| 1. |
- Caraballo, Remi, et al.
(författare)
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Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
- 2015
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 103, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.
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| 2. |
- Ericsson, Per, et al.
(författare)
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Characterization of particulate emissions and methodology for oxidation of particulates from non-diesel combustion systems
- 2008
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Ingår i: SAE Technical Paper. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
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Tidskriftsartikel (refereegranskat)abstract
- Tailpipe particulate emissions, i.e., particle number, size distribution and total mass, from a series of four-cylinder engines with 2L displacement and power output of approximately 150 hp have been measured. The engines were in their respective vehicle installation, all midsize vehicles from various manufacturers, and represented different combustion concepts, i.e., port- and direct-injected vehicles and E5 and E85 fuels. The results are compared to post-Euro V emission standards for gasoline and biofuels using diesel as reference. The results show that the type of combustion and fuel significantly affect the particulate formation. In general, direct-injected engines show high particle numbers and mass compared to port-injected engines. The particulate number and total mass can be reduced by using biofuels, e.g., ethanol mixes, instead of gasoline. Moreover, an experimental procedure and setup facilitating precise studies of oxidation of particulates in realistic filter structures by well-controlled gas flow (composition and temperature) and sample (particulate load and temperature) conditions has been developed. The results from this method have been verified by using commercial soot as reference.
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| 4. |
- Ericsson, Peter, et al.
(författare)
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ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.
- 2003
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 93:2, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.
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| 5. |
- Forsberg, Fredrik, et al.
(författare)
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CMOS-integrated Si/SiGe quantum-well infrared microbolometer focal plane arrays manufactured with very large-scale heterogeneous 3-d integration
- 2015
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Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - : Institute of Electrical and Electronics Engineers Inc.. - 0792-1233 .- 1077-260X .- 1558-4542. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate infrared focal plane arrays utilizing monocrystalline silicon/silicon-germanium (Si/SiGe) quantum-well microbolometers that are heterogeneously integrated on top of CMOS-based electronic read-out integrated circuit substrates. The microbolometers are designed to detect light in the long wavelength infrared (LWIR) range from 8 to 14 μm and are arranged in focal plane arrays consisting of 384 × 288 microbolometer pixels with a pixel pitch of 25 μm × 25 μm. Focal plane arrays with two different microbolometer designs have been implemented. The first is a conventional single-layer microbolometer design and the second is an umbrella design in which the microbolometer legs are placed underneath the microbolometer membrane to achieve an improved pixel fill-factor. The infrared focal plane arrays are vacuum packaged using a CMOS compatible wafer bonding and sealing process. The demonstrated heterogeneous 3-D integration and packaging processes are implemented at wafer-level and enable independent optimization of the CMOS-based integrated circuits and the microbolometer materials. All manufacturing is done using standard semiconductor and MEMS processes, thus offering a generic approach for integrating CMOS-electronics with complex miniaturized transducer elements
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| 6. |
- Wang-Hansen, Carolin, 1982, et al.
(författare)
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Characterization of particulate matter from direct injected gasoline engines
- 2013
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Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 56:1-8, s. 446-451
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Tidskriftsartikel (refereegranskat)abstract
- The reactivity and reaction kinetics of particulate matter (PM) from direct injected gasoline (GDI) engines has been studied by O2 and NO2 based temperature programmed and isothermal step-response experiments, and the PM nano-structure has been characterized using HRTEM. The reactivity of the PM samples collected in filters during on-road driving was found to increase in the following order: Printex U\diesel\gasoline PI & gasoline DI\ethanol for O2 based combustion. The activation energies for O2 and NO2 based oxidation of PM collected from a GDI engine in an engine bench set-up was estimated to 146 and 71 kJ/mol respectively, which is comparable to corresponding values reported for diesel and model soot. Similar nano-structure features (crystallites plane dimensions, curvature and relative orientation) as observed for diesel soot were observed for gasoline PM.
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| 7. |
- Abdu, Yassir, et al.
(författare)
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Field induced local magnetic moments in gamma-fcc Fe-Ni anti-Invar alloys
- 2004
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Ingår i: Journal of Magnetism and Magnetic Materials. - 0304-8853 .- 1873-4766. ; 280, s. 243-250
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Tidskriftsartikel (refereegranskat)abstract
- Mössbauer spectroscopy in longitudinal external fields (up to 7 T) and SQUID magnetometry (up to 5 T)measurements have been carried out on mechanically alloyed (MA) g (FCC) Fe100xNix (x ¼ 21; 24, and 27 at%) alloysat room temperature. The zero-field M.ossbauer spectra of these alloys show only singlets. The high field M.ossbauerresults indicate that large amounts of the material is in the paramagnetic state, giving rise to two spectral componentswith their effective fields almost linearly depend on the external field, but with slopes that are smaller than unity. The infieldM.ossbauer spectra of the x ¼ 27 at% alloy show an additional component with a hyperfine field of E21 T, whichis attributed to Ni-rich (>30 at% Ni) clusters (domains) of ferromagnetically ordered HM phase that behavessuperparamagnetically at room temperature and shows a non-linear character in the magnetization (M–H) curves atlow fields. This HM phase is also present in the x ¼ 21 and 24 at% samples but with smaller amounts. The resultssuggest induced hyperfine fields and hence induced moments in the paramagnetic components, which increases withincreasing Ni contents. Taenite-enriched samples from the metal particles of two stony meteorites, Al Kidirate (H6)and New Halfa (L4), are also studied by high field M.ossbauer spectroscopy and the results are compared to that ofMA samples.
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