Multifunctional gadolinium-based dendritic macromolecules as liver targeting imaging probes.
ABSTRACT The quest for highly efficient and safe contrast agents has become the key factor for successful application of magnetic resonance imaging (MRI). The gadolinium (Gd) based dendritic macromolecules, with precise and tunable nanoscopic sizes, are excellent candidates as multivalent MRI probes. In this paper, a novel series of Gd-based multifunctional peptide dendritic probes (generation 2, 3, and 4) possessing highly controlled structures and single molecular weight were designed and prepared as liver MRI probes. These macromolecular Gd-ligand agents exhibited up to 3-fold increase in T(1) relaxivity comparing to Gd-DTPA complexes. No obvious in vitro cytotoxicity was observed from the measured concentrations. These dendritic probes were further functionalized with multiple galactosyl moieties and led to much higher cell uptake in vitro as demonstrated in T(1)-weighted scans. During in vivo animal studies, the probes provided better signal intensity (SI) enhancement in mouse liver, especially at 60 min post-injection, with the most efficient enhancement from the galactosyl moiety decorated third generation dendrimer. The imaging results were verified with analysis of Gd content in liver tissues. The design strategy of multifunctional Gd-ligand peptide dendritic macromolecules in this study may be used for developing other sensitive MRI probes with targeting capability.
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Article: Agree and Epp in Bantu[show abstract] [hide abstract]
ABSTRACT: C agrees in the -features of an operator in its Spec but not one in situ in many Bantu languages. Despite this I argue that a closest c-command based account (Chomsky 2000) is superior to a Spec–head agreement analysis, for two reasons. First, feature-valuation under closest c-command permits a unified treatment of Bantu operator agreement and West Germanic complementizer agreement with subjects. Second, it explains a common requirement that subjects be in situin Bantu A-movement constructions: a subject raised to Spec, TP would intervene between Cs -features and the operator in outer Spec, vP that must value them. Like wh-movement, subject raising always coincides with agreement in Bantu; I propose that Bantu uninterpretable -features have EPP features. These are distinct from the classical EPP of T which, I argue, underlies a verbal agreement requirement giving every Bantu inflectional category a specifier. I show that nominative Case-checking is independent of both agreement and EPP in Bantu.Natural Language and Linguistic Theory 01/2005; 23(2):219-279. · 0.76 Impact Factor