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Record W2953864295 · doi:10.22215/etd/2019-13608

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and early human pancreatic development

2019· dissertation· en· W2953864295 on OpenAlexaff
Erin M. MacFarlane

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsCarleton University
Fundersnot available
KeywordsAryl hydrocarbon receptorCytochrome P450Endocrine systemPancreasCell cultureEndocrinologyInternal medicineBiologyEmbryonic stem cellEnteroendocrine cellEnzyme inducerIn vitroChemistryCell biologyEnzymeHormoneGeneBiochemistryTranscription factorGeneticsMedicineMetabolism

Abstract

fetched live from OpenAlex

Environmental factors such as pollutants are associated with diabetes incidence. Of particular interest is exposure to persistent organic pollutants (POPs) during critical stages of fetal development. TCDD (2,3,7, is a potent ligand of the aryl hydrocarbon receptor, which leads to induction of cytochrome P450 (CYP) 1A1 enzymes. We hypothesize that POPs such as TCDD accumulate in the pancreas, thereby eliciting stress on developing beta cells through induction of CYP1A1. Here, I exposed rodent alpha and beta cell lines to TCDD in vitro, but did not observe induction of Cyp1a1 gene expression or enzyme activity, meaning that this pathway is not activated in immortalized pancreatic endocrine cell lines. I also differentiated human embryonic stem cells toward pancreatic cell fate in vitro to study how TCDD exposure impacts human beta cell development. I concluded that TCDD might impede normal development of beta cells, potentially through induction of CYP1A1 and other embryonic lineages. I would firstly like to acknowledge my supervisor, Dr. Jenny Bruin, for her support and guidance throughout my project, on-going patience and understanding toward the struggles of stem cell culture, and encouragement through my endless troubleshooting. Thank you to the rest of the Bruin lab members, particularly Kayleigh Rick and Myriam Hoyeck, for occasional scientific support and frequent emotional support. This venture would have been much less enriching without you.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.016
GPT teacher head0.269
Teacher spread0.252 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2019
Admission routes1
Has abstractyes

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