2009  - 2010

Fellows in Clinical Chemistry

Laura Bechtel

Laura Bechtel, Ph.D. (2007-2010)  PIC# 2566    

Birthplace: Windsor, Ontario, Canada.

College: Colorado State University, Ft. Collins, CO.

Graduate School: University of Utah.

Interests in Pathology: Clinical Toxicology, Clinical Chemistry, Molecular Diagnostics, Mass Spectrometry, Cardiovascular Disease, Tumor Markers.

Peer Reviewed Publications -

  • Lawrence DT, Bechtel LK, Charlton NP, Boyle JS, Kirk MA, Holstege CP. Falsely elevated lactate measurement after ethylene glycol ingestion. NACCT, Toronto, Canada.  September, 2008. Clinical Toxicology (publication pending).
  • Bechtel LK, Lawrence DT, Holstege CP. Cross-reactivity of Veratrum viride Steroid Alkaloid Compounds with a Digoxin Clinical Chemistry Assay. NACCT, Toronto, Canada.  September, 2008. Clinical Toxicology (publication pending). 
  • Bechtel LK, Charlton NP, Holstege CP. Glucose Uptake Sensitivity in Adipose and Cardiac Cells in Response to Three Classes of Calcium Channel Blockers. NACCT, Toronto, Canada.  September, 2008. Clinical Toxicology (publication pending). 
  • Bechtel L., Haverstick D., Holstege C. Verapamil toxicity dysregulates the phosphatidylinositol 3-kinase pathway. Acad Emerg Med. 2008 Apr;15(4):368. 
  • Klimowski, L. (Bechtel, L.), Garcia, B., Schroeder, M., Shabanowitz, J., Hunt, D., and Virshup, D. Site-specific casein kinase I epsilon-dependent phosphorylation of Dishevelled modulates beta-catenin signaling. FEBS J. 2006 Oct;273(20):4594-602.
  • Klimowski, L. (Bechtel, L.), Garcia, B., Hunt, D. and Virshup, D. Casein kinase I epsilon phosphorylation of Dishevelled at Ser 139/142 attenuates Wnt signal transduction. Dissertation (2005).
  • Swiatek, W., Tsai, I., Klimowski, L. (Bechtel, L.), Pepler, A., Barnette, J., Yost, Virshup, D. Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. (2004)  279: 13011-13017.
  • Clark HF, Gurney AL, Abaya E.,... Klimowski L. (Bechtel, L.), et. al., (52 authors). The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70.  Epub 2003 Sep 15.
  • Simmons, L., Reilly, D., Klimowski, L. (Bechtel, L.), T. Shantha Raju, Meng, G., Sims, P., Hong, Ky., Shields, R., Damico, L., Rancatore, P., Yansura, D. Expression of full-length immunoglobulins in Escherichia coli:  rapid and efficient production of aglycosylated antibodies. J. Imm. Methods (2002) 263:133-147.
  • Klimowski, L. (Bechtel, L.), Ramaswamy, D., Tripp, C.  Molecular cloning, expression and enzymatic activity of a thioredoxin peroxidase from Dirofliaria immitis. Mol. Biochem. Parasitology (1997) 90:297-306.
  • Klimowski, L. (Bechtel, L.), Rayms-Keller, A., Olson, K., Yang, R., Tessari, J., Carlson, J. and Beaty, B.  Inducibility of a molecular bioreporter system by heavy metals. Environmental Toxicology and Chemistry (1996) 15:85-91.
  • Higgs, S., Olson, K., Klimowski, L. (Bechtel, L.), Powers, A., Carlson, J., Possee, R. and Beaty, B.  Mosquito sensitivity to scorpion neurotoxin expressed in an infectious Sindbis virus vector.  Insect Mol. Bio. (1995) 4:97-103.

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Podium Presentations -

  • Bechtel, L.K. and Holstege.  Verapamil toxicity induces dysregulation of the insulin-dependent phosphatidylinositol 3-kinase pathway.  Southeastern SAEM Annual Meeting.  March 23-24, 2007. Wilmington, NC.

Abstract Presentations -

  • Lawrence DT, Bechtel LK, Charlton NP, Boyle JS, Kirk MA, Holstege CP. Falsely elevated lactate measurement after ethylene glycol ingestion. NACCT, Toronto, Canada.  September, 2008. Clinical Toxicology (publication pending).
  • Bechtel LK, Lawrence DT, Holstege CP. Cross-reactivity of Veratrum viride Steroid Alkaloid Compounds with a Digoxin Clinical Chemistry Assay. NACCT, Toronto, Canada.  September, 2008. Clinical Toxicology (publication pending).
  • Bechtel LK, Lawrence DT, Holstege CP. Cross-reactivity of Veratrum viride Steroid Alkaloid Compounds with a Digoxin Clinical Chemistry Assay. NACCT, Toronto, Canada.  September, 2008. Clinical Toxicology (publication pending).
  • Bechtel, L.K. and Poulter, M. "Evaluation of Previously Extracted Viral RNA with the GeneXpert® Enterovirus Assay for Use with Samples of Limited Quantity". Clinical Virology Symposium/ Pan American Society for Clinical Virology. April 27-29, 2008. Daytona Beach, FL.
  • Bechtel, L.K. and Holstege. Verapamil toxicity induces dysregulation of the insulin-dependent phosphatidylinositol 3-kinase pathway. SAEM Annual Meeting. May 16-19, 2007.  Chicago, IL. Southeastern SAEM Annual Meeting. March 23-24, 2007. Wilmington, NC. Acad Emerg Med 2007;14(5): S51.
  • Bechtel, L.K. Haverstick, D.M. and Holstege. High dose insulin reverses calcium channel blocker inhibition of glucose uptake in an adipocyte model. SAEM Annual Meeting. May 16-19, 2007. Chicago, IL. Acad Emerg Med 2007;14(5): S195.
  • Klimowski, L. (Bechtel, L.K.), Garcia, B., Hunt, D., and Virshup, D.  Identification of in vivo phosphorylation sites of CKIe substrates in the Wnt signaling pathway. Wnt Signal Transduction Meeting. May 20-23, 2004.  Ann Arbor, MI.
  • Klimowski, L. (Bechtel, L.K.), Schwall, R., Taylor, S. and Blumenthal, D. Protein kinase A and A-kinase anchoring proteins are differentially regulated in normal vs. oncogenic mammalian breast cancer cell lines. Summer Intern Research Symposia. August 15, 2001; S. San Francisco, CA.
  • Klimowski, L. (Bechtel, L.K.), Reilly, D. and Yansura, D. Full-length antibody expression in Escherichia coli. Genentech-Asliomar, CA 1998.
  • Tripp,C., Klimowski, L. (Bechtel, L.K.), Blehm, S. and Grieve, R.  A Dirofilaria immitis cDNA clone encodes a homolog of the astacin family of zinc endopeptidases. Annual Parasitology Meeting. August 20-25, 1998.
  • Tripp, C., Klimowski, L. (Bechtel, L.K.), Ramaswamy, C. and Grieve, R.  A Dirofilaria immitis larval cDNA clone encoding a homology of mammalian MIF.  Keystone Symposia, Molecular Helminthology: an integrated approach.  February 22-28, 1996; Santa Fe NM.
  • Tripp, C., Klimowski, L. (Bechtel, L.K.), Mika-Grieve, M., Frank, R. and Grieve, R.  Identification and molecular cloning of Dirofilaria immitis genes using immune dog sera. 62nd AMCA Annual Meeting.  March 24-28, 1996.  Norfolk, Virginia.

Reviews -

  • Lawrence D, Bechtel LK, Walsh JP, Holstege CP. The Evaluation and Management of Acute Poisoning Emergencies. Minerva Med. 2007 Oct;98(5):543-68.

Non-peer reviewed invited articles -          
Periodicals -

  • Holstege CP, Dobmeier SG, Bechtel LK. Critical Care Toxicology. Emerg Med Clin NA. August 2008 publication pending.
  • Bechtel L, Holstege CP: Criminal Poisoning: Drug Facilitated Sexual Assault. Emerg Med Clin NA 2007;25:499-525.
  • Holstege CP, Bechtel L, Reilly T, Dobmeier S: Unusual but Potential Agents of Terrorists. Emerg Med Clin NA 2007;25:549-566.
  • Lawrence DT, Dobmeier SG, Bechtel LK, Holstege CP: Food Poisoning. Emerg Med Clin NA 2007;25:357-373.

Textbook -

  • Holstege CP, Reilly TH, Bechtel LK. Other Agents. In McFee RB & Leikin JB (eds): Toxico-terrorism. McGraw-Hill Co., Inc. 2008: 319-326.

Patents -

  • Simmons, L., Reilly, D Klimowski, L. (Bechtel, L.K.), Yansura, D.  Separate-cistron contructs for secretion of aglycosylated antibodies from prokaryotes.  Issued United States Patent #6,979,556, 2005.
  • Klimowski, L. (Bechtel, L.K.), and Tripp C Antiparasitic helminth larval thiol specific antioxidant-antibodies, and uses thereof. Issued United States Patent # 6,489,448, 2002.
  • Klimowski, L. (Bechtel, L.K.), and Tripp C.  Parasitic helminth larval thiol specific antioxidant proteins and nucleic acid molecules. Issued United States Patent # 5,744,593, 1998; 6,031,077, 2000April 28, 1998.

Grants and Awards -

  • Verapamil toxicity induces dysregulation of the insulin-dependent phosphatidylinositol 3-kinase pathway.  Best Basic Science Presentation 2007.  SAEM Annual Meeting.  Presented May 31, 2007. Wilmington, NC.
  • Cross reactivity of Veratrum viride with digoxin assays. American Academy of Clinical Toxicology Travel Award, 2008. $750.
  • Glucose uptake sensitivity in cardiac vs. skeletal muscle cells in CCB toxicity. Study sponsor: American Academy of Clinical Toxicology-Lampe-Kunkle Travel Award. 2008. $750.
  • Evaluation of Previously Extracted Viral RNA with the GeneXpert® Enterovirus Assay for use with Samples of Limited Quantity. Travel Award, 2008 Clinical Virology Symposium/ Pan American Society for Clinical Virology. $750.
  • Cross-Reactivity of False Hellebore Steroid Compounds with a Digoxin Clinical Chemistry Assay. AACT Lampe-Kunkle Memorial Award. 2007. $2,250.
  • Glucose Uptake Sensitivity in Cardiac vs Skeletal Muscle Cells in Calcium Channel Blocker Toxicity. American Academy of Clinical Toxicology Research Grant. 2007. $3,500 .
  • Casein kinase I (CKI) phospho-regulation of canonical Wnt signal transduction in Colon Cancer. University of Utah Graduate Research Grant Award. 2003-2004. $10,000.
  • Development of real time PCR assays to quantify levels of protein kinase A (PKA) regulatory subunits in Her2 mouse xenographs and clinical biopsies. Genentech, Inc. Summer Internship Award. 2001. $12,000.

Manuscript Reviewer -

  •   Academic Emergency Medicine 

Abstract Reviewer -

  • North American College of Clinical Toxicology, 2007 & 2008
  • XXVI International Congress of the European Association of Poisons Centers and Clinical Toxicologists - 2007

Current Research -

  • Cross reactivity of Veratrum viride with digoxin assays. Study sponsor: AACT Lampe-Kunkle Memorial Award. Study Coordinating Center: University of Virginia. Principal Investigators for University of Virginia: Laura Bechtel. Initiated September, 2007.
  • Glucose uptake sensitivity in cardiac vs. skeletal muscle cells in CCB toxicity. Study sponsor: AACT Lampe-Kunkle Memorial Award. Study Coordinating Center: University of Virginia. Principal Investigators for University of Virginia: Laura Bechtel. Initiated September, 2007.
  • Neoprofen plasma levels in extremely low birth weight infants and their relationship to end-organ blood flow. Principle investigators for University of Virginia: Josh Attridge. Initiated July 2007.

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Brian N. Kelly, Ph.D. (2009-2012)  PIC#

Birthplace: Bethesda, MD

College: University of Colorado, Boulder, CO

Graduate School: University of Utah, Salt Lake City, UT

Interest in Pathology:

LindsayLegendreLindsay Legendre, Ph.D (2008-2011)  PIC# 2359

Birthplace: Winston-Salem, NC

College: Richard Stockton College of NJ

Graduate School: Bioanalytical Chemistry, University of Virginia, Charlottesville, VA

Post Doctoral: Chemistry, University of Virginia, Charlottesville, VA

Interest in Pathology: Clinical chemistry and molecular diagnostics

Peer Reviewed Publications -

*Authors contributed equally to the work as documented on the publication.

  • Lindsay A. Legendre, Carleen J. Morris, Rebecca McClure, Annelise Barron and James P. Landers.  "Towards a Simplified Microfluidic Device for Ultrafast Genetic Analysis With Sample In/Answer-Out Capability: Application to T-Cell Lymphoma Diagnosis", Submitted to Journal of Laboratory Automation, 2008.
  • Joan M. Bienvenue*, Lindsay A. Legendre*, Jerome P. Ferrance and James P. Landers.  "An Integrated Microfluidic Device for DNA Purification and PCR Amplification of STRs: Interfacing Microfluidics and Conventional Instrumentation", Submitted to Journal of Forensic Science 2007.
  • Jian Wen, Lindsay A. Legendre, Joan M. Bienvenue, James P. Landers.  "Nucleic Acid Purification in Microfludic Devices", Submitted to Analytical Chemistry 2007.
  • Joseph A. C. Humphrey, Jorge L. Rosales, Lindsay A. Legendre, J. Patrick LeDuc and James P. Landers.  "Vortex Dynamics in Confined Counter-Current Shearing Flows with Applications to Mixing", International Journal of Heat and Fluid Flow. (In press)
  • Michael G. Roper, Christopher J. Easley, Lindsay A. Legendre, James P. Landers. "Completely Non-Contact Temperature Control and Sensing on a Microfluidic Chip" Analytical Chemistry 2007, 79(4), 1294-1300.
  • Christopher J. Easley*, James M. Karlinsey*, Joan M. Bienvenue*, Lindsay A. Legendre*, Michael G. Roper, Molly Hughes, Tod Merkel, Eric Hewlett, Jerome P. Ferrance, and James P. Landers.  "A Fully-Integrated Microfluidic Genetic Analysis System with Sample in-Answer out Capability".  Proceedings of the National Academy of Sciences 2006, 109(51), 19272-19277.
  • Lindsay A. Legendre*, Joan M. Bienvenue*, Michael G. Roper, Jerome P. Ferrance, James P. Landers.  "A Valveless Microfluidic Sample Preparation Device for DNA Extraction and Amplification Using Conventional Instrumentation".  Analytical Chemistry 2006, 78, 1444-1451.
  • Christopher J. Easley*, Lindsay A. Legendre*, Michael G. Roper, Thomas A. Wavering, Jerome P. Ferrance, James P. Landers.  "Extrinsic Fabry-Perot Interferometry for Noncontact Temperature Control of Nanoliter-Volume Enzymatic Reactions in Glass Microchips".  Analytical Chemistry, 2005, 77, 1038-1045.

Non-Peer Reviewed Publications -

  • Lindsay A. Legendre, Jerome P. Ferrance and James P. Landers.  Microfluidic Devices for Electrophoretic Separations: Fabrication and Use.  In The Handbook of Capillary and Microchip Electrophoresis and Associated Microtechniques (3rd Edition), James P. Landers, Eds; CRC Press: Boca Raton, 2007; pp 335-358.
  • Christopher J. Easley, Lindsay A. Legendre, James P. Landers, and Jerome P. Ferrance.  Rapid DNA Amplification in Glass Microdevices. In Methods in Molecular Biology, 339, Charles S. Henry, Eds; Humana Press: New Jersey, 2006; pp 217-231.

Awards -         

  • 2008 - Paul E. Strandjord Young Investigator Award winner, Academy of Clinical Laboratory Physicians and Scientists
  • 2008 - Award for the best clinical science presentation, 4th Annual Pathology Research Retreat, University of Virginia
  • 2005 - ACS Women Chemists Committee Travel Award Sponsored by Eli Lilly & Company
  • 2004 - 2nd place at the 4th Annual Robert J. Huskey Graduate Research Exhibition
  • 1997 - 2001 - College Scholars Scholarship - funded by The Richard Stockton Collegeof NJ Foundation

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Leann MikeshLeann Mikesh, Ph.D. (2006-2009)  PIC# 2522 

Birthplace: Battle Creek, MI.

College: Michigan State University.

Graduate School: MS in Clinical Laboratory Science; PhD in Pathology, Michigan State University.

Post Doctoral: Biological Mass Spectrometry (Donald Hunt), University of Virginia.

Interests in Pathology: Clinical Chemistry, Molecular Diagnostics, Immunology and Antigen Presentation, Mass Spectrometry, Transplantation, Tumor Immunology and Immunotherapy.

Peer Reviewed Publications -

  • Mikesh LM, Bruns DE. Stabilization of glucose in blood specimens: mechanism of delay in fluoride inhibition of glycolysis. Clin Chem. 2008 May;54(5):930-2.
  • Mikesh LM, Crowe SE, Bullock GC, Taylor NE, Bruns DE. Celiac disease refractory to a gluten-free diet? Clin Chem. 2008 Feb;54(2):441-4.
  • Zarling AL, Polefrone JM, Evans AM, Mikesh LM, Shabanowitz J, Lewis ST, Engelhard VH, Hunt DF.  Identification of Class I MHC Associated Phosphopeptides as Targets for Cancer Immunotherapy.  PNAS 103, 14889-94, 2006.
  • Mikesh LM, Ueberheide BM, Chi A, Syka JEP, Coon JJ, Shabanowitz J, Hunt DF.  The Utility of ETD Mass Spectrometry in Proteomic Analysis.  Biochimica et Biophysica Acta-Proteins and Proteomics 1764, 1811-22, 2006.
  • Hopkins (Mikesh) LM, Davis JM, Buchli R, VanGundy RS, Schwartz KA, Gerlach JA:  MHC Class I Associated Peptides Identified from Normal Platelets and from Individuals with Idiopathic Thrombocytopenic Purpura.  Human Immunology 66, 874-883, 2005. 
  • Hopkins (Mikesh) LM, Schall M, Leykam JF, Gerlach JA:  Characterization of Major Histocompatibility Complex Associated Peptides from a Small Volume of Whole Blood.  Analytical Biochemistry 328, 155-161, 2004. 
  • Hopkins (Mikesh) LM, Bull PJ, Gerlach JA, Bull RW:  Further Characterization of HLA Typing Homozygous Typing Cell Lines at the LMP2 Polymorphic Codon 60 by an ARMS Typing Method.  Human Immunology 53, 183-187, 1997.

Podium Presentations -  

  • Mikesh LM, Polefrone JM, Zarling AL, Evans AM, Shabanowitz J, Hunt DF, Engelhard VH:  Differential Expression of HLA-A2 and HLA-B7 phosphorylated peptides on cancer and non-cancer cells: New candidates for immunotherapy.  University of Virginia 3rd Annual Pathology Research Retreat, February 2007.
  • Hopkins LM, Polefrone JM, Zarling AL, Evans AM, Shabanowitz J, Hunt DF, Engelhard VH:  Differential expression of HLA-A2 and HLA-B7 phosphorylated peptides on cancer and non-cancer cells:  New candidates for immunotherapy.  American Society for Histocompatibility and Immunogenetics 31st Annual Meeting, October 2005, Washington DC. 
  • Hopkins (Mikesh) LM, Polefrone JM, Zarling AL, Evans AM, Shabanowitz J, Hunt DF, Engelhard VH:  Differential display of MHC class I HLA-A2 phosphorylated peptides on melanoma:  Potential candidates for immunotherapy.  The 19th International Pigment Cell Conference, September 2005, Reston, VA. 
  • Hopkins (Mikesh) LM, Polefrone JM, Zarling AL, Evans AM, Shabanowitz  J, Hunt DF, Engelhard VH:  Differential Expression of HLA-A2 and HLA-B7 phosphorylated peptides on cancer and non-cancer cells: New candidates for immunotherapy.  University of Virginia Chemistry Department Post-doctoral Summer Seminar Series. June 2005.
  • Hopkins (Mikesh) LM, Davis JM, Schwartz KA, Gerlach JA:  Glycoprotein Ib peptide presented by MHC class I on platelets from individuals with ITP.  American Society for Histocompatibility and Immunogenetics 28th Annual Meeting, October 2002, Nashville, TN. 

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Abstract Presentations -   

  • Syka JEP, Coon JJ, Ueberheide BM, Chi A, Geer LY, Hopkins (Mikesh) LM, Bai DL, Shabanowitz J, Hunt DF:  Electron Transfer Dissociation (ETD): Extending the Reach of Mass Spectrometry in Peptide and Protein Analysis. The 7th International Symposium on Mass Spectrometry in the Health and Life Sciences.  August 2005, San Francisco, CA.
  • Polefrone JM, Hopkins (Mikesh) LM*, Zarling AL, Shabanowitz J, Engelhard VH, Hunt DF (*author order changed after abstract submission):  Differential expression of class I, HLA-A2 phosphopeptides on tumor cells:  Characterization of potential candidates for immunotherapy or a cancer vaccine.  Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics.  June 2005, San Antonio, TX.
  • Hopkins (Mikesh) LM, Polefrone JM, Zarling AL, Geer LY, Bai DL, Chi A, Coon JJ, Syka JEP, Engelhard VH, Shabanowitz J, Hunt DF:  Sequence analysis of HLA-B7 peptides by ETD mass spectrometry:  Comparative analysis of phosphopeptides on cancer and non-cancer cells.  Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics. June 2005, San Antonio, TX.
  • Syka JEP, Coon JJ, Ueberheide BM, Chi A, Hopkins (Mikesh) LM, Bai DL, Shabanowitz J, Hunt DF:  Electron transfer dissociation: The end of the FT-ICR monopoly on c and z-type ions.  The 53rd Annual Conference on Mass Spectrometry. May 2005, Saitama, Japan.
  • Syka JEP, Coon JJ, Ueberheide BM, Chi A, Hopkins (Mikesh) LM, Bai DL, Shabanowitz J, Hunt DF:  Electron Transfer Dissociation (ETD): Instrumentation, Chemistry, and Applications. The 5th North American FT-ICR MS Conference, April 2005 Key West, FL.
  • Hopkins (Mikesh) LM, Davis JM, Schwartz KA, Gerlach JA:  Autoimmunity in ITP:  Role of HLA-B7 and GPIb peptide.  The American Society of Hematology 44th Annual Meeting and Exposition, December 2002, Philadelphia, PA.  
  • Hopkins (Mikesh) LM, Schall M, Leykam JF, Gerlach JA: An in vivo representation of platelet and white blood cell major histocompatibility complex (MHC) associated peptides using mild acid wash of whole cells and LC-MS/MS.  Proceedings of the 50th ASMS Conference on Mass Spectrometry and Allied Topics, June 2002, Orlando FL.
  • Hopkins (Mikesh) LM, Gerlach JA, Frazer T, Veray G:  Analysis of TAP1, TAP2, and LMP2 polymorphisms with IDDM in a Puerto Rican population.  American Diabetes Association 57th Annual Scientific Sessions, June 1997, Boston MA. 

Book Chapters -

Hopkins (Mikesh) LM, Shabanowitz J, Hunt DF:  Immunology: Identification of Peptides Bound to MHC.  In: Encyclopedia of Mass Spectrometry, Volume 2:  Peptides and Proteins.  Elsevier Science, Oxford, 2004.  

Awards -

  • 1994-95 - Michigan State University College of Natural Science Graduate Student Office Fellowship
  • 2002 - Michigan State University College of Veterinary Medicine Graduate School Fellowship
  • 2002 - Michigan State University Graduate School Dissertation Completion Fellowship
  • 2002 - American Society of Histocompatibility and Immunogenetics Scholar Award
  • 2007 - American Association for Clinical Chemistry Past Presidents' Fellowship

Patents -

Engelhard VH, Zarling AL, Hunt DF, Evans AM, Shabanowitz J, Polefrone JM, Hopkins (Mikesh) LM.  Phosphopeptide antigens associated with MHC molecules.  US Patent Pending.

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