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.

Ensemble prediction distribution maps of macroalgae for current conditions and four climate change scenarios and high resultion bathymetry for Potter Cove, WAP, Antarctica

Species distribution models (SDM) predict species occurrence based on statistical relationships with environmental conditions. The R-package biomod2 which includes 10 different SDM techniques and 10 different evaluation methods was used in this study. Macroalgae are the main biomass producers in Potter Cove, King George Island (Isla 25 de Mayo), Antarctica, and they are sensitive to climate change factors such as suspended particulate matter (SPM). Macroalgae presence and absence data were used to test SDMs suitability and, simultaneously, to assess the environmental response of macroalgae as well as to model four scenarios of distribution shifts by varying SPM conditions due to climate change. According to the averaged evaluation scores of Relative Operating Characteristics (ROC) and True scale statistics (TSS) by models, those methods based on a multitude of decision trees such as Random Forest and Classification Tree Analysis, reached the highest predictive power followed by generalized boosted models (GBM) and maximum-entropy approaches (Maxent). The final ensemble model used 135 of 200 calculated models (TSS > 0.7) and identified hard substrate and SPM as the most influencing parameters followed by distance to glacier, total organic carbon (TOC), bathymetry and slope. The climate change scenarios show an invasive reaction of the macroalgae in case of less SPM and a retreat of the macroalgae in case of higher assumed SPM values.

Integrated motorist information (IMIS) feasibility and design study. Phase II: generalized methodology for IMIS feasibility studies. Volume 2--validation and application of feasibility study handbook. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Generalized methodology for conducting industrial toxicity reduction evaluations (TREs) /

Mode of access: Internet.

Phase I: developing generalized driving while intoxicated (DWI) school curricula. Interim report.

National Highway Traffic Safety Administration, Washington, D.C.

Deficient generalized Fibonacci maximum path graphs /

"UILU-ENG 78 1739."

Generalized Ramsey numbers for stars /

"UIUCDCS-R-81-1050"--Cover.

A generalized assembler.

Issued also as thesis (M.S.) University of Illinois.

Characteristic impedances of generalized strip-transmission lines.

Mode of access: Internet.

A generalized lexical scanner for a translator writing system.

Originally presented as the author's thesis (M.S.), University of Illinois at Urbana-Champaign.

Program manual, NOR network transduction by generalized gate merging and substitution : (reference manual of NOR network transduction programs NETTRA-G3 and NETTRA-G4) /

Includes bibliographical references.