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Sökning: WFRF:(Maxwell Taylor J.) > (2020-2022)

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  • Mailloux, J., et al. (författare)
  • Overview of JET results for optimising ITER operation
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
  • Forskningsöversikt (refereegranskat)abstract
    • The JET 2019-2020 scientific and technological programme exploited the results of years of concerted scientific and engineering work, including the ITER-like wall (ILW: Be wall and W divertor) installed in 2010, improved diagnostic capabilities now fully available, a major neutral beam injection upgrade providing record power in 2019-2020, and tested the technical and procedural preparation for safe operation with tritium. Research along three complementary axes yielded a wealth of new results. Firstly, the JET plasma programme delivered scenarios suitable for high fusion power and alpha particle (α) physics in the coming D-T campaign (DTE2), with record sustained neutron rates, as well as plasmas for clarifying the impact of isotope mass on plasma core, edge and plasma-wall interactions, and for ITER pre-fusion power operation. The efficacy of the newly installed shattered pellet injector for mitigating disruption forces and runaway electrons was demonstrated. Secondly, research on the consequences of long-term exposure to JET-ILW plasma was completed, with emphasis on wall damage and fuel retention, and with analyses of wall materials and dust particles that will help validate assumptions and codes for design and operation of ITER and DEMO. Thirdly, the nuclear technology programme aiming to deliver maximum technological return from operations in D, T and D-T benefited from the highest D-D neutron yield in years, securing results for validating radiation transport and activation codes, and nuclear data for ITER.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
  • Kang, E. Y., et al. (författare)
  • MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma
  • 2022
  • Ingår i: Virchows Archiv. - 0945-6317. ; 480
  • Tidskriftsartikel (refereegranskat)abstract
    • Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
  • Maxwell, Taylor J., et al. (författare)
  • Quantitative trait loci, G×E and G×G for glycemic traits : response to metformin and placebo in the Diabetes Prevention Program (DPP)
  • 2022
  • Ingår i: Journal of Human Genetics. - : Springer. - 1434-5161.
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex genetic architecture of type-2-diabetes (T2D) includes gene-by-environment (G×E) and gene-by-gene (G×G) interactions. To identify G×E and G×G, we screened markers for patterns indicative of interactions (relationship loci [rQTL] and variance heterogeneity loci [vQTL]). rQTL exist when the correlation between multiple traits varies by genotype and vQTL occur when the variance of a trait differs by genotype (potentially flagging G×G and G×E). In the metformin and placebo arms of the DPP (n = 1762) we screened 280,965 exomic and intergenic SNPs, for rQTL and vQTL patterns in association with year one changes from baseline in glycemia and related traits (insulinogenic index [IGI], insulin sensitivity index [ISI], fasting glucose and fasting insulin). Significant (p < 1.8 × 10−7) rQTL and vQTL generated a priori hypotheses of individual G×E tests for a SNP × metformin treatment interaction and secondarily for G×G screens. Several rQTL and vQTL identified led to 6 nominally significant (p < 0.05) metformin treatment × SNP interactions (4 for IGI, one insulin, and one glucose) and 12G×G interactions (all IGI) that exceeded experiment-wide significance (p < 4.1 × 10−9). Some loci are directly associated with incident diabetes, and others are rQTL and modify a trait’s relationship with diabetes (2 diabetes/glucose, 2 diabetes/insulin, 1 diabetes/IGI). rs3197999, an ISI/insulin rQTL, is a possible gene damaging missense mutation in MST1, a gene affecting β-cell apoptosis and insulin secretion. This rQTL may link MST1 with insulin sensitivity where ISI and insulin responses differentially vary by genotype. This study demonstrates evidence for context-dependent effects (G×G & G×E) and the complexity of these T2D-related traits.
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