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Record W7133033960

Assessing a n Novel Synthetic FZD4 Agonist to Rescue Blood Brain Barrier Ddysfunction

2023· dissertation· W7133033960 on OpenAlexaff
Sofia Maureen Zelko

Bibliographic record

VenueTSpace · 2023
Typedissertation
Language
FieldNeuroscience
TopicBarrier Structure and Function Studies
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsBlood–brain barrierAgonistAngiogenesisTight junctionReceptorWnt signaling pathwayHomeostasis
DOInot available

Abstract

fetched live from OpenAlex

The Blood Brain Barrier (BBB) is a selective structure controlling the passage of molecules between the blood and the brain. It is characterized by the formation of tight junctions between endothelial cells (ECs). The Wnt/β-catenin signalling pathway controls angiogenesis and barrier integrity, both crucial for vascular development and homeostasis of the BBB. FZD4 is required for angiogenesis and barrier functions in brain vasculature, forming a receptor complex with WNT7/GPR124/RECK/LRP5/6 to evoke Wnt-mediated signalling in brain vasculature. Our lab has engineered novel synthetic antibody-based Frizzled/LRP Agonists mimicking Wnt ligands. This thesis investigated activation of the FZD4 receptor complexes using F4L6 and its efficiency to promote CNS barrier function and promote recovery in stroke animal models. A GPR124 siRNA knockdown in ECs was established showing F4L6 acts independently of GPR124. Weassessed F4L6 in an endothelin-1 induced ischemic stroke model and showed decreased leakageat day 10 post-stroke and significant behavioural rescue.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.053
GPT teacher head0.362
Teacher spread0.310 · 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
Published2023
Admission routes1
Has abstractyes

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Same venueTSpaceSame topicBarrier Structure and Function StudiesFrench-language works237,207