Linker

This paper describes, in synchrony, the use, form, and position of the linking devices with ka in coordinating phrases and clauses and in subordinate clauses. This study also explores the relation between the different occurrences of ka and investigates a diachronic common source. Taking into account such parameters as weight, cohesion, and variability (Lehmann 2002), I advance the hypothesis that there have been two routes of grammaticalization. These two routes include the free coordinator ka which has given rise to a dependent marker-ka that forms subordinators, and the subjunctive mood-ka which seems to be the grammaticalization of the assertive mood marker-ka used for speech-act participants.

Abstract
Aim. Polyamidoamine (PAMAM) dendrimers inherent properties have made it the nanocarrier of choice in the current era of innovation. Dendrimer based products are growing and mushrooming like anything in the current time. Although it suffer from hemolytic toxicity which could be reduced by protecting free amino group. Methods. In the present work alternate acetylated method for PAMAM dendrimers was discussed. 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide Linker was used for acetylation. The acetylated conjugate
was evaluated for color reaction, Ultraviolet–visible spectroscopy, Fourier Transform infrared spectroscopy,
Differential scanning calorimetric, Nuclear magnetic resonance spectra studies. Results. The PAMAM dendrimers were synthesized using divergent approach and further acetylated.
Change in λmax values from 282.0 to 282.5 nm was observed for acetylated dendrimers. Characteristic peak of N-H stretch of primary amine at 3284.16 cm-1 was disappeared due to conversion of primaryamine to secondary amine. A new peak of –(CO)-NH stretch was obtained at 1640.28 cm-1 (medium) which shows attachment of acetic acid surface group. The changes in Endothermic peak from 120.56 to 110.400C were observed which shows the PAMAM dendrimers surface modifications The peak of –NH2 at 2.99 ppm was replaced by (–NHCOCH3) at 2.42 ppm further supports the proof of acetylation. Conclusions. The spectral data clearly revealed that this approach for acetylation gives considerable amount of acetylation in less time duration with elimination of organic solvent. This method could be employed for regular acetylation of amine terminated nanocarriers. EDC linker mediated capping of amine groups opened a new avenue for acetylation of amine terminated protein/peptides. Keywords: Dendrimers, Polyamidoamine (PAMAM), Etylenediamine, Acetylation, Linker, Surface Properties.

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [64Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (64Cu). The decay of 64Cu produces numerous low-energy electrons, enabling the 64Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA. Accordingly, the in vitro internalization kinetic and the cytotoxic activity of [64Cu]Cu-NOTA-C3-TP and its derivatives were investigated with colorectal cancer (HCT116) and normal human fibroblast (GM05757) cells. Radiolabeling by 64Cu results in a >55,000-fold increase of cytotoxic potential relative to [NatCu]Cu-NOTA-C3-TP at 72 h post administration, indicating a large additive effect between 64Cu a...