The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Tricyclo-DNA (tcDNA) is a sugar-modified analogue of DNA currently tested for the treatment of Duchenne muscular dystrophy in an antisense approach. Tandem mass spectrometry plays a key role in modern medical diagnostics and has become a widespread technique for the structure elucidation and quantification of antisense oligonucleotides. Herein, mechanistic aspects of the fragmentation of tcDNA are discussed, which lay the basis for reliable sequencing and quantification of the antisense oligonucleotide. Excellent selectivity of tcDNA for complementary RNA is demonstrated in direct competition experiments. Moreover, the kinetic stability and fragmentation pattern of matched and mismatched tcDNA heteroduplexes were investigated and compared with non-modified DNA and RNA duplexes. Although the separation of the constituting strands is the entropy-favored fragmentation pathway of all nucleic acid duplexes, it was found to be only a minor pathway of tcDNA duplexes. The modified hybrid duplexes preferentially undergo neutral base loss and backbone cleavage. This difference is due to the low activation entropy for the strand dissociation of modified duplexes that arises from the conformational constraint of the tc-sugar-moiety. The low activation entropy results in a relatively high free activation enthalpy for the dissociation comparable to the free activation enthalpy of the alternative reaction pathway, the release of a nucleobase. The gas-phase behavior of tcDNA duplexes illustrates the impact of the activation entropy on the fragmentation kinetics and suggests that tandem mass spectrometric experiments are not suited to determine the relative stability of different types of nucleic acid duplexes.

(Table 1) Stable carbon isotope record and calculated recycled DIC for sediment core ANDRA_HTM102

The prominent negative stable carbon isotope excursion in both carbonate and organic carbon recorded in organic-rich sediments deposited during the Toarcian oceanic anoxic event (OAE) has commonly been explained by recycling of 13C-depleted CO2 (the so-called Küspert model). More recently, the massive release of 13C-depleted methane or other forms of 13C-depleted carbon was also proposed to account for the observed negative d13C excursions in organic carbon of terrigenous as well as of marine origin. The occurrence of diagenetic products of the carotenoid isorenieratene (isorenieratane and other aryl isoprenoids) in Toarcian black shales has been regarded as supporting evidence for the Küspert hypothesis as they point to strong stratification of the epicontinental seas. A section of a drill core straddling the Toarcian of the Paris Basin (Cirfontaine-en-Ornois) contained intact isorenieratane, providing evidence that photosynthetic green sulphur bacteria were present at the time of deposition, even prior to the OAE. However, the isorenieratane abundances are very low in the section where the negative d13C excursion in organic carbon and phytane, a chemical fossil derived from chlorophyll, occurs. The abundance of the isorenieratene derivatives increases, once the d13C records have shifted to more positive values. The d13C of isorenieratane (generally circa -13.1 ± 0.5 per mil) indicates that the respired CO2 contribution at the chemocline was low and is thus not likely to be the main cause of the prominent up to 7per mil negative d13C shift recorded in Toarcian organic carbon records.

Implementation guidelines for retiming arterial streets.

Texas Department of Transportation, Austin

Mineral recovery from the noncombustible fraction of municipal solid waste : a proposed project to demonstrate incinerator residue recovery /

This report was written on work performed under Federal solid waste management demonstration grant no. S-801535 awarded to Lowell, Mass. in October, 1972, and cancelled at the request of the grantee in July, 1975.

Directory of Federal statistics for local areas : a guide to sources, urban update 1977-1978 /

Mode of access: Internet.

The memoirs of the Marquise de Keroubec (1785-1859): being extracts from her diaries now presented to English readers for the first time.

Mode of access: Internet.

Artists and people

Mode of access: Internet.

Regestvm Clementis papae v [annus primus-annus nonus]; ex vaticanis archetypis sanctissimi domini nostri Leonis XIII pontificis maximi ivssv et mvnificenta nvnc primvm editvm cvra et stvdio monachorvm ordinis s. Benedicti anno 1884-[1888]

Accompanied by "Tables des Registres de Clément V, pub. par les bénédictins, établies par Yvonne Lanhers sous la direction de Robert Fawtier. Table chronologique, table des incipit." (viii, 68 p. 33 cm (Bibliothèque des écoles françaises d'Athènes et de Rome. 3 sér.)) Published: Paris, E. de Boccard, 1948.

School of Nursing Class of 1981

Top Row: Mary Jo Ambrozy, Carolyn, Ashley, Gail Marie Barbaza, Jeanne Barr, Susan Bauer, Lynn Eva Becker, Christine Bibilikow, Kathy Biehl, Lisa Bloomfield, Bail M. Borowiak, Susan, M. Browning, Diane Louise Burgoon, Camille Carlson, Cindy marie Chaltry, Kathleen Anne Clegg, Ann cline

Row 2: Wendy Cogan, Annette Robin Cole, Barbara Compton, Elizabeth Connors, Norma K. Marshall, Michele Betts, Donna Jean Holihan, Pamela S. Harden, Kathleen McLaughlin, Mary M. Walker, Mary Lohr, Julia Cooney, Carol Crapo, Deborah D. Davis, Mary Dreisig

Row 3: Athena Eary, Eleanor Eckrich, Patti M. Eidenberger, Catherine Elmlinger, Annette Englund, Cynthis Fellencer, Karen Fischer, Carolyn B. Forbes, Nancy Ellen Freedman, Susan P. George, Annette Gervaix, Beverly Glogowski

Row 4: Jayne Goodrich, June A. R. Grimm, Marie Guerrini, Douglas Leon Hankins, Yvonne M. Harwoor, Linda Hecimovich, Catherine M. Herbel, Kelly Hocker, Brenda Lee Horness, Theresa A. Hosey, Karin E. Hunt, Beth Jackson

Row 5: Karen Sue Jaffe, Roland Jemerson, Tamera Johnson, Susan Kaczmarek, Laura S. Keverian, Julie A. Kimbrough, Eva Marie Kline, Nancy L. Kuehn, Margaret J. Labadie, Lori K. Lane, Elizabeth Lang, Linda Lawton, Judy Linden, Peggy Little, Sharon Lois Longe, Claire Lonstein

Row 6: Deloris Macon, Karen Marie Macsay, Susan E. Mapley, Maria Y. Maquera, Ann McCullough, Michael Meade, Barbara Messink, Mary Elizabeth Mick, Susie E. Mikolajewski, Marilyn Millman, Debra A. Mills, Lu Ann Minore, Jean M. Mischel, Terri Ann Mitchell, Catherine Jean Moore, Michelle A. Mourad

Row 7: Mary Lynn Musial, Kathleen Myles, Denise Oliphint, Patrice M. Orlowski, Susan Orne, Carolyn Pernell, Holly Perry, Paula L. Petkoff, Arlene Ann Popovich, Barbara A. Quinn, Carol Reid, Sandra J. Remington, Gisselle Rodriguez, Susan Roelant, Laura S. Rogers, Nancy Rudd

Row 8: Karen Beth Salem, Barbara Santavy, Linda Schairer, Marie B. Schneider, Julie Schoettley, Julie Rose Schuster, Mary V. Seibert, Tracy Shafer, Claire E. Sharda, Susan D. Shortino, Judith Simon, Phillis Simpson, Donna Sledz, Cynthia Smith, Diane L. Smith, Mary Kay Smith

Row 9: Susan R. Smith, Sharon stansberry, Linda Suchocki, Susan Swoiskin, Leslie Ann Urban, Mary B. Van Wingen, Gretchen M. Vermeulen, Verland Z. Walker, Jayne Walworth, Elaine Devorah Webber, Julie Ann Webster, Sora Weller, Julie L. Weyburne, Malorie Whitefield, Frances Wiecha, Anne C. Wise

School of Nursing Class of 1983

Top Row: Barbara A. Fleckenstein, Anne M. Phelan, Julie-Ann Gersin, Laura E. Kemper, Mary Ann McCulloch, Meryl I. Faber, Karen E. Morton, Jennifer S. Miller, Catherine A. Chichester, Dana R. Piper, Harold K. Lohwasser, Michelle A. Lyons, Julia C. Kelly, Deborah L. Rossman, Amy L. Keskey, John F. Nama, Linda Borucki, Michelle M. Bradley, Caroline M. Fischer, Lisa A. Kuhnlein

Row 2: Karen M. Pardo, Laura L. Price, Mollie A. McDonald, Jan M. Grable, Janna S. Nichols, Laura A. Quain, Patricia M. Battel, Claudia J. Koch, Maureen G. D'hondt, Trudy J. Tervo, Linda A. Walz, Cheryl K. Ebling, Patricia A. Merte, Lauri R. Klock, Maria A. Lomibao, Mary E. Eisenhauer, Ellen B. Malvern, Josephine A. Polesnak

Row 3: Yvonne D. Krisel, Rosemary T. Coyne, Janey A. Porterfield, Deborah A. Mulawa, Janet E. Lovelace, Susan P. O'brien, Margaret T. Perrone, Brenda K. Luckhardt, Terry A. Layher, Sharon A. Potonac, Susan K. Watson, Janet A. Servatowski

Row 4: Vivian A. Reeves, Tracey A. Weeks, Marilyn K. Morgan, Terrilynn Phillips, Susan S. Kirk, Robert J. Ziola, Fred Roberts, Karen S. Myron, Pamela M. Przybylski, Mary Jo F. Lafata, Janet A. Scapini, Mary J. Swails

Row 5: Julie E. Reitz, Julie A. Symons, Ave M. Reagor, Catherine A. Regan, Marsha A. Glass, Susan M. Derubeis, Judy L. Goode, Jennifer P. Wylie, Janet L. Nowak, Karen M. Ulfig, Cynthia E. West, Carol A. Czarnecki, Gloria J. Verdi, Lisa D. Singleton

Row 6: Cynthia Wiggins, Monica L. Babyak, Gail M. Ray, Karen S. Desloover, Ladonna L. Christian-Combs, Deborah J. Dunnaback, Deborah A. Cecchini, Nancy A. Neville, Julia H. Grove, Wendy A. Weinfurtner, Susan M. Twigg, Jolynne Vanotteren, Lori A. Clark, Susan T. Savidge

Row 7: Marianne Ojeda, Ann M. Tucker, Lisa A. Valiquette, Sharon J. Bergmann, Elizabeth A. Rice, Marjorie R. Hovis, Laura I. Berry, Janice B. Lindberg, Rhetaugh G. Dumas, Susan B. Steckel, Helen L. Erickson, Kathleen M. Oshea, Tricia A. Richardson, Cheryl L. Sanders, Ann L. Shcoene, Anita M. Bargardi, Constance S. Siler, Anne L. Scott

Row 8: Gassenie Thomas, Victoria L. cadagin, Sheryl A. Strace, Joyce I. Sourbeck, Mary S. Donald, Cindy Tollis, Miriam L. Allis, Julie J. Watson, Patricia A. Shefferly, Nina M. Squire, Carol J. Debrodt, Jennifer A. Dreps, Cynthia B. Stone, Martha A. House, Elizabeth A. Hull, Laurie J. Bommarito, Erin A. Swain, Lisa D. Davis

Row 9: Lisa W. Barak, Charlotte L. Allport, Karen J. Baker, Julie M. Sweet, Pamela R. Armfield, Kathleen A. Hornick, Marcianna M. Davis, Joann L. Holdridge, Barbara A. Black, Scott L. Baker, Lawrene S. Gardipee, Julie A. Hemsteger, Mary Ann Barz, Carla L. Arnett, Danielle L. Bonam, Janice S. Brady, Karen L. Eischer, Amy A. Hing, Marcia L. Hassig, Heidi G. Henn