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Record W2917908354

Thermodynamic Characterization of Tetraplex DNA Structures

2018· dissertation· en· W2917908354 on OpenAlexfundno aff
Byul Kim

Bibliographic record

VenueTSpace · 2018
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA and Nucleic Acid Chemistry
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsCharacterization (materials science)DNAComputational biologyComputer scienceChemistryNanotechnologyBiologyMaterials scienceBiochemistry
DOInot available

Abstract

fetched live from OpenAlex

The role of counterion condensation as a dominant force governing the stability of DNA duplexes and triplexes is well established. In contrast, the effect of counterion condensation on the stability of G-quadrupex conformations is poorly understood. Unlike other ordered nucleic acid structures, G-quadruplexes exhibit a specific binding of counterions (typically, Na+ or K+) which are buried inside the central cavity and coordinated to the O6 carbonyls of the guanines forming the G-quartets. While it has been known that the G-quadruplex-to-coil transition temperature, TM, increases with an increase in the concentration of the stabilizing ion, the contributions of the specific (coordination in the central cavity) and nonspecific (condensation) ion binding have not been resolved. In the first part of the work performed in this dissertation, we used G-quadruplexes formed by four different sequences derived from the human telomeric region, c-MYC, and VEGF genes to separate the two ionic contributions. We studied the change in TM of preformed G-quadruplexes following the addition of nonstabilizing ions Li+, Cs+, and TMA+ (tetramethylammonium). Our data suggest that the stabilizing action of cations on the G-quadruplex conformation is, primarily, due to the central ions which act as specifically bound ligands. Nonspecifically bound (condensed) counterions may slightly stabilize the G-quadruplex conformation or exert no influence on its stability (human telomeric G-quadruplexes) or may strongly destabilize it (c-MYC and VEGF). After investigating the salt effect in G-quadruplexes, the latter part of the thesis project was devoted to understanding the folding/unfolding transitions of i-motif, a distinct tetraplex structure formed by c-rich complementary sequences of G-quadruplexes.We described the pH-induced folding/unfolding transitions of i-motifs formed by c-MYC sequence by a linkage thermodynamics-based formalism in terms of three pKa’s of cytosines, namely, an apparent pKa in the unfolded conformation, pKau, and two apparent pKa’s in the folded state, pKaf1 and pKaf2.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.021
Threshold uncertainty score0.749

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.274
Teacher spread0.269 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2018
Admission routes1
Has abstractyes

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