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The CCL15 is a human CC chemokine that activates the receptors, CCR1 and CCR3. Unlike other chemokines, it contains an unusually long N-terminal domain of 31 amino acids preceding the first cysteine residue and a third disulfide bond. To elucidate the functional role of distinct structural determinants, a series of sequential amino-terminal truncated and point-mutated CCL15 derivatives as well as mutants lacking the third disulfide bond and the carboxy-terminal α-helix were synthesized using 9-fluorenylmethoxycarbonyl (Fmoc) chemistry. We demonstrate that a truncation of 24 amino acid residues (Δ24-CCL15) converts the slightly active 92-residue Δ0-CCL15 into a potent agonist of CC chemokine receptor 1 (CCR1) and a weak agonist of CCR3 in cell-based assays. The biological activity decreases from Δ24-CCL15 to Δ29-CCL15, and re-increases from Δ29-CCL15 to Δ30-CCL15. Thus, an exocyclic N-terminal region of only one amino acid residue is sufficient for efficient CCR1 activation. As none of the peptides investigated except for Δ24-CCL15 activates CCR3, we suggest that CCR1 is the major receptor for CCL15 in vivo. Further we demonstrate that the third disulfide bond of CCL15 and an exchange of tyrosine in position 70 by a leucine residue, which is conserved in CXC chemokines, do not alter the interaction with CCR1. In contrast, a CCL15 derivative lacking the carboxy-terminal α-helix exhibits a complete loss of tertiary structure and hence loss of CCR1 agonistic and binding activity. This study demonstrates that specific protein residues in chemokines, which contribute to receptor–ligand interaction, vary significantly between chemokines and cannot be extrapolated using data from functionally related chemokines. [ABSTRACT FROM AUTHOR]

Efficiency is a basic issue in Data Envelopment Analysis (DEA). There are different types of efficiency in DEA, e.g. Technical Efficiency (TE), Cost Efficiency (CE) and Revenue Efficiency (RE). They may be different in terms of efficiency score values because they use different information obtained from Decision Making Units (DMUs). One of these efficiency types (TE) uses only input and output quantities, another (CE) uses input, output and input cost vectors and still another (RE) uses input, output and output benefit vectors. In real problems, not the cost of each input or the benefit of each output is usually known and accessible, and just the costs (benefits) of some inputs (outputs) of each DMU are known. In this paper, we suggest a method and models to measure the efficiency of DMUs when some input costs and some output benefits are known. The proposed measure is a generalization of TE, CE and RE. This measure is very useful to evaluate the performance of DMUs and uses more information than the other measures. We show that the CCR model to evaluate TE and the minimal cost model to evaluate CE are special cases of the proposed model. Finally we present three examples to compare the proposed measure of efficiency with the other measures of efficiency. [ABSTRACT FROM AUTHOR]