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  • Zeisig, E, et al. (författare)
  • Akut behandling av hälseneruptur
  • 2018
  • Ingår i: Svensk IdrottsMedicin nr 3. - 1103-7652. ; :3, s. 17-19
  • Tidskriftsartikel (övrigt vetenskapligt)
  • Zetterberg, Fredrik R., et al. (författare)
  • Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-π, and Halogen Bond Interactions
  • 2018
  • Ingår i: ChemMedChem. - : Wiley-Blackwell. - 1860-7179. ; 13:2, s. 133-137
  • Tidskriftsartikel (refereegranskat)abstract
    • The design of small and high-affinity lectin inhibitors remains a major challenge because the natural ligand binding sites of lectin are often shallow and have polar character. Herein we report that derivatizing galactose with un-natural structural elements that form multiple non-natural lectin-ligand interactions (orthogonal multipolar fluorine-amide, phenyl-arginine, sulfur-π, and halogen bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the model lectin, galectin-3, which is more than five orders of magnitude higher than the parent galactose; moreover, is selective over other galectins.
  • Zettervall, N., et al. (författare)
  • A reduced chemical kinetic reaction mechanism for kerosene-air combustion
  • 2020
  • Ingår i: Fuel. - : Elsevier. - 0016-2361. ; 269
  • Tidskriftsartikel (refereegranskat)abstract
    • Development of a new reduced chemical kinetic reaction mechanism for kerosene-air combustion is presented. The new mechanism uses a modular based development technique and is a further development on previously presented kerosene-air mechanisms. The new mechanism consists of 30 species and 77 irreversible reactions and is developed to accurate reproduce key flame parameters yet being small enough to be used in finite rate Large Eddy Simulations (LES), Direct Numerical Simulations (DNS) and in Reynolds Average Navier-Stokes (RANS) simulations. The well-proven development technique uses a refined fuel breakdown oxidation sub-mechanism, a simplified C2 intermediate species sub-mechanism and a more detailed set of reactions for the H/C1/O chemistry. The mechanism has been modified to be able to predict ignition delay times for a wide range of temperatures, including in the negative temperature regime. The mechanism has been evaluated for combustion parameters related to flame propagation and ignition over a wide range of equivalence ratios, initial gas temperatures and pressures. Agreements to experimental data and a set of detailed and skeletal mechanisms are good for all target parameters. The proposed mechanism shows good agreement at a computational cost far below all tested reference mechanisms, making it highly suitable for use in combustion computational fluid dynamic (CFD) simulations.
  • Zettervall, N., et al. (författare)
  • Large Eddy Simulation of a premixed bluff body stabilized flame using global and skeletal reaction mechanisms
  • 2017
  • Ingår i: Combustion and Flame. - : Elsevier. - 0010-2180. ; 179, s. 1-22
  • Tidskriftsartikel (refereegranskat)abstract
    • The increasing computational capacity in recent years has spurred the growing use of combustion Large Eddy Simulation (LES) for engineering applications. The modeling of the subgrid stress and flux terms is well-established in LES, whereas the modeling of the filtered reaction rate terms is under intense development. The significance of the reaction mechanism is well documented, but only a few computational studies have so far been conducted with the aim of studying the influence of the reaction mechanism on the predicted flow and flame. Such an investigation requires the availability of well documented, thoroughly tested, and accurate reaction mechanisms suitable for use in practical engineering simulations. Global and detailed reaction mechanisms are available for many fuel mixtures, whereas skeletal reaction mechanisms suitable for LES are in rather short supply. This research attempts to close this gap by using combustion LES to examine a well-known bluff-body stabilized premixed propane–air flame using two well-known global reaction mechanisms and a novel skeletal reaction mechanism, developed as part of this study. These reaction mechanisms are studied for laminar flames, and comparison with experimental data and detailed reaction mechanisms demonstrates that the skeletal mechanism shows improved agreement with respect to all parameters studied, in particular the laminar flame speed and the extinction strain rate. The LES results reveal that the choice of the reaction mechanism does not significantly influence the instantaneous or time-averaged velocity, whereas the instantaneous and time-averaged species and temperature are influenced. The agreement with the experimental data increases with increased fidelity of the reaction mechanism, and the skeletal reaction mechanism provides a more realistic basis for e.g. emission predictions.
  • Zettervall, N., et al. (författare)
  • Small Skeletal Kinetic Mechanism for Kerosene Combustion
  • 2016
  • Ingår i: Energy and Fuels. - : The American Chemical Society (ACS). - 0887-0624. ; 30:11, s. 9801-9813
  • Tidskriftsartikel (refereegranskat)abstract
    • The development and validation of a new skeletal mechanism for kerosene combustion, suitable for reacting direct-, large-eddy, and Reynolds averaged Navier-Stokes Simulations, are presented. The mechanism consists of 65 irreversible reactions between 22 species and is built on a global fuel breakdown approach to produce a subset of C2 intermediates. A more detailed set of reactions for H/O/C1 chemistry largely determines the combustion characteristics. The mechanism is validated for combustion characteristics related to ignition, flame propagation, and flame extinction over a wide range of pressure, temperature, and equivalence ratios. Agreement with experiments and a more complex reference mechanism are excellent for laminar burning velocities and extinction strain rate, while ignition delays are overpredicted at stoichiometric and rich conditions. Concentration profiles for major stable products are in agreement with reference mechanism, and also a range of intermediate species and radicals shows sufficient agreement. The skeletal mechanism shows an overall good performance in combination with a numerical stability and short computation time, making it highly suitable for combustion Large Eddy Simulation (LES).
  • Zhang, Xiaoqun, et al. (författare)
  • Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or beta-Phenylethylamine
  • 2018
  • Ingår i: Frontiers in Pharmacology. - : FRONTIERS MEDIA SA. - 1663-9812 .- 1663-9812. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (beta-PEA) compared to 3-iodothyronamine (T(1)AM). Immunoblotting and amperometry were performed in dorsal striatal slices from wildtype (WT) and TAAR1 knockout (KO) mice. T(1)AM increased TH phosphorylation at both Ser(19) and Ser(40), actions that should promote functional activity of TH. Indeed, HPLC data revealed higher rates of L-dihydroxyphenylalanine (DOPA) accumulation in WT animals treated with T(1)AM after the administration of a DOPA decarboxylase inhibitor. These effects were abolished both in TAAR1 KO mice and by the TAAR1 antagonist, EPPTB. Further, they were specific inasmuch as Ser(845) phosphorylation of the post-synaptic GluA1 AMPAR subunit was unaffected. The effects of T1AM on TH phosphorylation at both Ser(19) (CamKII-targeted), and Ser40 (PKA-phosphorylated) were inhibited by KN-92 and H-89, inhibitors of CamKII and PKA respectively. Conversely, there was no effect of an EPAC analog, 8-CPT-2Me-cAMP, on TH phosphorylation. In line with these data, T(1)AM increased evoked striatal dopamine release in TAAR1 WT mice, an action blunted in TAAR1 KO mice and by EPPTB. Mass spectrometry imaging revealed no endogenous T(1)AM in the brain, but detected T(1)AM in several brain areas upon systemic administration in both WT and TAAR1 KO mice. In contrast to T1AM, tyramine decreased the phosphorylation of Ser40-TH, while increasing Ser(845)-GluA1 phosphorylation, actions that were not blocked in TAAR1 KO mice. Likewise, beta-PEA reduced Ser(40)-TH and tended to promote Ser845-GluA1 phosphorylation. The D-1 receptor antagonist SCH23390 blocked tyramine-induced Ser(845)-GluA1 phosphorylation, but had no effect on tyramine-or beta-PEA-induced Ser(40)-TH phosphorylation. In conclusion, by intracellular cascades involving CaMKII and PKA, T(1)AM, but not tyramine and beta-PEA, acts via TAAR1 to promote the phosphorylation and functional activity of TH in the dorsal striatum, supporting a modulatory influence on dopamine transmission.
  • Zhao, Ming, et al. (författare)
  • FcgammaRIIB inhibits the development of atherosclerosis in low-density lipoprotein receptor-deficient mice
  • 2010
  • Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 184:5, s. 2253-2260
  • Tidskriftsartikel (refereegranskat)abstract
    • The immune processes associated with atherogenesis have received considerable attention during recent years. IgG FcRs (FcgammaR) are involved in activating the immune system and in maintaining peripheral tolerance. However, the role of the inhibitory IgG receptor FcgammaRIIB in atherosclerosis has not been defined. Bone marrow cells from FcgammaRIIB-deficient mice and C57BL/6 control mice were transplanted to low-density lipoprotein receptor-deficient mice. Atherosclerosis was induced by feeding the recipient mice a high-fat diet for 8 wk and evaluated using Oil Red O staining of the descending aorta at sacrifice. The molecular mechanisms triggering atherosclerosis was studied by examining splenic B and T cells, as well as Th1 and Th2 immune responses using flow cytometry and ELISA. The atherosclerotic lesion area in the descending aorta was ~5-fold larger in mice lacking FcgammaRIIB than in control mice (2.75 +/- 2.57 versus 0.44 +/- 0.42%; p < 0.01). Moreover, the FcgammaRIIB deficiency resulted in an amplified splenocyte proliferative response to Con A stimulation (proliferation index 30.26 +/- 8.81 versus 2.96 +/- 0.81%, p < 0.0001) and an enhanced expression of MHC class II on the B cells (6.65 +/- 0.64 versus 2.33 +/- 0.25%; p < 0.001). In accordance, an enlarged amount of CD25-positive CD4 T cells was found in the spleen (42.74 +/- 4.05 versus 2.45 +/- 0.31%; p < 0.0001). The plasma Ab and cytokine pattern suggested increased Th1 and Th2 immune responses, respectively. These results show that FcgammaRIIB inhibits the development of atherosclerosis in mice. In addition, they indicate that absence of the inhibiting IgG receptor cause disease, depending on an imbalance of activating and inhibiting immune cells.
  • Zhao, Q, et al. (författare)
  • Conjugate chemistry, iodination and cellular binding of mEGF-dextran-tyrosine: preclinical tests in preparation for clinicaltrials
  • 1998
  • Ingår i: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 1:4, s. 693-702
  • Tidskriftsartikel (refereegranskat)abstract
    • A conjugate with specific binding to the epidermal growth factor receptor, EGFR, and of interest for clinical tests was prepared using mouse epidermal growth factor, mEGF, and dextran. The mEGF was first coupled to dextran by reductive amination in which the free amino group on the N-terminal of mEGF was reacted with the aldehyde group on the reductive end of the dextran chain. The end-end coupled intermediate was further activated by the cyanopyridinium agent CDAP and tyrosines introduced to the dextran part of the conjugate. The mEGF-dextran-tyrosine conjugate was, with high efficiency, iodinated with the chloramine-T method. Approximately 25-35% of the radioactivity could be removed from the conjugate after exposure to protease K while 65-75% of the radioactivity could be removed after exposure to dextranase. Thus, the largest amount of the iodine was on the dextran part of the conjugate. The iodinated mEGF-dextran-tyrosine had EGFR specific binding since the binding to an EGFR rich human glioma cell line could be displaced by an excess of non-radioactive mEGF. The conjugate was to a large extent internalized in these cells and the administrated radioactivity was thereby retained inside the cells for at least up to 50 h.
  • Zhao, Qian, et al. (författare)
  • Dissemination of bla(NDM-5) via IncX3 plasmids in carbapenem-resistant Enterobacteriaceae among humans and in the environment in an intensive vegetable cultivation area in eastern China
  • 2021
  • Ingår i: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 273
  • Tidskriftsartikel (refereegranskat)abstract
    • The environment of a large-scale vegetable production area can be exposed to antibiotic residues and antibiotic-resistant bacteria (ARB) via animal manure and irrigation with contaminated water, which can facilitate the dissemination of ARB. However, the occurrence of ARB in plantation areas and their dissemination in this environment remain largely unexplored. In total, 382 samples including those from vegetable (n = 106), soil (n = 87), well water (n = 24), river water (n = 20), river sediments (n = 20), farmer feces (n = 58) and farmer hands (n = 67) were collected in 2019 from a large-scale cultivation area in Shandong, China. Selective agar plates were used to screen for carbapenem-resistant Enterobacteriaceae (CRE) and whole-genome sequencing and Southern blotting were used to characterise isolates and mobile genetic elements carrying carbapenem resistance determinants. A total of nine NDM-5-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Citrobacter spp. were identified from environmental sources and human feces, all of which were multidrug-resistant. Single nucleotide polymorphism analysis suggested clonal transmission of carbapenem-resistant Citrobacter sedlakii within greenhouse soils in the area. Eight of the isolates carried closely related or identical IncX3 plasmids carrying bla(NDM-5), which were shown to be conjugative via filter mating experiments, indicating the highly transmissible nature of this genetic element. Isolates of E. coli and Citrobacter freundii were detected in the feces of local farm workers and contained similar IncX3 plasmids with bla(NDM-5) environmental isolates, suggesting a potential risk of CRE transfer from the work environment to the farm workers. Thus, further research is required to investigate the potential health risks associated with environmental exposure to CRE in vegetable cultivation areas. (C) 2020 Elsevier Ltd. All rights reserved.
  • Zheng, Ju-Sheng, et al. (författare)
  • Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes : EPIC-InterAct case-cohort study in eight European countries
  • 2020
  • Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 1756-1833. ; 370
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.Design: Prospective case-cohort study.Setting: Populations from eight European countries.Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measure: Incident type 2 diabetes.Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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