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- Andersson, Anders G., et al.
(author)
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Effect of spatial resolution of rough surfaces on numerically computed flow fields with application to hydraulic engineering
- 2014
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In: Engineering Applications of Computational Fluid Mechanics. - : Informa UK Limited. - 1994-2060 .- 1997-003X. ; 8:3, s. 373-381
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Journal article (peer-reviewed)abstract
- In numerical simulations of flow over rough surfaces, the roughness is often not resolved but represented by a numerical model. The validity of such an assumption is investigated in this paper by Reynolds-Averaged Navier-Stokes simulations of flow over a surface with a large roughness. The surface was created from a high-resolution laser scanning of a real rock blasted tunnel. By reducing the geometrical resolution of the roughness in two steps, the importance of an appropriate surface description could be examined. The flow fields obtained were compared to a set-up with a geometrical flat surface where the roughness was represented by a modified form of the Launder and Spalding wall-function. The flow field over the surface with the lowest resolution was substantially different from those of the two finer resolutions and rather close to the results from the set-up with the wall-function. The results also yield that the finer the resolution is the more vorticity is formed close to the rough surface and more turbulence is generated.
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- Andersson, Daniel P., et al.
(author)
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Omentectomy in addition to gastric bypass surgery and influence on insulin sensitivity : A randomized double blind controlled trial
- 2014
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In: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 33:6, s. 991-996
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Journal article (peer-reviewed)abstract
- Background & aims: Accumulation of visceral adipose tissue is associated with insulin resistance and cardio-vascular disease. The aim of this study was to elucidate whether removal of a large amount of visceral fat by omentectomy in conjunction with Roux en-Y gastric bypass operation (RYGB) results in enhanced improvement of insulin sensitivity compared to gastric bypass surgery alone. Methods: Eighty-one obese women scheduled for RYGB were included in the study. They were randomized to RYGB or RYGB in conjunction with omentectomy. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp before operation and sixty-two women were also reexamined 2 years post-operatively. The primary outcome measure was insulin sensitivity and secondary outcome measures included cardio-metabolic risk factors. Results: Two-year weight loss was profound but unaffected by omentectomy. Before intervention, there were no clinical or metabolic differences between the two groups. The difference in primary outcome measure, insulin sensitivity, was not significant between the non-omentectomy (6.7 +/- 1.6 mg/kg body weight/minute) and omentectomy groups (6.6 +/- 1.5 mg/kg body weight/minute) after 2 years. Nor did any of the cardio-metabolic risk factors that were secondary outcome measures differ significantly. Conclusion: Addition of omentectomy to gastric bypass operation does not give an incremental effect on long term insulin sensitivity or cardio-metabolic risk factors. The clinical usefulness of omentectomy in addition to gastric bypass operation is highly questionable.
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- Englund, Gunilla, et al.
(author)
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Cytochrome P450 Inhibitory Properties of Common Efflux Transporter Inhibitors
- 2014
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In: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 42:3, s. 441-447
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Journal article (peer-reviewed)abstract
- Drug transporter inhibitors are important tools to elucidate the contribution of transporters to drug disposition both in vitro and in vivo. These inhibitors are often unselective and affect several transporters as well as drug metabolizing enzymes, which can make experimental results difficult to interpret with confidence. We therefore tested 14 commonly used P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance associated protein (MRP) inhibitors as inhibitors of cytochrome P450 (P450) enzyme activities using recombinant enzymes. A subset of P-gp and/or CYP3A inhibitors were selected (cyclosporin A, elacridar, ketoconazole, quinidine, reserpine, and tacrolimus) for a comparison of P450 inhibition in human microsomes and hepatocytes. Most P-gp inhibitors showed CYP3A4 inhibition, with potencies often in a similar range as their P-gp inhibition, as well as less potent CYP2C19 inhibition. Other P450 enzymes were not strongly inhibited except a few cases of CYP2D6 inhibition. MRP and BCRP inhibitors showed limited P450 inhibition. Some inhibitors showed less P450 inhibition in human hepatocytes than human liver microsomes, for example, elacridar, probably due to differences in binding, permeability limitations, or active, P-gp mediated efflux of the inhibitor from the hepatocytes. Quinidine was a potent P450 inhibitor in hepatocytes but only showed weak inhibition in microsomes. Quinidine shows an extensive cellular uptake, which may potentiate intracellular P450 inhibition. Elacridar, described as a potent and selective P-gp inhibitor, displayed modest P450 inhibition in this study and is thus a useful model inhibitor to define the role of P-gp in drug disposition without interference with other processes.
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- Gedefaw, Desta Antenehe, 1971, et al.
(author)
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Random polyfluorene co-polymers designed for a better optical absorption coverage of the visible region of the electromagnetic spectrum
- 2014
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In: Bulletin of the Chemical Society of Ethiopia. - : African Journals Online (AJOL). - 1726-801X .- 1011-3924. ; 28:1, s. 121-130
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Journal article (peer-reviewed)abstract
- Two alternating polyfluorenes (APFO15-F8BT and APFO3-F8BT) with full absorption of the visible region of the electromagnetic radiation were designed and synthesized for bulk-heterojunction solar cell devices. The optical and electrochemical properties of the two polymers were studied. The two polymers exhibited strong absorption in the visible region with no significant valley over the visible region extending up to 650 nm. Deep HOMO and ideally situated LUMO energy levels were the characteristics of the two polymers as revealed from the square wave voltammogram study: desired properties for extracting high open circuit voltage and for a facile charge transfer to the acceptor component in devices to take place, respectively. Photovoltaic devices were fabricated by blending the two polymers with PCBM[70] and up to similar to 2% power conversion efficiency were obtained.
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- Ghorbanzadeh, Mehdi, et al.
(author)
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In vitro and in silico derived relative effect potencies of Ah-Receptor-mediated effects by PCDD/Fs and PCBs in rat, mouse, and guinea pig CALUX Cell Lines
- 2014
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In: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 27:7, s. 1120-1132
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Journal article (peer-reviewed)abstract
- For a better understanding of species-specific relative effect potencies (REPs), responses of dioxin-like compounds (DLCs) were assessed. REPs were calculated using chemical-activated luciferase gene expression assays (CALUX) derived from guinea pig, rat, and mouse cell lines. Almost all 20 congeners tested in the rodent cell lines were partial agonists and less efficacious than 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For this reason, REPs were calculated for each congener using concentrations at which 20% of the maximal TCDD response was reached,(REP20TCDD). REP20TCDD values obtained for PCDD/Fs were comparable with their toxic equivalency factors assigned by the World Health Organization (WHO-TEF), while those for PCBs were in general lower than the WHO-TEF values. Moreover, the guinea pig cell line was the most sensitive as indicated by the 20% effect concentrations of TCDD of 1.5, 5.6, and 11.0 pM for guinea pig, rat, and mouse cells, respectively. A similar response pattern was observed using multivariate statistical analysis between the three CALLTX assays and the WHO-TEFs. The mouse assay showed minor deviation due to higher relative induction potential for 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,6,7,8-hexachlorodibenzofuran and lower for 1,2,3,4,6,7,8-heptachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphenyl (PCB126). 2,3,7,8-Tetrachlorodibenzofuran was more than two times more potent in the mouse assay as compared with that of rat and guinea pig cells, while measured REP20TCDD for PCB126 was lower in mouse cells (0.05) as compared with that of the guinea pig (0.2) and rat (0.07). In order to provide REP20TCDD values for all WHO-TEF assigned compounds, quantitative structure activity relationship (QSAR) models were developed. The QSAR models showed that specific electronic properties and molecular surface characteristics play important roles in the AhR-mediated response. In silica derived REP20TCDD values were generally consistent with the WHO-TEFs with a few exceptions. The QSAR models indicated that, e.g., 1,2,3,7,8-pentachlorodibenzofuran and 1,2,3,7,8,9-hexachlorodibenzofuran were more potent than given by their assigned WHO-TEF values, and the non-ortho PCB 81 was predicted, based on the guinea-pig model, to be 1 order of magnitude above its WHO-TEF value. By combining in vitro and in silico approaches, REPs were established for all WHO-TEF assigned compounds (except OCDD), which will provide future guidance in testing AhR-mediated responses of DLCs and to increase our understanding of species variation in AhR-mediated effects.
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- Hedström, Svante, et al.
(author)
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Light-harvesting capabilities of low band gap donor-acceptor polymers
- 2014
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In: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 16:45, s. 24853-24865
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Journal article (peer-reviewed)abstract
- A series of nine donor-acceptor polymers, including three new and six polymers from previous work, have been investigated experimentally and theoretically. The investigation focuses on narrow band gaps and strong absorptions of the polymers, where experimentally determined first peak absorption energies range from 1.8 to 2.3 eV, and peak absorption coefficients vary between 19-67 L g(-1) cm(-1). An overall assessment of each polymer's light-harvesting capability is made, and related to the chemical structure. Oligomer calculations using density functional theory are extrapolated to obtain size-converged polymer properties, and found to reproduce the experimental absorption trends well. Accurate theoretical predictions of absorption energies to within 0.06 eV of experiments, and absorption strength to within 12%, are obtained through the introduction of an empirical correction scheme. The computational and experimental results provide insight for the design of polymers with efficient absorption, concerning the intrinsic properties of the constituent units and the use of bulky side-groups.
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9. |
- Henriksson, Patrik, 1983, et al.
(author)
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Stability study of quinoxaline and pyrido pyrazine based co-polymers for solar cell applications
- 2014
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In: Solar Energy Materials and Solar Cells. - : Elsevier BV. - 0927-0248 .- 1879-3398. ; 130, s. 138-143
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Journal article (peer-reviewed)abstract
- We present two co-polymer families; one based on a thiophene-quinoxaline unit and one on a thiophene-pyrido pyrazine unit. Co-polymerization of these monomers with thiophene-hexylthiophene was performed to create polymers with an optical absorption that fully covers the visible part of the solar spectrum with the aim to enhance the solar cell performances of these polymers. We have also studied how increasing the fraction of thiophene-hexylthiophene affects the photo-oxidative stability of these polymers. Thiophene-pyrido pyrazine solar cells displayed increased device efficiency upon addition of the thiophene-hexylthiophene and, in addition, the stability is retained upon inclusion of these units. In contrast, we found that for the thiophene-quinoxaline based co-polymer, both device efficiency and stability decreased with increasing thiophene-hexylthiophene fraction. Moreover, our results indicate that the photo-oxidative stability of the thiophene-quinoxaline co-polymer is independent of the polymer molecular weight as well as of the film thickness.
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10. |
- Ji, Hong, et al.
(author)
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TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
- 2014
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In: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 5:4944
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Journal article (peer-reviewed)abstract
- Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-alpha markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-alpha-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-alpha-induced lymphangiogenesis. Moreover, TNF-alpha-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-alpha-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages in Tnfr1(+/+) mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-alpha-TNFR1 pathway.
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