| 1. |
- Boyajian, T., et al.
(författare)
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Stellar diameters and temperatures - VI. High angular resolution measurements of the transiting exoplanet host stars HD 189733 and HD 209458 and implications for models of cool dwarfs
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 447:1, s. 846-857
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Tidskriftsartikel (refereegranskat)abstract
- We present direct radii measurements of the well-known transiting exoplanet host stars HD 189733 and HD 209458 using the CHARA Array interferometer. We find the limb-darkened angular diameters to be thetaLD = 0.3848 +/- 0.0055 and 0.2254 +/- 0.0072 milliarcsec for HD 189733 and HD 209458, respectively. HD 189733 and HD 209458 are currently the only two transiting exoplanet systems where detection of the respective planetary companion's orbital motion from high resolution spectroscopy has revealed absolute masses for both star and planet. We use our new measurements together with the orbital information from radial velocity and photometric time series data, Hipparcos distances, and newly measured bolometric fluxes to determine the stellar effective temperatures (Teff = 4875 +/- 43, 6093 +/- 103 K), stellar linear radii (R* = 0.805 +/- 0.016, 1.203 +/- 0.061 Rsun), mean stellar densities (rho* = 1.62 +/- 0.11, 0.58 +/- 0.14 rhosun), planetary radii (Rp = 1.216 +/- 0.024, 1.451 +/- 0.074 RJup), and mean planetary densities (rhop = 0.605 +/- 0.029, 0.196 +/- 0.033 rhoJup) for HD 189733 b and HD 209458 b, respectively. The stellar parameters for HD 209458, a F9 dwarf, are consistent with indirect estimates derived from spectroscopic and evolutionary modeling. However, we find that models are unable to reproduce the observational results for the K2 dwarf, HD 189733. We show that, for stellar evolutionary models to match the observed stellar properties of HD 189733, adjustments lowering the solar-calibrated mixing length parameter from 1.83 to 1.34 need to be employed.
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| 2. |
- Cammareri, Patrizia, et al.
(författare)
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Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signalling, which is localized to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through Braf V600E or Kras G12D knockin) and TGFβ signalling ablation (through Tgfbr1 deletion) in LGR5 +ve stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5 +ve cells also results in cSCC development. These findings indicate that LGR5 +ve stem cells may act as cells of origin for cSCC, and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFβ signalling, are driving events of skin tumorigenesis.
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| 3. |
- Huels, David J., et al.
(författare)
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E-cadherin can limit the transforming properties of activating beta-catenin mutations
- 2015
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Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 34:18, s. 2321-2333
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Tidskriftsartikel (refereegranskat)abstract
- Wnt pathway deregulation is a common characteristic of many cancers. Only colorectal cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of the pancreas) have activating mutations in beta-catenin (CTNNB1). We have compared the dynamics and the potency of beta-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of beta-catenin took much longer to achieve Wnt deregulation and acquire a crypt-progenitor cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of beta-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of beta-catenin mutation to differentially transform the SI versus the colon correlated with higher expression of E-cadherin and a higher number of E-cadherin: beta-catenin complexes at the membrane. Reduction in E-cadherin synergised with an activating mutation of beta-catenin resulting in a rapid CPC phenotype within the SI and colon. Thus, there is a threshold of beta-catenin that is required to drive transformation, and E-cadherin can act as a buffer to sequester mutated beta-catenin.
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| 4. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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