Overview
On this page we provide selected citations for each application.
Biodistribution
Journal articles
- Bugelski, P.J. et al. CNTO 530: Molecular Pharmacology in Human UT-7EPO Cells and Pharmacokinetics and Pharmacodynamics in Mice. J Biotechnol 134, 171-180 (2008).
- DeFrees, S. et al. GlycoPEGylation of Recombinant Therapeutic Protein Produced in Eschericia coli. Glycobiology 16, 833-843 (2006).
- Ivey, N.S., Martin, J., Scheld, W.M., & Nathan, B.R. A New Method for Measuring Blood-Brain Barrier Permeability Demonstrated with Europium-Bound Albumin During Experimental Lipopolysaccharide (LPS) Induced Meningitis in the Rat. J of Neurosci Meth 142, 91-95 (2005).
- Hale, S.L., Daí, W., Dow, J.S., Kloner, R.A. Mesenchymal Stem Cell Administration at Coronary Artery Reperfusion in the Rat by Two Delivery Routes: A Quantitative Assessment. Life Sci 83, 511-515 (2008).
- Mignet, N. et al. Liposome Biodistribution by Time Resolved Fluorimetry of Lipophilic Europium Complexes. Eur Biophys J 35, 155-161 (2006).
- Neville, M.E. et al. A Comparison of Biodistribution of Liposomal and Soluble IL-2 by a New Method Based on Time-Resolved Fluorometry of Europium. Cytokine 12, 1702-1711 (2000).
Biomolecular interaction
(protein-protein interaction, protein-peptide interaction, etc.)
Journal articles
- Sato, A., Kumagai, T., Aoki, J. & Ebina, K. Synthetic biotinylated peptide compounds derived from Asp-hemolysin: Novel potent inhibitors of platelet-activating factor. European journal of pharmacology (2012).
- Kwok, W. W. et al. Frequency of Epie-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire. Journal of Immunology (Baltimore, Md.: 1950) (2012)
- De, S.K. et al. Design, Synthesis, and Structure−Activity Relationship of Substrate Competitive, Selective, and in Vivo Active Triazole and Thiadiazole Inhibitors of the c-Jun N-Terminal Kinase. J Med Chem 52, 1943-1952 (2009).
- Delerive, P. et al. PGC-1 Functions as a Transcriptional Coactivator for the Retinoid X Receptors. J Biol Chem 277, 3913-3917 (2002).
- Glickman, J.F. et al. A Comparison of ALPHAScreen, TR-FRET, and TRF as Assay Methods for FXR Nuclear Receptors. J Biomol Screen 7, 3-10 (2002).
- Kadkhodayan, S. et al. Evaluation of Assay Technologies for the Identification of Protein-Peptide Interaction Antagonists. Assay Drug Dev Technol 5, 501-513 (2007).
- Rega, M.F., Reed, J.C. & Pellecchia, M. Robust Lanthanide-Based Assays for the Detection of Anti-Apoptotic Bcl-2-Family Protein Antagonists. Bioorg Chem 35, 113-120 (2007).
- Stebbins, J.L. et al. Identification of a New JNK Inhibitor Targeting the JNK-JIP Interaction Site. Proc Natl Acad Sci U S A. 105, 16809--16813 (2008).
Revvity technical publications
- Hurskainen, P., Frang, H., Vikstrom, S., Karvinen, J. & Hemmila, I. Heterogeneous and Homogeneous Time-resolved Fluorescence-Based Assays for a Low-Affinity Binding Reaction. Revvity Poster.
Cell cytotoxicity kit
Journal articles
- Murakami, Y. et al. Toso, a functional IgM receptor, is regulated by IL-2 in T and NK cells. J. Immunol. 189, 587–597 (2012).
- Chen, H.-M. et al. Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine. Cancer immunology, immunotherapy: CII (2012).
- Miller, A. S., Tejada, M. L. & Gazzano-Santoro, H. Development of an ELISA based bridging assay as a surrogate measure of ADCC. Journal of Immunological Methods (2012).
- Amann, M. et al. Therapeutic Window of an EpCAM/CD3-Specific BiTE Antibody in Mice is Determined by a Subpopulation of EpCAM-Expressing Lymphocytes that is Absent in Humans. Cancer Immunol Immun 58, 95-109 (2009).
- Conaghan, P. et al. Targeted Killing of Colorectal Cancer Cell Lines by a Humanised IgG1 Monoclonal Antibody that Binds to Membrane-Bound Carcinoembryonic Antigen. Br J Cancer 98, 1217-1225 (2008).
- Poggi, A. et al. Effective in Vivo Induction of NKG2D Ligands in Acute Myeloid Leukaemias by All-Trans-Retinoic Acid or Sodium Valproate. Leukemia 23, 641-648 (2009).
- Weber, G. et al. WT1 Peptide-Specific T Cells Generated from Peripheral Blood of Healthy Donors: Possible Implications for Adoptive Immunotherapy After Allogeneic Stem Cell Transplantation. Leukemia 23, 1634-1642 (2009).
Revvity technical publications
- Sippola, K. et al. Cell Based Assay for Studying the Effects of Cytotoxic Agents. Revvity Poster.
- Vikstrom, S., Lahde, T. & Blomberg, K. Technical Tips for the Cell Cytotoxicity Assay using the DELFIA Technology. Revvity Application Note.
- A new simplified, gentle cell-labelling method for non-radioactive cytotoxicity assays. Revvity Application Note.
Cell proliferation kit
Journal articles
- Wu, T. et al. Immunosuppressive drugs on inducing Ag-specific CD4(+)CD25(+)Foxp3(+) Treg cells during immune response in vivo. Transpl. Immunol. 27, 30–38 (2012).
- Malaguarnera, R. et al. Proinsulin Binds with High Affinity the Insulin Receptor Isoform A and Predominantly Activates the Mitogenic Pathway. Endocrinology (2012).Brillard, E. et al. Natural Killer Cells Prevent CD28-Mediated Foxp3 Transcription in CD4+CD25- T Lymphocytes. Exp Hematol 35, 416-425 (2007).
- Brunati, A.M. et al. Cross-Talk Between PDGF and S1P Signalling Elucidates the Inhibitory Effect and Potential Antifibrotic Action of the Immunomodulator FTY720 in Activated HSC-Cultures. Biochimica Biophysica Acta 1783, 347-359 (2008).
- Hoo, W.S. et al. Vaccination with Cell Immunoglobulin Mucin-1 Antibodies and Inactivated Influenza Enhances Vaccine-Specific Lymphocyte Proliferation, Interferon-γ Production and Cross-Strain Reactivity. Clin Exp Immunol 145, 123--129 (2006).
- Koslowski, M. et al. MS4A12 Is a Colon-Selective Store-Operated Calcium Channel Promoting Malignant Cell Processes. Cancer Res 68, 3458-3466 (2008).
- Liu, Z. & Habener, J.F. Glucagon-Like Peptide-1 Activation of TCF7L2-Dependent Wnt Signaling Enhances Pancreatic Beta Cell Proliferation. J Biol Chem 283, 8723-8735 (2008).
- Pallandre, J. et al. Role of STAT3 in CD4+CD25+FOXP3+ Regulatory Lymphocyte Generation: Implications in Graft-versus-Host Disease and Antitumor Immunity. J Immunol 179, 7593-7604 (2007).
- Selmani, Z. et al. Human Leukocyte Antigen-G5 Secretion by Human Mesenchymal Stem Cells Is Required to Suppress T Lymphocyte and Natural Killer Function and to Induce CD4+CD25highFOXP3+ Regulatory T Cells. Stem Cells 26, 212-222 (2008).
- Villa, A.M. et al. Choline and Phosphatidylcholine Fluorescent Derivatives Localization in Varcinoma Vells Dtudied by Laser Scanning Confocal Fluorescence Microscopy. Eur J Cancer 41, 1453-1459 (2005).
Revvity technical publications
- Vikstrom, S., Pulli, P., Hurskainen, P. & Gripenberg-Lerche, C. Multiplexing of DELFIA Cell Proliferation and DNA Fragmentation Assays with Conventional Fluorometric Cell-Based Assays for Identification of Toxic Compounds. Revvity Poster.
- DELFIA Cell Proliferation Kit: Optimized protocol for fixation of suspension cells. Revvity Application Note.
Immunoassay/ELISA conversion
Journal articles
References using capture antibody
- Hu, Z. et al. Detection of hepatitis B virus PreS1 antigen using a time-resolved fluoroimmunoassay. J Immunoassay Immunochem 33, 156–165 (2012).
- May, R. et al. Preclinical development of CAT-354, an IL-13-neutralising antibody, for the treatment of severe uncontrolled asthma. British Journal of Pharmacology (2011).
- Haneda, S. et al. Interleukin-1 Receptor Antagonist Expression in the Equine Endometrium During the Peri-Implantation Period. Domest Anim Endocrin 36, 209-218 (2009).
- Hemmilä, I., Holttinen, S., Pettersson, K. & Lövgren, T. Double-Label Time-Resolved Immunofluorometry of Lutropin and Follitropin in Serum. Clin Chem 33, 2281-2283 (1987).
- Peruski, A.H., Johnson, L.H. & Peruski, L.F. Rapid and Sensitive Detection of Biological Warfare Agents Using Time-Resolved Fluorescence Assays. J Immunol Methods 263, 35-41 (2002).
- Smith, D.R. et al. Comparison of Dissociation-Enhanced Lanthanide Fluorescent Immunoassays to Enzyme-Linked Immunosorbent Assays for Detection of Staphylococcal Enterotoxin B, Yersinia pestis-Specific F1 Antigen, and Venezuelan Equine Encephalitis Virus. Clin Diagn Lab Immun 8, 1070-1075 (2001).
- Zhou, F., Goodsell, A., Uematsu, Y. & Vajdy, M. Prolonged Protection Against Intra-Nasal Challenge with Influenza Virus Following Systemic or Combinations of Mucosal and Systemic Immunizations with a Heat Labile Toxin Mutant. Clin Vaccine Immunol 16, 471-478 (2009).
References using capture antigen
- Lai, R. P. J. et al. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund’s Adjuvants. PLoS ONE 7, e35083 (2012).
- Aggerbeck, H., Gizurarson, S., Wantzin, J. & Heron, I. Intranasal Booster Vaccination Against Diphtheria and Tetanus in Man. Vaccine 15, 307-316 (1997).
- Atti, M.L.C.D. et al. Reactogenicity and Immunogenicity of Adult Versus Paediatric Diphtheria and Tetanus Booster Dose at 6 Years of Age. Vaccine 20, 74-79 (2001).
- Hunolstein, C.V. et al. European Sero-Epidemiology Network: Standardisation of the Results of Diphtheria Antitoxin Assays. Vaccine 18, 3287-3296 (2000).
- Maple, P.A.C. et al. Performance of a Time-Resolved Fluorescence Immunoassay for Measuring Varicella-Zoster Virus Immunoglobulin G Levels in Adults and Comparison with Commercial Enzyme Immunoassays and Merck Glycoprotein Enzyme Immunoassay. Clin Vaccine Immunol 13, 214-218 (2006).
- von Hunolstein, C. et al. Diphtheria Antibody Levels in the Italian Population. Eur J Clin Microbiol 19, 433-437 (2000).
Whole cell-based
- Hardcastle, A. et al. A Duplexed Phenotypic Screen for the Simultaneous Detection of Inhibitors of the Molecular Chaperone Heat Shock Protein 90 and Modulators of Cellular Acetylation. Mol Cancer Ther 6, 1112-1122 (2007).
- McEarchern, J.A. et al. Preclinical Characterization of SGN-70, a Humanized Antibody Directed Against CD70. Clin Cancer Res 14, 7763-7772 (2008).
- Zerwes, H. et al. A Multiparameter Screening Assay to Assess the Cytokine-Induced Expression of Endothelial Cell Adhesion Molecules. Anal Biochem 304, 166-173 (2002).
Revvity technical publications
- DELFIA Immunoassays. Revvity Application Note.
- How to optimize rapid and simple immunoassays. Revvity Application Note.
- Vikstrom, S., Gripenberg-Lerche, C., Hurskainen, P. & Hemmilä, I. A Cell-based DELFIA Assay for Measuring Phosphorylation of Proteins. Revvity Application Note.
Kinase
Journal articles
- Newbatt, Y. et al. Identification of Auhosphorylation Inhibitors of the Inositol-Requiring Enzyme 1 Alpha (IRE1α) by High-Throughput Screening Using a DELFIA Assay. J Biomol Screen (2012).
- Koziolek, E. J. et al. A high-affinity ErbB4Fc fusion protein is a potent antagonist of heregulin-mediated receptor activation. Growth Factors (2012).
- Walton, M. I. et al. CCT244747 is a novel, potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs. Clin. Cancer Res. (2012).
- Liu, Y. et al. Interacting Neuroendocrine and Innate and Acquired Immune Pathways Regulate Neutrophil Mobilization from Bone Marrow following Hemorrhagic Shock. J Immunol 182, 572-580 (2009).
- Toral-Barza, L. et al. Characterization of the Cloned Full-Length and a Truncated Human Target of Rapamycin: Activity, Specificity, and Enzyme Inhibition as Studied by a High Capacity Assay. Biochem Bioph Res Co 332, 304-310 (2005).
- Yamamoto, N. et al. Development of a High-Throughput Fluoroimmunoassay for Syk Kinase and Syk Kinase Inhibitors. Anal Biochem 315, 256-261 (2003).
- Zhang, N. et al. MEK (MAPKK) Inhibitors. Part 2: Structure--Activity Relationships of 4-Anilino-3-Cyano-6,7-Dialkoxyquinolines. Bioorg Med Chem Lett 11, 1407-1410 (2001).
Revvity technical publications
- Tamminem, J. et al. Screening for Specific Antibodies for Ser/Thr Kinase Assays Based on Time-Resolved Fluorescence. Revvity Poster.
- Vikstrom, S., Gripenberg-Lerche, C., Hurskainen, P. & Hemmilä, I. A Cell-based DELFIA Assay for Measuring Phosphorylation of Proteins. Revvity Application Note.
- Vikstrom, S., Korte, M., Pulli, P., Hurskainen, P. & Gripenberg-Lerche, C. A Cell-Based, Microplate Format, DELFIA Assay for Determination of the Activation of MAP Kinase. Revvity Poster.
Multiplexing
Journal articles
- Aggerbeck, H., Nørgaard-Pedersen, B. & Heron, I. Simultaneous Quantitation of Diphtheria and Tetanus Antibodies by Double Antigen, Time-Resolved Fluorescence Immunoassay. J Immunol Methods 190, 171-183 (1996).
- Bookout, J.T. et al. Development of a Dual-Label Time-Resolved Fluorometric Immunoassay for the Simultaneous Detection of Two Recombinant Proteins in Potato. J Agric Food Chem 48, 5868-5873 (2000).
- Hardcastle, A. et al. A Duplexed Phenotypic Screen for the Simultaneous Detection of Inhibitors of the Molecular Chaperone Heat Shock Protein 90 and Modulators of Cellular Acetylation. Mol Cancer Ther 6, 1112-1122 (2007).
- Hemmilä, I., Holttinen, S., Pettersson, K. & Lövgren, T. Double-Label Time-Resolved Immunofluorometry of Lutropin and Follitropin in Serum. Clin Chem 33, 2281-2283 (1987).
- Xu, Y.Y. et al. Simultaneous Quadruple-Label Fluorometric Immunoassay of Thyroid-Stimulating Hormone, 17 Alpha-Hydroxyprogesterone, Immunoreactive Trypsin, and Creatine Kinase MM Isoenzyme in Dried Blood Spots. Clin Chem 38, 2038-2043 (1992).
- Zerwes, H. et al. A Multiparameter Screening Assay to Assess the Cytokine-Induced Expression of Endothelial Cell Adhesion Molecules. Anal Biochem 304, 166-173 (2002).
Revvity technical publications
- Vikstrom, S., Korte, M., Pulli, P., Hurskainen, P. & Gripenberg-Lerche, C. A Cell-Based, Microplate Format, DELFIA Assay for Determination of the Activation of MAP Kinase. Revvity Poster.
- Vikstrom, S., Pulli, P., Hurskainen, P. & Gripenberg-Lerche, C. Multiplexing of DELFIA Cell Proliferation and DNA Fragmentation Assays with Conventional Fluorometric Cell-Based Assays for Identification of Toxic Compounds. Revvity Poster.
Enzymatic assays
Journal articles
- García-Martínez, L.F. et al. In Vitro High-Throughput Screening Assay for Modulators of Transcription. Anal Biochem 301, 103-110 (2002).
- Gottlin, E.B. et al. High-Throughput Screen for Inhibitors of 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase by Surrogate Ligand Competition. J Biomol Screen 8, 332-339 (2003).
- Räbinä, J., Pikkarainen, M., Miyasaka, M. & Renkonen, R. A Time-Resolved Immunofluorometric Assay of Sialyl Lewis x-Degrading Alpha 2,3-Sialidase Activity. Anal Biochem 258, 362-368 (1998).
- Räbinä, J., Mattila, P. & Renkonen, R. Two Time-Resolved Fluorometric High-Throughput Assays for Quantitation of GDP-L-Fucose. Anal Biochem 286, 173-178 (2000).
- Skovbjerg, H. et al. Gliadin is a Good Substrate of Several Transglutaminases: Possible Implication in the Pathogenesis of Coeliac Disease. Scand J Gastroenterol 37, 812-817 (2002).
- Zhang, L., Schwartz, G., O'Donnell, M. & Harrison, R.K. Development of a Novel Helicase Assay Using Electrochemiluminescence. Anal Biochem 293, 31-37 (2001).
Apoptosis
Journal articles
- Walzlein, J. et al. The antitumorigenic response of neural precursors depends on subventricular proliferation and age. Stem Cells 26, 2945-2954 (2008).
Revvity technical publications
- Sippola, K. et al. Cell Based Assay for Studying the Effects of Cytotoxic Agents. Revvity Poster.
- Vikstrom, S., Frang, H., Karvinen, J., Hurskainen, P. & Hemmila, I. A Cell-Based DNA Fragmentation Assay in Microplate Format Using DELFIA Technology. Revvity Poster.
- Vikstrom, S., Pulli, P., Hurskainen, P. & Gripenberg-Lerche, C. Multiplexing of DELFIA Cell Proliferation and DNA Fragmentation Assays with Conventional Fluorometric Cell-Based Assays for Identification of Toxic Compounds. Revvity Poster.
Post-translational modification
Journal articles
- Yuan, Y. et al. A Small-Molecule Probe of the Histone Methyltransferase G9a Induces Cellular Senescence in Pancreatic Adenocarcinoma. ACS chemical biology (2012).
- Xie, W., Ames, R. S. & Li, H. A Cell-Based High-Throughput Screening Assay to Measure Cellular Histone H3 Lys27 Trimethylation with a Modified Dissociation-Enhanced Lanthanide Fluorescent Immunoassay. Journal of Biomolecular Screening (2011).
- Boisclair, M.D. et al. Development of a Ubiquitin Transfer Assay for High Throughput Screening by Fluorescence Resonance Energy Transfer. J Biomol Screen 5, 319-328 (2000).
- Heinke, R. et al. Virtual Screening and Biological Characterization of Novel Histone Arginine Methyltransferase PRMT1 Inhibitors. ChemMedChem 4, 69-77 (2009).
- Kubicek, S. et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol. Cell 25, 473-481 (2007).
- Wynne Aherne, G., Rowlands, M.G., Stimson, L. & Workman, P. Assays for the Identification and Evaluation of Histone Acetyltransferase Inhibitors. Methods 26, 245-253 (2002).
Receptor-ligand binding
Journal articles
Eu-ligand binding (cell membrane-based)
- Robertson, C. R., Pruess, T. H., Grussendorf, E., White, H. S. & Bulaj, G. Generating Orally Active Galanin Analogues with Analgesic Activities. ChemMedChem (2012).
- Gao, X. et al. Europium-Labeled Melanin-Concentrating Hormone Analogues: Ligands for Measuring Binding to Melanin-Concentrating Hormone Receptors 1 and 2. Anal Biochem 328, 187-195 (2004).
- Lee, S. et al. Development of a Time-Resolved Fluorometric Assay for the High Throughput Screening of Melanin Concentrating Hormone Receptor Antagonists. J Pharmacol Toxicol Methods 53, 242-247 (2006).
- Oh, K. et al. Melanin-Concentrating Hormone-1 Receptor Antagonism and Anti-Obesity Effects of Ethanolic Extract from Morus alba Leaves in Diet-Induced Obese Mice. J Ethnopharmacol 122, 216-220 (2009).
- Valenzano, K.J. et al. Development of a Fluorescent Ligand-Binding Assay Using the AcroWell Filter Plate. J Biomol Screen 5, 455-461 (2000).
Eu-ligand binding (whole cell-based)
- Shabanpoor, F. et al. Minimization of relaxin-3 leading to high affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1. Journal of Medicinal Chemistry (2012).
- Greenwalt, D.E., Szabo, J. & Manchel, I. High Throughput Cell-Based Assay of Hemaoietic Progenitor Differentiation. J Biomol Screen 6, 383-392 (2001).
- Handl, H.L., Vagner, J., Yamamura, H.I., Hruby, V.J. & Gillies, R.J. Lanthanide-Based Time-Resolved Fluorescence of in Cyto Ligand-Receptor Interactions. Anal Biochem 330, 242-250 (2004).
- Inglese, J. et al. Chemokine Receptor-Ligand Interactions Measured Using Time-Resolved Fluorescence. Biochemistry 37, 2372-2377 (1998).
- Li, P., Nagarajan, S., Zhu, C. & Selvaraj, P. Recombinant CD16A-Ig Forms a Homodimer and Cross-Blocks the Ligand Binding Functions of Neutrophil and Monocyte Fc(gamma) Receptors. Mol Immunol 38, 527-538 (2002).
Revvity technical publications
- Sippola, K. et al. Europium-labeled Ligands for Receptor Binding Studies. Revvity Poster.
- Syystö, R. et al. Time-Resolved Fluorometric Receptor Ligand Assay for HTS. Revvity Poster.
Europium labeling
Journal articles
- Aggerbeck, H., Nørgaard-Pedersen, B. & Heron, I. Simultaneous Quantitation of Diphtheria and Tetanus Antibodies by Double Antigen, Time-Resolved Fluorescence Immunoassay. J Immunol Methods 190, 171-183 (1996).
- Gao, X. et al. Europium-Labeled Melanin-Concentrating Hormone Analogues: Ligands for Measuring Binding to Melanin-Concentrating Hormone Receptors 1 and 2. Anal Biochem 328, 187-195 (2004).
- Hurskainen, P. et al. Preparation of Europium-Labelled DNA Probes and Their Properties. Nucl Acids Res 19, 1057-1061 (1991).
- Mikola, H., Sundell, A.C. & Hänninen, E. Labeling of Estradiol and Testosterone Alkyloxime Derivatives with a Europium Chelate for Time-Resolved Fluoroimmunoassays. Steroids 58, 330-334 (1993).
- Smith, D.R. et al. Comparison of Dissociation-Enhanced Lanthanide Fluorescent Immunoassays to Enzyme-Linked Immunosorbent Assays for Detection of Staphylococcal Enterotoxin B, Yersinia pestis-Specific F1 Antigen, and Venezuelan Equine Encephalitis Virus. Clin Diagn lab Immun 8, 1070-1075 (2001).
- Stenroos, K., Hurskainen, P., Blomberg, K. & Lindqvist, C. Solid Phase IL-2-IL-2R Alpha Assay with Time Resolved Fluorometry. Immunol Lett 58, 15-18 (1997).
- Xu, Y.Y. et al. Simultaneous Quadruple-Label Fluorometric Immunoassay of Thyroid-Stimulating Hormone, 17 Alpha-Hydroxyprogesterone, Immunoreactive Trypsin, and Creatine Kinase MM Isoenzyme in Dried Blood Spots. Clin Chem 38, 2038-2043 (1992).
- Yamamoto, N. et al. Development of a High-Throughput Fluoroimmunoassay for Syk Kinase and Syk Kinase Inhibitors. Anal Biochem 315, 256-261 (2003).
- Zerwes, H. et al. A Multiparameter Screening Assay to Assess the Cytokine-Induced Expression of Endothelial Cell Adhesion Molecules. Anal Biochem 304, 166-173 (2002).