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Record W6991971447

Investigating the induction of cytosolic hemozoin-containing compartments in «P. falciparum»

2018· dissertation· en· W6991971447 on OpenAlexfundno aff

Bibliographic record

VenueeScholarship@McGill (McGill) · 2018
Typedissertation
Languageen
FieldMedicine
TopicMalaria Research and Control
Canadian institutionsnot available
FundersFonds de recherche du Québec – Nature et technologiesNatural Sciences and Engineering Research Council of CanadaMcGill University
KeywordsPlasmodium falciparumMefloquineCytosolChloroquineIn vitroTransfectionMalariaCell culture
DOInot available

Abstract

fetched live from OpenAlex

Drug resistance and treatment failure in Plasmodium falciparum have plagued the global community for decades and while some progress has been made in elucidating the underpinnings of the resistant phenotype since the discovery of PfCRT, the primary determinant of resistance to chloroquine (CQ), recent findings from our laboratory have added element to the mystery.CQ has been found to induce the formation of hemozoincontaining compartments in the trophozoite-stage parasite's cytosol in a concentrationdependent manner in CQ-sensitive (CQS) parasites but not CQ-resistant (CQR) parasites within the first four hours of drug exposure.Using viral-mediated transfection of CQS and CQR parasites and immunofluorescence assays (IFA), we investigated the origins of these Hz-compartments.Transfected lines did not proliferate, preventing direct confirmation of a possible DV origin.IFAs resulted in nonspecific staining.We established IC 50 values for a range of antimalarials and further investigated the capacity of other quinoline antimalarials mefloquine (MQ) and quinine (QN) to induce this response in CQS or CQR parasites through live cell imaging.MQ and QN did not induce this response, suggesting it may be specific to 4-aminoquinoline drugs.Cloning.......

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 score0.002
Threshold uncertainty score0.006

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)0.0020.001

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 head0.037
GPT teacher head0.304
Teacher spread0.267 · 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
Published2018
Admission routes1
Has abstractyes

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