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Record W1495070809

An analysis of human cytomegalovirus gene usage A

2012· dissertation· en· W1495070809 on OpenAlexfundno aff
Sepher Seirafian

Bibliographic record

VenueORCA Online Research @Cardiff (Cardiff University) · 2012
Typedissertation
Languageen
FieldMedicine
TopicCytomegalovirus and herpesvirus research
Canadian institutionsnot available
FundersInstitute of Infection and ImmunityMedical Research CouncilDirectorate for Biological SciencesBiotechnology and Biological Sciences Research CouncilUniversity of GlasgowBritish Heart FoundationWellcome Trust
KeywordsHuman cytomegalovirusGeneBiologyMerlin (protein)EpitopeMolecular biologyContext (archaeology)Western blotMutantVirologyGeneticsAntibody
DOInot available

Abstract

fetched live from OpenAlex

HCMV encodes a plethora of immune-modulating functions, many of which have yet to
\nbe assigned to specific genes. In prospect of performing high-throughput screens to
\nidentify and characterise such functions, a library of recombinant adenoviruses (RAds)
\neach encoding a V5 epitope-tagged HCMV protein was generated. Protein expression
\nwas validated and characterised for the vast majority of RAds by western blot and
\nimmunofluorescence.
\nHCMV has been reported to both upregulate cell surface expression of Fas, and render
\ncells resistant to Fas-mediated killing. This thesis demonstrated that Fas levels are
\nmarkedly reduced at the surface of HCMV-infected cells as an early function that
\npersists through the late phase. Screening a panel of HCMV deletion mutants
\neliminated 83 genes as not required for Fas downregulation, while screening the RAd
\nlibrary did not identify any single HCMV gene as being sufficient for this function.
\nDeep sequencing of the HCMV transcriptome recently led to the identification of
\nUL150A as a novel protein-coding gene. To test this prediction, UL150A was tagged
\nwithin the strain Merlin genome. UL150A was shown to encode multiple protein
\nproducts, and be expressed with early and late kinetics.
\nIn a screen of the RAd library, gpUL4 was observed to be secreted from cells. To
\ninvestigate this function in the context of HCMV infection, an epitope-tag was inserted
\nat the 3’-end of the UL4 gene in the strain Merlin genome. Tagged gpUL4 was secreted
\nfrom cells infected with strain Merlin. Secreted gpUL4 was more heavily glycosylated,
\nand produced in greater abundance than its intracellular counterpart late in infection.
\nActive secretion would be consistent with gpUL4 acting as a virokine, cytokine or
\ncytokine/chemokine-binding protein. gpUL4 purified from supernatants of Merlin- or
\nRAd-UL4-infected cells inhibited NK cell degranulation. Furthermore, gpUL4 did not copurify
\nwith virus particles, indicating it is unlikely to be a virion component.

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)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Bibliometrics, Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesResearch integrity
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.747
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0130.010
Science and technology studies0.0010.001
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0010.003
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 head0.074
GPT teacher head0.404
Teacher spread0.330 · 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; both teacher heads agree on what is shown here.

Study designObservational
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

Citations2
Published2012
Admission routes1
Has abstractyes

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