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To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection. 相似文献
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This research derives and tests hypotheses from two alternative conceptual models: the modified extended family model, and the changing family constraints model, which takes into account recent changes in work and family life. The hypotheses address social class differences in geographic distance and contact frequency between middle-aged children and their parents over time. Simultaneous probit models are used to analyze distance and contact as jointly determined outcomes with data from the USC Longitudinal Study of Generations and Mental Health. Results from these analyses indicate that children's 1971 educational aspirations and social class positions predict 1991 distance and contact between generations. Parents who have lower 1991 incomes, however, live farther from children and talk with them on the telephone less frequently than higher-income parents. Thus, the effects of early social class position support the modified extended family model, whereas the effects of current social class position support the changing family constraints model. 相似文献
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VL Shnyrov GG Zhadan C Cobaleda A Sagrera I Mu?oz-Barroso E Villar 《Canadian Metallurgical Quarterly》1997,341(1):89-97
The spatial and temporal pattern of expression of enhancer trap lines reporting on the wingless (wg) and engrailed (en) genes was characterized in the adult antenna of Drosophila melanogaster. The time courses of expression seen for wg and en, although different from each other, reveal a complex well-controlled pattern of temporal expression, providing evidence that regulatory mechanisms are preserved throughout the life span of the adult fly. Altering the life span demonstrates that the temporal patterns of expression of both wg and en are linked to life span. These studies suggest that the expression of wg and en in the adult antenna is controlled by age-dependent mechanisms. 相似文献
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T Goldman AL Hallin CM Hoffman LE Piilonen D Preston RD Bolton MD Cooper JS Frank PA Heusi GE Hogan FG Mariam HS Matis RE Mischke VD Sandberg GH Sanders U Sennhauser R Werbeck RA Williams D Grosnick SC Wright SL Wilson R Hofstadter EB Hughes MW Ritter VL Highland J McDonough 《Canadian Metallurgical Quarterly》1987,36(5):1543-1546
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Gag rules-clauses in managed care contracts that prevent physicians from disclosing information that the plan may find disparaging, but that could relate directly to the patient's health-have recently been the subject of ethical condemnation and legislative prohibition. Another serious problem in managed care contracts, trade secrets, or guidelines and quality assurance mechanisms that are imposed on physicians while their origins are shrouded in proprietary secrecy, have by contrast received little attention. Responses to these ethical challenges to the physician's integrity must involve individual physicians, managed care organizations, professional organizations, and public policymakers. 相似文献
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Engineered heterostructures create new functionality by integrating dissimilar materials. Combining different 2D crystals naturally produces two distinct classes of heterostructures, vertical van der Waals (vdW) stacks or 2D sheets bonded laterally by covalent line interfaces. When joining thicker layered crystals, the arising structural and topological conflicts can result in more complex geometries. Phase separation during one‐pot synthesis of layered tin chalcogenides spontaneously creates core–shell structures in which large orthorhombic SnS crystals are enclosed in a wrap‐around shell of trigonal SnS2, forcing the coexistence of parallel vdW layering along with unconventional, orthogonally layered core–shell interfaces. Measurements of the optoelectronic properties establish anisotropic carrier separation near type II core–shell interfaces and extended long‐wavelength light harvesting via spatially indirect interfacial absorption, making multifunctional layered core–shell structures attractive for energy‐conversion applications. 相似文献