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Recent Advances in Understanding the Structure and Function Relationship of Multidrug Resistance-Linked ABC Transporter P-glycoprotein

2016· article· en· W2516186110 on OpenAlex
Fei Zhou, Lothar Esser, Di Xia

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

venuePublished in a venue whose home country is Canada.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueJournal of cancer research updates · 2016
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsnot available
Fundersnot available
KeywordsMultiple drug resistanceP-glycoproteinTransporterATP-binding cassette transporterComputational biologyChemistryHigh resolutionFunction (biology)BiologyBiochemistryCell biologyGene

Abstract

fetched live from OpenAlex

Mammalian P-glycoproteins (P-gp) are members of the broad family of ABC transporters and play important physiological roles in establishing physical barriers that limit access of toxic compounds and thus in the pharmacokinetics of these compounds. Cancer cells exploit the presence of P-gp to fend off anti-cancer drugs, rendering them multidrug resistant (MDR). Structural investigations of P-gp involve the expression and isolation of this large integral membrane protein in high quality and in sufficient quantity for it to be amenable to electron microscopic (EM) and crystallographic studies. EM studies have defined the shape of the molecule and delineated its various conformations in solution but major breakthrough in obtaining atomic resolution structures of P-gp were accomplished by X-ray crystallography. Structures with increasing resolution and accuracy in various substrate and inhibitor bound forms are available for analysis and novel mechanistic insights have been obtained. These advances have paved the way for future research to further our understanding of the mechanism of P-gp function and development of potential inhibitors that may reverse MDR in cancer treatment.

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.

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)0.001
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.228
Threshold uncertainty score0.224

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 integrity0.0000.001
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 head0.061
GPT teacher head0.356
Teacher spread0.295 · 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