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- Hawinkels, L J A C, et al.
(author)
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Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts
- 2014
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In: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 33:1, s. 97-107
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Journal article (peer-reviewed)abstract
- The interaction between epithelial cancer cells and cancer-associated fibroblasts (CAFs) has a major role in cancer progression and eventually in metastasis. In colorectal cancer (CRC), CAFs are present in high abundance, but their origin and functional interaction with epithelial tumor cells has not been elucidated. In this study we observed strong activation of the transforming growth factor-β (TGF-β)/Smad signaling pathway in CRC CAFs, accompanied by decreased signaling in epithelial tumor cells. We evaluated the TGF-β1 response and the expression of target genes including matrix metalloproteinases (MMPs) and plasminogen activator inhibitor (PAI)-1 of various epithelial CRC cell lines and primary CAFs in vitro. TGF-β1 stimulation caused high upregulation of MMPs, PAI-1 and TGF-β1 itself. Next we showed that incubation of CAFs with conditioned medium (CM) from epithelial cancer cells led to hyperactivation of the TGF-β signaling pathway, enhanced expression of target genes like PAI-1, and the expression of α-smooth muscle actin (α-SMA). We propose that the interaction of tumor cells with resident fibroblasts results in hyperactivated TGF-β1 signaling and subsequent transdifferentiation of the fibroblasts into α-SMA-positive CAFs. In turn this leads to cumulative production of TGF-β and proteinases within the tumor microenvironment, creating a cancer-promoting feedback loop.
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| 4. |
- Bryant, Fred B., et al.
(author)
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Confirmatory Factor Analysis of Ordinal Data Using Full-Information Adaptive Quadrature
- 2016
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In: Australian & New Zealand journal of statistics (Print). - : Wiley. - 1369-1473 .- 1467-842X. ; 58:2, s. 173-196
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Journal article (peer-reviewed)abstract
- We conducted confirmatory factor analysis (CFA) of responses (N=803) to a self-reported measure of optimism, using full-information estimation via adaptive quadrature (AQ), an alternative estimation method for ordinal data. We evaluated AQ results in terms of the number of iterations required to achieve convergence, model fit, parameter estimates, standard errors (SE), and statistical significance, across four link-functions (logit, probit, log-log, complimentary log-log) using 3-10 and 20 quadrature points. We compared AQ results with those obtained using maximum likelihood, robust maximum likelihood, and robust diagonally weighted least-squares estimation. Compared to the other two link-functions, logit and probit not only produced fit statistics, parameters estimates, SEs, and levels of significance that varied less across numbers of quadrature points, but also fitted the data better and provided larger completely standardised loadings than did maximum likelihood and diagonally weighted least-squares. Our findings demonstrate the viability of using full-information AQ to estimate CFA models with real-world ordinal data.
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| 5. |
- Barbe, Laure, et al.
(author)
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Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection
- 2018
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Journal article (peer-reviewed)abstract
- Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAc beta 3Gal beta 4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
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| 9. |
- Gaiotti, Marco, et al.
(author)
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A numerical sensitivity analysis on the cohesive parameters of a carbon-steel single lap joint
- 2020
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In: Ocean Engineering. - : Elsevier BV. - 0029-8018. ; 198
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Journal article (peer-reviewed)abstract
- One of the key issues concerning the use of composite materials in the construction of steel ships, or vice versa, the use of steel in the construction of composite ships, is related to the ways of joining composite parts to the adjacent steel structure. Carbon-steel joints are of increasing interest for the maritime industry, but knowledge is scarce. Applications of adhesive joints as an alternative method to welding or riveting has numerous advantages. Still, gathering more information about the behaviour of such joints through numerical sensitivity analysis and simulation are necessary to speed up applications on ships and marine structures. The present investigation aims at assessing the sensitivity of the parameters that define the traction separation law on the numerical simulation of the de-bonding of a steel to composite single lap joint, following a previous experimental campaign. The test is intended to induce a mode II separation, although the slight bending moment caused by the misalignment of the two ends leads to mixed mode effects, as well. Two finite element software were compared, ADINA and LS-DYNA. The influence of peak traction, penalty stiffness and energy release rate were investigated, along with the effect of a mixed mode opening behaviour.
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| 10. |
- Vorobiev, Andrei, 1963, et al.
(author)
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Composite Ferroelectric FBARs That Are Switchable Between the First and Second Harmonics: Experimental Demonstration
- 2015
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In: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. - : Institute of Electrical and Electronics Engineers (IEEE). - 0885-3010. ; 62:3, s. 565-575
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Journal article (peer-reviewed)abstract
- Digital switching between the first and second harmonics, in a composite thin-film bulk acoustic wave resonator (FBAR), is demonstrated experimentally. The FBAR consists of two 180-nm-thick paraelectric-phase Ba0.25Sr0.75TiO3 films separated by a 50-nm-thick SrRuO3 conducting layer. The resonant frequency of this composite resonator (with Pt bottom and Al top electrodes) is switched from 3.6 GHz to 7.6 GHz, where the polarity of the 5 V dc bias is reversed on one of the ferroelectric films. The frequency switching ratio (f(2)/f(1) >= 2) depends on the thickness of the electrodes. Some adjustment of f(2)/f(1) is possible by changing the applied dc bias.
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