is a fundamental aspect for the achievements of safety goals required in the GEN-IV roadmap. In the present work, a Protected Loss of Heat Sink with Loss Of Flow (PLOHS+LOF) scenario is experimentally simulated and the mixed convection with thermal stratification phenomena is investigated during the simulated transient, as foreseen in the frame of Horizon 2020 SESAME project [5]. A full characterization of thermal stratification inside the pool is presented, and the main results gained during the run are reported. The two tests named A (20 h) and B (6 h) here reported, essentially differs for the power supplied to the fuel bundle during the full power run (800 kW and 600 kW respectively). After the transition to natural circulation conditions, the power supplied to the bundle is decreased to about 30 kW simulating the decay heat. Finally the Nusselt number for the central subchannel of the fuel bundle simulator (FPS) is evaluated and compared with values obtained from Ushakov and Mikityuk correlations [6–7].
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Ma, Jing, Michael Rosenfeld, Peter Veloo, Troy Rovella, and Peter Martin. "An Approach to Engineering Critical Assessment of Assets That Cannot Be Inline Inspected." In 2018 12th International Pipeline Conference. American Society of Mechanical Engineers, 2018. http://dx.doi.org/10.1115/ipc2018-78132.
Full textAbstract:
Hydrostatic pressure testing is the most widely accepted approach to verify the integrity of assets used for the transportation of natural gas. It is required by Federal Regulations 49 CFR §192 to substantiate the intended maximum allowable operating pressure (MAOP) of new gas transmission pipelines. The Pipeline and Hazardous Materials Safety Administration (PHMSA) Notice of Proposed Rulemaking (NPRM) with Docket No. PHMSA-2011-0023 [1], proposes an additional requirement for MAOP verification of existing pipelines that: i) do not have reliable, traceable, verifiable, or complete records of a pressure test; or ii) were grandfathered into present service via 49 CFR §192.619(c). To meet this requirement, the NPRM proposes that an Engineering Critical Assessment (ECA) can be considered as an alternative to pressure testing if the operator establishes and develops an inline inspection (ILI) program. The ECA must analyze cracks or crack-like defects remaining or that could remain in the pipe, and must perform both predicted failure pressure (PFP) and crack growth calculations using established fracture mechanics techniques. For assets that cannot be assessed by ILI, however, the implementation of an ECA is hindered by the lack of defect size information. This work documents a statistical approach to determine the most probable PFP and remaining life for assets that cannot be assessed by ILI. The first step is to infer a distribution of initial defect size accumulated through multiple ILI and in-ditch programs. The initial defect size distribution is established according to the as-identified seam type, e.g. low-frequency electric resistance weld (LF-ERW), high-frequency electric resistance weld (HF-ERW), flash weld (FW), single submerged arc weld (SSAW), or seamless (SMLS). The second step is to perform fracture mechanics assessment to generate a probabilistic distribution of PFPs for the asset. In conjunction with the defect size distribution, inputs into the calculation also include the variations of mechanical strength and toughness properties informed by the operator’s materials verification program. Corresponding to a target reliability level, a nominal PFP is selected through its statistical distribution. Subsequently applying the appropriate class location factor to the nominal PFP gives the operator a basis to verify their current MAOP. The last step is to perform probabilistic fatigue life calculations to derive the remaining life distribution, which drives reassessment intervals and integrity management decisions for the asset. This paper will present some case studies as a demonstration of the methodology developed and details of calculation and establishment of database.