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- Stack, K. M., et al.
(författare)
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Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
- 2024
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 129:2
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low-angle cross stratified sandstone, thin-bedded granule sandstone, and thick-bedded granule-pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment-deformed sandstone interbedded with broad, unconfined coarser-grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft-sediment deformed laminated, sulfate-bearing mudstone with lenses of low-angle cross-stratified and scoured sandstone; and FA3, comprised of dipping planar, thin-bedded sand-gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand-dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long-lived, habitable lacustrine and deltaic environment within Jezero crater.
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- Phelan, C M, et al.
(författare)
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Classification of BRCA1 missense variants of unknown clinical significance
- 2005
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 42:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- Background: BRCA1 is a tumour suppressor with pleiotropic actions. Germline mutations in BRCA1 are responsible for a large proportion of breast - ovarian cancer families. Several missense variants have been identified throughout the gene but because of lack of information about their impact on the function of BRCA1, predictive testing is not always informative. Classification of missense variants into deleterious/ high risk or neutral/low clinical significance is essential to identify individuals at risk. Objective: To investigate a panel of missense variants. Methods and results: The panel was investigated in a comprehensive framework that included ( 1) a functional assay based on transcription activation; ( 2) segregation analysis and a method of using incomplete pedigree data to calculate the odds of causality; ( 3) a method based on interspecific sequence variation. It was shown that the transcriptional activation assay could be used as a test to characterise mutations in the carboxy-terminus region of BRCA1 encompassing residues 1396 - 1863. Thirteen missense variants (H1402Y, L1407P, H1421Y, S1512I, M1628T, M1628V, T1685I, G1706A, T1720A, A1752P, G1788V, V1809F, and W1837R) were specifically investigated. Conclusions: While individual classification schemes for BRCA1 alleles still present limitations, a combination of several methods provides a more powerful way of identifying variants that are causally linked to a high risk of breast and ovarian cancer. The framework presented here brings these variants nearer to clinical applicability.
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- Johnson, Candice, et al.
(författare)
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Skin sensitization in silico protocol
- 2020
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducing a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.
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