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Several analogs exhibited more potent cytotoxicity against HeLa cells compared to 381, including those containing meta -halogenation in the supplied 382 mimics

However, after direct injection of folic acid or FR-binding peptide into the hippocampus of aged mice, FRs were detected within neuronal nuclei [16], demonstrating that FR can be expressed in differentiated neurons themselves

These compounds have been also tested in two now completed phase-II and -III trials for the treatment of systemic lupus erythematosus [310] and diabetes mellitus type 1 [311] respectively, showing progressive improvement in disease activity thereby opening the way for new treatment perspectives

However, technology also enables valuable social support and maintains relationships that might otherwise be lost due to geographic or physical barriers