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- Soffel, M., et al.
(författare)
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The IAU 2000 Resolutions for Astrometry, Celestial Mechanics, and Metrology in the Relativistic Framework: Explanatory Supplement
- 2003
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X. ; 126:6, s. 2687-2706
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the IAU resolutions B1.3, B1.4, B1.5, and B1.9 that wereadopted during the 24th General Assembly in Manchester, 2000, andprovides details on and explanations for these resolutions. It isexplained why they present significant progress over the correspondingIAU 1991 resolutions and why they are necessary in the light of presentaccuracies in astrometry, celestial mechanics, and metrology. In fact,most of these resolutions are consistent with astronomical models andsoftware already in use. The metric tensors and gravitational potentialsof both the Barycentric Celestial Reference System and the GeocentricCelestial Reference System are defined and discussed. The necessity andrelevance of the two celestial reference systems are explained. Thetransformations of coordinates and gravitational potentials arediscussed. Potential coefficients parameterizing the post-Newtoniangravitational potentials are expounded. Simplified versions of the timetransformations suitable for modern clock accuracies are elucidated.Various approximations used in the resolutions are explicated andjustified. Some models (e.g., for higher spin moments) that serve thepurpose of estimating orders of magnitude have actually never beenpublished before.
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| 2. |
- Kahn, J, et al.
(författare)
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Overexpression of CXCR4 on human CD34(+) progenitors increases their proliferation, migration, and NOD/SCID repopulation
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 103:8, s. 2942-2949
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Tidskriftsartikel (refereegranskat)abstract
- A major limitation to clinical stem cell-mediated gene therapy protocols is the low levels of engraftment by transduced progenitors. We report that CXCR4 overexpression on human CD34(+) progenitors using a lentiviral gene transfer technique helped navigate these cells to the murine bone marrow and spleen in response to stromal-derived factor 1 (SDF-1) signaling. Cells overexpressing CXCR4 exhibited significant increases in SDF-1-mediated chemotaxis and actin polymerization compared with control cells. A major advantage of CXCR4 overexpression was demonstrated by the ability of transduced CD34(+) cells to respond to lower, physiologic levels of SDF-1 when compared to control cells, leading to improved SDIF-1-induced migration and proliferation/survival, and finally resulting in significantly higher levels of in vivo repopulation of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice including primitive CD34(+)/CD38(-/low) cells. Importantly, no cellular transformation was observed following transduction with the CXCR4 vector. Unexpectedly, we documented lack of receptor internalization in response to high levels of SDF-1, which can also contribute to increased migration and proliferation by the transduced CD34(+) cells. Our results suggest CXCR4 overexpression for improved definitive human stem cell motility, retention, and multilineage repopulation, which could be beneficial for in vivo navigation and expansion of hematopoietic progenitors.
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| 7. |
- Marcos, Nuno T., et al.
(författare)
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Role of the Human ST6GalNAc-I and ST6GalNAc-II in the Synthesis of the Cancer-Associated Sialyl-Tn Antigen
- 2004
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Ingår i: CANCER RESEARCH. - 0008-5472. ; 64:19, s. 7050-7
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Tidskriftsartikel (refereegranskat)abstract
- The Sialyl-Tn antigen (Neu5Acalpha2-6GaINAc-O-Ser/Thr) is highly expressed in several human carcinomas and is associated with carcinoma aggressiveness and poor prognosis. We characterized two human sialyltransferases,(CMP)-C-.-Neu5Ac:GaINAc-R alpha2,6-sialyltransferase (ST6GaINAc)-I and ST6GaINAc-II, that are candidate enzymes for Sialyl-Tn synthases. We expressed soluble recombinant hST6GaINAc-I and hST6GaINAc-II and characterized the substrate specificity of both enzymes toward a panel of glycopeptides, glycoproteins, and other synthetic glycoconjugates. The recombinant ST6GaINAc-I and ST6GaINAc-II showed similar substrate specificity toward glycoproteins and GaINAcalpha-O-Ser/Thr glycopeptides, such as glycopeptides derived from the MUC2 mucin and the HIVgp120. We also observed that the amino acid sequence of the acceptor glycopeptide contributes to the in vitro substrate specificity of both enzymes. We additionally established a gastric cell line, MKN45, stably transfected with the full length of either ST6GaINAc-I or ST6GaINAc-II and evaluated the carbohydrate antigens expression profile induced by each enzyme. MKN45 transfected with ST6GaINAc-I showed high expression of Sialyl-Tn, whereas MKN45 transfected with ST6GaINAc-II showed the biosynthesis of the Sialyl-6T structure [GaIbeta1-3 (Neu5Acalpha2-6)GaINAc-O-Ser/Thr].In conclusion, although both enzymes show similar in vitro activities when Tn antigen alone is available, whenever both Tn and T antigens are present, ST6GaINAc-I acts preferentially on Tn antigen, whereas the ST6GaINAc-II acts preferentially on T antigen. Our results show that ST6GaINAc-I is the major Sialyl-Tn synthase and strongly support the hypothesis that the expression of the Sialyl-Tn antigen in cancer cells is due to ST6GaINAc-I activity.
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