Nicholas Leeper

Publications

• The Genetic Basis of Peripheral Arterial Disease Current Knowledge, Challenges, and Future Directions
  Kullo, I. J., & Leeper, N. J. (2015). The Genetic Basis of Peripheral Arterial Disease Current Knowledge, Challenges, and Future Directions. CIRCULATION RESEARCH, 116(9), 1551-1560.
• Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.
  Shah, N. H., LePendu, P., Bauer-Mehren, A., Ghebremariam, Y. T., Iyer, S. V., & Leeper, N. J. (2015). Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PloS one, 10(6).
• MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype Early Career Committee Contribution
  Maegdefessel, L., Rayner, K. J., & Leeper, N. J. (2015). MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype Early Career Committee Contribution. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 35(1), 2-6.
• Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1 Ali, Z. A., Perez, V. D. J., Yuan, K., Orcholski, M., Pan, S., & Ashley, E. A. (2014). Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1. JOURNAL OF CLINICAL INVESTIGATION, 124(12), 5159-5174.
  
• Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis Kojima, Y., Downing, K., Kundu, R., Miller, C., Dewey, F., & Leeper, N. J. (2014). Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis. JOURNAL OF CLINICAL INVESTIGATION, 124(3), 1083-1097.
  
• Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8 Ahn, G.-O., Seita, J., Hong, B.-J., Kim, Y.-E., Bok, S., & Brown, J. M. (2014). Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(7), 2698-2703.
  
• Alternative Ankle-Brachial Index Method Identifies Additional At-Risk Individuals Nead, K. T., Cooke, J. P., Olin, J. W., & Leeper, N. J. (2013). Alternative Ankle-Brachial Index Method Identifies Additional At-Risk Individuals. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 62(6), 553-559.
  
• Practice-Based Evidence: Profiling the Safety of Cilostazol by Text-Mining of Clinical Notes Leeper, N. J., Bauer-Mehren, A., Iyer, S. V., LePendu, P., Olson, C., & Shah, N. H. (2013). Practice-Based Evidence: Profiling the Safety of Cilostazol by Text-Mining of Clinical Notes. PLOS ONE, 8(5).
  
• Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Leeper, N. J., Raiesdana, A., Kojima, Y., Kundu, R. K., Cheng, H., & Quertermous, T. (2013). Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arteriosclerosis, thrombosis, and vascular biology, 33(1), e1-e10.
  
• Genetics of Peripheral Artery Disease Leeper, N. J., Kullo, I. J., & Cooke, J. P. (2012). Genetics of Peripheral Artery Disease. CIRCULATION, 125(25), 3220-3228.
  
• MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion Maegdefessel, L., Azuma, J., Toh, R., Deng, A., Merk, D. R., & Tsao, P. S. (2012). MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion. SCIENCE TRANSLATIONAL MEDICINE, 4(122).
  
• Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development Maegdefessel, L., Azuma, J., Toh, R., Merk, D. R., Deng, A., & Tsao, P. S. (2012). Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. JOURNAL OF CLINICAL INVESTIGATION, 122(2), 497-506.
  
• MicroRNA-26a Is a Novel Regulator of Vascular Smooth Muscle Cell Function Leeper, N. J., Raiesdana, A., Kojima, Y., Chun, H. J., Azuma, J., & Spin, J. M. (2011). MicroRNA-26a Is a Novel Regulator of Vascular Smooth Muscle Cell Function. JOURNAL OF CELLULAR PHYSIOLOGY, 226(4), 1035-1043.
  
• MicroRNA and Mechanisms of Impaired Angiogenesis in Diabetes Mellitus Leeper, N. J., & Cooke, J. P. (2011). MicroRNA and Mechanisms of Impaired Angiogenesis in Diabetes Mellitus. CIRCULATION, 123(3), 236-238.
  
• Stem Cell Therapy for Vascular Regeneration Adult, Embryonic, and Induced Pluripotent Stem Cells Leeper, N. J., Hunter, A. L., & Cooke, J. P. (2010). Stem Cell Therapy for Vascular Regeneration Adult, Embryonic, and Induced Pluripotent Stem Cells. CIRCULATION, 122(5), 517-526.
  
• Upregulation of the apelin-APJ pathway promotes neointima formation in the carotid ligation model in mouse Kojima, Y., Kundu, R. K., Cox, C. M., Leeper, N. J., Anderson, J. A., & Quertermous, T. (2010). Upregulation of the apelin-APJ pathway promotes neointima formation in the carotid ligation model in mouse. CARDIOVASCULAR RESEARCH, 87(1), 156-165.
  
• Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation Leeper, N. J., Tedesco, M. M., Kojima, Y., Schultz, G. M., Kundu, R. K., & Quertermous, T. (2009). Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 296(5), H1329-H1335.
  
• Clinical problem-solving. Fool's Gold. Leeper, N. J., Dhaliwal, G., Saint, S., & Witteles, R. M. (2008). Clinical problem-solving. Fool's Gold. New England journal of medicine, 359(19), 2035-2041.
  
• Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis Chun, H. J., Ali, Z. A., Kojima, Y., Kundu, R. K., Sheikh, A. Y., & Quertermous, T. (2008). Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. JOURNAL OF CLINICAL INVESTIGATION, 118(10), 3343-3354.
  
• Statin use in patients with extremely low low-density lipoprotein levels is associated with improved survival Leeper, N. J., Ardehali, R., DeGoma, E. M., & Heidenreich, P. A. (2007). Statin use in patients with extremely low low-density lipoprotein levels is associated with improved survival. CIRCULATION, 116(6), 613-618.
  
• Prognostic value of heart rate increase at onset of exercise testing Leeper, N. J., Dewey, F. E., Ashley, E. A., Sandri, M., Tan, S. Y., & Froelicher, V. (2007). Prognostic value of heart rate increase at onset of exercise testing. CIRCULATION, 115(4), 468-474.
  
• One surprise after another Leeper, N. J., Wener, L. S., Dhaliwal, G., Saint, S., & Wachter, R. M. (2005). One surprise after another. NEW ENGLAND JOURNAL OF MEDICINE, 352(14), 1474-1479.
  
• Cloning of a unique lipase from endothelial cells extends the lipase gene family Hirata, K., Dichek, H. L., Cioffi, J. A., Choi, S. Y., Leeper, N. J., & Quertermous, T. (1999). Cloning of a unique lipase from endothelial cells extends the lipase gene family. JOURNAL OF BIOLOGICAL CHEMISTRY, 274(20), 14170-14175.
  
• Proton pump inhibitors and vascular function: A prospective cross-over pilot study Ghebremariam, Y. T., Cooke, J. P., Khan, F., Thakker, R. N., Chang, P., & Leeper, N. J. (2015). Proton pump inhibitors and vascular function: A prospective cross-over pilot study. VASCULAR MEDICINE, 20(4), 309-316.
  
• Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population Shah, N. H., LePendu, P., Bauer-Mehren, A., Ghebremariam, Y. T., Iyer, S. V., & Leeper, N. J. (2015). Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLOS ONE, 10(6).
  
• Improved Reclassification of Mortality Risk by Assessment of Physical Activity in Patients Referred for Exercise Testing Myers, J., Nead, K. T., Chang, P., Abella, J., Kokkinos, P., & Leeper, N. J. (2015). Improved Reclassification of Mortality Risk by Assessment of Physical Activity in Patients Referred for Exercise Testing. AMERICAN JOURNAL OF MEDICINE, 128(4), 396-402.
  
• Effect of Physical Activity Assessment on Prognostication for Peripheral Artery Disease and Mortality Chang, P., Nead, K. T., Olin, J. W., Myers, J., Cooke, J. P., & Leeper, N. J. (2015). Effect of Physical Activity Assessment on Prognostication for Peripheral Artery Disease and Mortality. MAYO CLINIC PROCEEDINGS, 90(3), 339-345.
  
• Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells. Perin, E. C., Murphy, M., Cooke, J. P., Moyé, L., Henry, T. D., & Hirsch, A. T. (2014). Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells. American heart journal, 168(5), 667-673.
  
• Rationale and Design for PACE: Patients with Intermittent Claudication Injected with ALDH Bright Cells Perin, E. C., Murphy, M., Cooke, J. P., Moye, L., Henry, T. D., & Hirsch, A. T. (2014). Rationale and Design for PACE: Patients with Intermittent Claudication Injected with ALDH Bright Cells. AMERICAN HEART JOURNAL, 168(5), 667-673.
  
• Clinical and socioeconomic factors associated with unrecognized peripheral artery disease Chang, P., Nead, K. T., Olin, J. W., Cooke, J. P., & Leeper, N. J. (2014). Clinical and socioeconomic factors associated with unrecognized peripheral artery disease. VASCULAR MEDICINE, 19(4), 289-296.
  
• Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation. Miller, C. L., Haas, U., Diaz, R., Leeper, N. J., Kundu, R. K., & Sczakiel, G. (2014). Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation. PLoS genetics, 10(3).
  
• Coronary Heart Disease-Associated Variation in TCF21 Disrupts a miR-224 Binding Site and miRNA-Mediated Regulation Miller, C. L., Haas, U., Diaz, R., Leeper, N. J., Kundu, R. K., & Sczakiel, G. (2014). Coronary Heart Disease-Associated Variation in TCF21 Disrupts a miR-224 Binding Site and miRNA-Mediated Regulation. PLOS GENETICS, 10(3).
  
• Self-Reported History of Childhood Smoking Is Associated with an Increased Risk for Peripheral Arterial Disease Independent of Lifetime Smoking Burden Priest, J. R., Nead, K. T., Wehner, M. R., Cooke, J. P., & Leeper, N. J. (2014). Self-Reported History of Childhood Smoking Is Associated with an Increased Risk for Peripheral Arterial Disease Independent of Lifetime Smoking Burden. PLOS ONE, 9(2).
  
• The combination of 9p21.3 genotype and biomarker profile improves a peripheral artery disease risk prediction model Downing, K. P., Nead, K. T., Kojima, Y., Assimes, T., Maegdefessel, L., & Leeper, N. J. (2014). The combination of 9p21.3 genotype and biomarker profile improves a peripheral artery disease risk prediction model. VASCULAR MEDICINE, 19(1), 3-8.
  
• Self-reported history of childhood smoking is associated with an increased risk for peripheral arterial disease independent of lifetime smoking burden. Priest, J. R., Nead, K. T., Wehner, M. R., Cooke, J. P., & Leeper, N. J. (2014). Self-reported history of childhood smoking is associated with an increased risk for peripheral arterial disease independent of lifetime smoking burden. PloS one, 9(2).
  
• Association of lower extremity performance with cardiovascular and all-cause mortality in patients with peripheral artery disease: a systematic review and meta-analysis. Morris, D. R., Rodriguez, A. J., Moxon, J. V., Cunningham, M. A., McDermott, M. M., & Golledge, J. (2014). Association of lower extremity performance with cardiovascular and all-cause mortality in patients with peripheral artery disease: a systematic review and meta-analysis. Journal of the American Heart Association, 3(4).
  
• Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus Miller, C. L., Anderson, D. R., Kundu, R. K., Raiesdana, A., Nuernberg, S. T., & Quertermous, T. (2013). Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus. PLOS GENETICS, 9(7).
  
• A hybrid genomic and proteomic biomarker panel accurately predicts peripheral arterial disease status Nead, K. T., Putnam, K., Cooke, J. P., Olin, J. W., & Leeper, N. J. (2013). A hybrid genomic and proteomic biomarker panel accurately predicts peripheral arterial disease status. VASCULAR MEDICINE, 18(3), 165-165.
  
• Walking Impairment Questionnaire Improves Mortality Risk Prediction Models in a High-Risk Cohort Independent of Peripheral Arterial Disease Status Nead, K. T., Zhou, M., Caceres, R. D., Olin, J. W., Cooke, J. P., & Leeper, N. J. (2013). Walking Impairment Questionnaire Improves Mortality Risk Prediction Models in a High-Risk Cohort Independent of Peripheral Arterial Disease Status. CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES, 6(3), 255-261.
  
• Usefulness of the Addition of Beta-2-Microglobulin, Cystatin C and C-Reactive Protein to an Established Risk Factors Model to Improve Mortality Risk Prediction in Patients Undergoing Coronary Angiography Nead, K. T., Zhou, M. J., Caceres, R. D., Sharp, S. J., Wehner, M. R., & Leeper, N. J. (2013). Usefulness of the Addition of Beta-2-Microglobulin, Cystatin C and C-Reactive Protein to an Established Risk Factors Model to Improve Mortality Risk Prediction in Patients Undergoing Coronary Angiography. AMERICAN JOURNAL OF CARDIOLOGY, 111(6), 851-856.
  
• AN ALTERNATIVE ANKLE-BRACHIAL INDEX METHOD IDENTIFIES INDIVIDUALS AT HIGH-RISK FOR CARDIOVASCULAR MORTALITY THAT ARE CURRENTLY OVERLOOKED Nead, K. T., Cooke, J. P., & Leeper, N. J. (2013). AN ALTERNATIVE ANKLE-BRACHIAL INDEX METHOD IDENTIFIES INDIVIDUALS AT HIGH-RISK FOR CARDIOVASCULAR MORTALITY THAT ARE CURRENTLY OVERLOOKED. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 61(10), E2124-E2124.
  
• Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease Leeper, N. J., Myers, J., Zhou, M., Nead, K. T., Syed, A., & Cooke, J. P. (2013). Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease. JOURNAL OF VASCULAR SURGERY, 57(3), 728-733.
  
• Network analysis of unstructured EHR data for clinical research. Bauer-Mehren, A., LePendu, P., Iyer, S. V., Harpaz, R., Leeper, N. J., & Shah, N. H. (2013). Network analysis of unstructured EHR data for clinical research. AMIA Summits on Translational Science proceedings AMIA Summit on Translational Science, 2013, 14-18.
  
• Loss of CDKN2B Promotes p53-Dependent Smooth Muscle Cell Apoptosis and Aneurysm Formation Leeper, N. J., Raiesdana, A., Kojima, Y., Kundu, R. K., Cheng, H., & Quertermous, T. (2013). Loss of CDKN2B Promotes p53-Dependent Smooth Muscle Cell Apoptosis and Aneurysm Formation. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 33(1), E1-?.
  
• Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes. Leeper, N. J., Bauer-Mehren, A., Iyer, S. V., LePendu, P., Olson, C., & Shah, N. H. (2013). Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes. PloS one, 8(5).
  
• Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus. Miller, C. L., Anderson, D. R., Kundu, R. K., Raiesdana, A., Nürnberg, S. T., & Quertermous, T. (2013). Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus. PLoS genetics, 9(7).
  
• Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease Zhou, M., Leeper, N. J., Nead, K. T., Syed, A., Abella, J., & Myers, J. (2012). Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease. VASCULAR MEDICINE, 17(3), 204-205.
  
• The Effect of Angiotensin-Converting Enzyme Inhibitors and Statins on the Progression of Aortic Sclerosis and Mortality Ardehali, R., Leeper, N. J., Wilson, A. M., & Heidenreich, P. A. (2012). The Effect of Angiotensin-Converting Enzyme Inhibitors and Statins on the Progression of Aortic Sclerosis and Mortality. JOURNAL OF HEART VALVE DISEASE, 21(3), 337-343.
  
• Network Analysis Identifies the Orphan Receptor Tyrosine Kinase Ros1 as a Determinant of Glutathione Peroxidase-1 Mediated Vascular Remodeling Ali, Z. A., Perez, V. D. J., Raiesdana, A., Leeper, N. J., Pan, S., & Ashley, E. A. (2011). Network Analysis Identifies the Orphan Receptor Tyrosine Kinase Ros1 as a Determinant of Glutathione Peroxidase-1 Mediated Vascular Remodeling. CIRCULATION, 124(21).
  
• Microrna-21 Regulates Expansion of Abdominal Aortic Aneurysms Through the PTEN/PI3K/AKT Pathway Maegdefessel, L., Azuma, J., Deng, A., Toh, R. M., Merk, D. R., & Tsao, P. S. (2011). Microrna-21 Regulates Expansion of Abdominal Aortic Aneurysms Through the PTEN/PI3K/AKT Pathway. CIRCULATION, 124(21).
  
• Two Decades of Progress in Vascular Medicine Leeper, N. J., Lee, J. T., & Cooke, J. P. (2011). Two Decades of Progress in Vascular Medicine. AMERICAN JOURNAL OF MEDICINE, 124(9), 791-792.
  
• CDKN2B Regulates Cell Fate Decisions in Human Vascular Smooth Muscle Cells Leeper, N. J., Raiesdana, A., Cheng, H., Kundu, R. K., Kojima, Y., & Quertermous, T. (2010). CDKN2B Regulates Cell Fate Decisions in Human Vascular Smooth Muscle Cells. CIRCULATION, 122(21).
  
• The Role of CDKN2B in Vascular Disease Cheng, H. G., Leeper, N. J., Raisedana, A., Kundu, R., Kojima, Y., & Quertermous, T. (2010). The Role of CDKN2B in Vascular Disease. CIRCULATION, 122(21).
  
• Microarray Analysis Identifies miRNA-26a as a Regulator of Vascular Smooth Muscle Cell Phenotypic Modulation Leeper, N. J., Raiesdana, A., Kojima, Y., Chun, H. J., Azuma, J., & Spin, J. M. (2010). Microarray Analysis Identifies miRNA-26a as a Regulator of Vascular Smooth Muscle Cell Phenotypic Modulation. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 30(11), E244-E244.
  
• Endogenous regulation of cardiovascular function by apelin-APJ Charo, D. N., Ho, M., Fajardo, G., Kawana, M., Kundu, R. K., & Quertermous, T. (2009). Endogenous regulation of cardiovascular function by apelin-APJ. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 297(5), H1904-H1913.
  
• Response to letter regarding article, "Statin use in patients with extremely low low-density lipoprotein levels is associated with improved survival" Leeper, N. J., Ardehali, R., DeGoma, E. M., & Heidenreich, P. A. (2008). Response to letter regarding article, "Statin use in patients with extremely low low-density lipoprotein levels is associated with improved survival". CIRCULATION, 117(9), E175-E175.
  
• Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol deGoma, E. M., Leeper, N. J., & Heidenreich, P. A. (2008). Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 51(1), 49-55.
  
• Clinical dilemmas in treating left ventricular thrombus. Leeper, N. J., Gupta, A., Schnittger, I., & Wu, J. C. (2007). Clinical dilemmas in treating left ventricular thrombus. International journal of cardiology, 114(3), e118-9.
  
• Right coronary cameral fistula resulting from surgery of double chamber right ventricle. Leeper, N. J., Gupta, A., Murphy, D. J., & Wu, J. C. (2006). Right coronary cameral fistula resulting from surgery of double chamber right ventricle. Journal of the American Society of Echocardiography , 19(9), 1191 e9-11.
  
• The effect of preoperative statin therapy on cardiovascular outcomes in patients undergoing infrainguinal vascular surgery Ward, R. P., Leeper, N. J., Kirkpatrick, J. N., Lang, R. M., Sorrentino, M. J., & Williams, K. A. (2005). The effect of preoperative statin therapy on cardiovascular outcomes in patients undergoing infrainguinal vascular surgery. INTERNATIONAL JOURNAL OF CARDIOLOGY, 104(3), 264-268.
  
• Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway Desai, T. R., Leeper, N. J., Hynes, K. L., & Gewertz, B. L. (2002). Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway. JOURNAL OF SURGICAL RESEARCH, 104(2), 118-123.
  
• Gender does not influence outcomes after iliac angioplasty Orr, J. D., Leeper, N. J., Funaki, B., Leef, J., Gewertz, B. L., & Desai, T. R. (2002). Gender does not influence outcomes after iliac angioplasty. ANNALS OF VASCULAR SURGERY, 16(1), 55-60.
  
• Regulated expression of a unique lipase in endothelial cells suggests a local role in disease-associated lipid metabolism in the blood vessel wall Hirata, K., Dichek, H. L., Choi, S. Y., Leeper, N. J., Cooper, A. D., & Quertermous, T. (1999). Regulated expression of a unique lipase in endothelial cells suggests a local role in disease-associated lipid metabolism in the blood vessel wall. CIRCULATION, 100(18), 610-610.
  
• Tetracycline-regulatable expression vectors tightly regulate in vitro gene expression of secreted proteins Sturtz, F. G., Cioffi, L., Wittmer, S., Sonk, M. J., Shafer, A., & Platika, D. (1998). Tetracycline-regulatable expression vectors tightly regulate in vitro gene expression of secreted proteins. GENE, 221(2), 279-285.