| 121. |
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| 122. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 123. |
- Allen, S. L., et al.
(författare)
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C-13 transport studies in L-mode divertor plasmas on DIII-D
- 2005
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 337-39:03-jan, s. 30-34
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Tidskriftsartikel (refereegranskat)abstract
- (CH4)-C-13 was injected with a toroidally-symmetric gas system into 22 identical lower-single-null L-mode discharges on DIII-D. The injection level was adjusted so that it did not significantly perturb the core or divertor plasmas, with a duration of similar to 3 s on each shot, for a total of similar to 300 T L of injected particles. The plasma shape remained very constant; the divertor strike points were controlled to similar to 1 cm at the divertor plate. At the beginning of the subsequent machine vent, 29 carbon tiles were removed for nuclear reaction analysis of C-13 content to determine regions of carbon deposition. It was found that only the tiles inboard of the inner strike point had appreciable 1 3 C above background. Visible spectroscopy measurements of the carbon injection and comparisons with modeling are consistent with carbon transport by means of scrape-off layer flow.
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| 124. |
- Baldo, B., et al.
(författare)
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SIRT1 is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease
- 2019
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 45:4, s. 361-379
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD. Methods: Quantitative real-time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno-associated viral vectors in mice. Results: We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in post mortem HD brains. Levels of SIRT2 are only increased in the striatum and SIRT3 is not affected in HD. Interestingly, mRNA levels of SIRT1 are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin-concentrating hormone (MCH) in the LHA and of brain-derived neurotrophic factor (BDNF) in the VMH. Analyses after selective hypothalamic expression of mutant HTT suggest that effects on BDNF, orexin, dynorphin and MCH are early and direct, whereas changes in SIRT1 require more widespread expression of mutant HTT. Conclusions: We show that SIRT1 expression is increased in HD-affected brain regions and that metabolic pathways are altered in the HD hypothalamus.
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| 125. |
- Barton, Nick, et al.
(författare)
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New insights into the late Middle Stone Age occupation of Oued elAkarit, southern Tunisia
- 2021
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Ingår i: Libyan Studies. - : Cambridge University Press. - 0263-7189 .- 2052-6148. ; 52, s. 12-35
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Tidskriftsartikel (refereegranskat)abstract
- This article reports on a new project to investigate the activities of early Homo sapiens in the area of the Chotts ‘megalake’ in southernTunisia. Excavations in 2015 and 2019 at Oued el Akarit revealed one of a number of Middle Stone Age (MSA) horizons near the topof a long sequence of Upper Pleistocene deposits. The site identified as Oued el Akarit (Sondage 8) consists of lithic artefacts, bone fragmentsof large ungulates and pieces of ostrich eggshell. Many of the objects are burnt. Excavation of about nine square metres revealed thatthese were associated with a lightly trampled and combusted occupation surface. Amongst the identified artefacts were Levallois flakes someof which could be refitted, thereby indicating the generally undisturbed nature of the occupation. The lithic finds also included side scrapersand other tools diagnostic of the MSA but significantly no bifacial or tanged tools. OSL (Optically Stimulated Luminescence) dating of thesediments and AMS (Accelerator Mass Spectrometry) radiocarbon dating of ostrich eggshell have produced uncalibrated age determinationsin the range 37,000–40,000 years ago, one of the youngest ages for MSA sites in the region. This is the first example of a securely dated laterMSA occupation in a riparian environment in south-eastern Tunisia
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| 126. |
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| 127. |
- Bykov, I., et al.
(författare)
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Modification of adhered dust on plasma-facing surfaces due to exposure to ELMy H-mode plasma in DIII-D
- 2017
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Ingår i: NUCLEAR MATERIALS AND ENERGY. - : Elsevier BV. - 2352-1791. ; 12, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Transient heat load tests have been conducted in the lower divertor of DIII-D using DiMES manipulator in order to study the behavior of dust on tungsten Plasma Facing Components (PFCs) during ELMy H-mode discharges. Samples with pre- adhered, pre- characterized dust have been exposed at the outer strike point (OSP) in a series of discharges with varied intra-(inter-) ELM heat fluxes. We used C dust because of its high sublimation temperature and non-metal properties. Al dust as a surrogate for Be and W dust were employed as relevant to that in the ITER divertor. The poor initial thermal contact between the substrate and the particles led to overheating, sublimation and shrinking of the carbon dust, and wetting induced coagulation of Al dust. Little modification of the W dust was observed. An enhanced surface adhesion and improvement of the thermal contact of C and Al dust were the result of exposure. A post mortem "adhesive tape" sampling showed that 70% of Al, <5% of W and C particles could not be removed from the surface owing to the improved adhesion. Al and C but not W particles that could be lifted had W inclusions indicating damage to the substrate. This suggests that non destructive methods may be inefficient for removal of dust in ITER.
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| 128. |
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| 129. |
- Eriksson, Py Liv, 1986, et al.
(författare)
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Ta Det Onda Med Det Goda (Accepting the Bad that Comes with the Good) - A Cultural Framework for Identity Narratives of Difficult Experiences in Sweden
- 2020
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Ingår i: Identity. An International Journal of Theory and Research. - : Informa UK Limited. - 1528-3488 .- 1532-706X. ; 20:3, s. 157-169
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the nature of narrating experiences of difficult life events among Swedish young adults. We use the master narrative cultural framework to understand how narratives of difficult experiences are told. Building on extant work on the importance of the narration of difficult life events for identity and wellbeing, we examine how these stories are narrated in the Swedish context in relation to well-being. Identity narratives about life challenges were collected from 116 participants (Mage = 33.28, SD = .54, n = 58 women). Employing an open-exploratory approach, four equally prevalent emotional sequences were found: redemptive sequencing, neutral/vague sequencing, a combination of positive and negative sequencing, and negative sequencing. No differences were found in the use of the first three emotional sequences for well-being, but the negative sequencing was generally associated with poorer well-being. This study shows that there are several ways to narrate difficult experiences in the Swedish context, and sheds light on how culture informs narrative identity.
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| 130. |
- Gross, Sean M., et al.
(författare)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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