| 1. |
- Isaksson, Rebecka, et al.
(författare)
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A Series of Analogues to the AT2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode
- 2019
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 8:1, s. 114-125
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Tidskriftsartikel (refereegranskat)abstract
- We here report on our continued studies of ligands binding tothe promising drug target angiotensin II type 2 receptor (AT2R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide AT2R antagonist C38, generating small but significant shifts in AT2R affinity. One compound in the first series was equipotent to C38 and showed similar kinetic solubility, and stability in both human and mouse liver microsomes. The second series was comprised of new bicyclic derivatives, amongst which one ligand exhibited a five-fold improved affinity to AT2R ascompared to C38. The majority of the compounds in the second series, including the most potent ligand, were inferior to C38 with regard to stability in both human and mouse microsomes. In contrast to our previously reported findings, ligands with shorter carbamate alkyl chains only demonstrated slightly improved stability in microsomes. Based on data presented herein, a more adequate, tentative model of the binding modes of ligand analogues to the prototype AT2R antagonist C38 is proposed, as deduced from docking redefined by molecular dynamic simulations.
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| 2. |
- Kero, Johan, et al.
(författare)
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Determination of meteoroid physical properties from tristatic radar observations
- 2008
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Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 26, s. 2217-2228
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Tidskriftsartikel (refereegranskat)abstract
- In this work we give a review of the meteor head echo observations carried out with the tristatic 930MHz EISCAT UHF radar system during four 24 h runs between 2002 and 2005 and compare these with earlier observations. A total number of 410 tristatic meteors were observed. We describe a method to determine the position of a compact radar target in the common volume monitored by the three receivers and demonstrate its applicability for meteor studies. The inferred positions of the meteor targets have been utilized to estimate their velocities, decelerations and directions of arrival as well as their radar cross sections with unprecedented accuracy. The velocity distribution of the meteoroids is bimodal with peaks at 35–40 km/s and 55–60 km/s, and ranges from 19–70 km/s. The estimated masses are between 10−9–10−5.5 kg. There are very few detections below 30 km/s. The observations are clearly biased to high-velocity meteoroids, but not so biased against slow meteoroids as has been presumed from previous tristatic measurements. Finally, we discuss how the radial deceleration observed with a monostatic radar depends on the meteoroid velocity and the angle between the trajectory and the beam. The finite beamwidth leads to underestimated meteoroid masses if radial velocity and deceleration of meteoroids approaching the radar are used as estimates of the true quantities in a momentum equation of motion.
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| 3. |
- Kero, Johan, et al.
(författare)
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On the meteoric head echo radar cross section angular dependence
- 2008
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 35, s. 5-
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Tidskriftsartikel (refereegranskat)abstract
- We present radar cross section (RCS) measurements of meteor head echoes observed with the tristatic 930 MHz EISCAT UHF radar system. The three receivers offer a unique possibility to accurately compare the monostatic RCS of a meteor target with two simultaneously probed bistatic RCSs at different aspect angles. Meteoroids from all possible directions entering the common volume monitored by the three receivers are detected, out to an aspect angle of 130° from the meteoroid trajectories. The RCS of individual meteors as observed by the three receivers are equal within the accuracy of the measurements. This is consistent with an essentially isotropic scattering process as has previously been inferred from polarization measurements by S. Close et al. (2002). There is a very weak trend present in our data suggesting that the RCS may decrease at a rate of 0.2 dB per 10° with increasing aspect angle.
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| 4. |
- Kero, Johan, et al.
(författare)
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Power fluctuations in meteor head echoes observed with the EISCAT VHF radar
- 2004
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Ingår i: Earth, moon, and planets. - : Springer Science and Business Media LLC. - 0167-9295 .- 1573-0794. ; 95:1-4, s. 633-638
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Tidskriftsartikel (refereegranskat)abstract
- We present observations and preliminary results from a meteor experiment carried out with the 224 MHz EISCAT VHF radar in Tromsø, Norway, which was run for 6 h on November 26, 2003. The data set contains echoes with peculiar pulsations in received power in the frequency range 20–200 Hz, limited by instrumental parameters. The process causing the echo power pulsations has not yet been identified. Plasma effects are the most likely cause, a possible mechanism is for instance asymmetrical dust grains in rotation causing a modulation of the ionization rate.
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| 5. |
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| 6. |
- Kero, Johan, et al.
(författare)
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Three-dimensional radar observation of a submillimeter meteoroid fragmentation
- 2008
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 35, s. 5-
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Tidskriftsartikel (refereegranskat)abstract
- We present and discuss two examples of pulsating meteor events observed with the tristatic 930 MHz EISCAT UHF radar system. One of them provides the first strong observational evidence of a submillimeter-sized meteoroid breaking apart into two distinct fragments. The received power fluctuates regularly in the time profiles of all three receivers, but the fluctuation frequencies are different. The pulsations are interpreted as being due to interference from two distinct scattering centers and the three detected pulsation rates are utilized to calculate the differential velocity of the fragments. The result is consistent with interference from two fragments of unequal cross-sectional area over mass ratio, separating from each other due to different deceleration along the trajectory of their parent meteoroid. The other meteor event is an example of a meteoroid undergoing quasi-continuous disintegration. This manifests itself as simultaneous pulsations at all three receivers. Both observations indicate a head echo target upper size limit of the order of half the 32 cm radar wavelength.
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| 7. |
- Larsson, Karin, et al.
(författare)
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Biological characterization of new inhibitors of microsomal PGE synthase-1 in preclinical models of inflammation and vascular tone
- 2019
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 176:24, s. 4625-4638
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Microsomal PGE synthase-1 (mPGES-1), the inducible synthase that catalyses the terminal step in PGE(2) biosynthesis, is of high interest as therapeutic target to treat inflammation. Inhibition of mPGES-1 is suggested to be safer than traditional NSAIDs, and recent data demonstrate anti-constrictive effects on vascular tone, indicating new therapeutic opportunities. However, there is a lack of potent mPGES-1 inhibitors lacking interspecies differences for conducting in vivo studies in relevant preclinical disease models. Experimental Approach Potency was determined based on the reduction of PGE(2) formation in recombinant enzyme assays, cellular assay, human whole blood assay, and air pouch mouse model. Anti-inflammatory properties were assessed by acute paw swelling in a paw oedema rat model. Effect on vascular tone was determined with human ex vivo wire myography. Key Results We report five new mPGES-1 inhibitors (named 934, 117, 118, 322, and 323) that selectively inhibit recombinant human and rat mPGES-1 with IC50 values of 10-29 and 67-250 nM respectively. The compounds inhibited PGE(2) production in a cellular assay (IC50 values 0.15-0.82 mu M) and in a human whole blood assay (IC50 values 3.3-8.7 mu M). Moreover, the compounds blocked PGE(2) formation in an air pouch mouse model and reduced acute paw swelling in a paw oedema rat model. Human ex vivo wire myography analysis showed reduced adrenergic vasoconstriction after incubation with the compounds. Conclusion and Implications These mPGES-1 inhibitors can be used as refined tools in further investigations of the role of mPGES-1 in inflammation and microvascular disease.
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| 8. |
- Pellinen-Wannberg, Asta, et al.
(författare)
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The impact of high resolution radar on meteor studies: the EISCAT perspective
- 2008
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Ingår i: URSI Radio Science Bulletin. - 1024-4530. ; :324, s. 17-28
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Tidskriftsartikel (refereegranskat)abstract
- Meteors, i.e. meteoroids interacting with the atmosphere, provided a vast amount of knowledge about interplanetary matter already long before the space era. Using what is today known as specular meteor radars (SMR), a great body of data on meteors was accumulated, mainly through recording echoes from the meteor trails. However, due to the specularity requirement and the ceiling effect, this method only detects a subset of the meteor population. By contrast, the High Power Large Aperture (HPLA) radar method can observe head echoes from meteors passing through the radar beam at almost arbitrary aspect angles. The very high power densities available at typical HPLA installations allow millisecond time resolution and spatial resolution in the range of tens of meters to be achieved routinely. In special cases, interference between echoes from two meteors has made it possible to achieve centimetre scale spatial resolution, thus allowing the deduction of an upper limit on the effective target size. Vector quantities such as meteor velocity and deceleration, providing mass and orbit estimates, can be recorded by phased arrays with interferometric capability, as well as by multi-static radars. A case in point is the tri-static EISCAT UHF radar system, which provides a unique capability of monitoring head echoes over a very wide range of aspect angles. A recent analysis of data from the UHF system confirms that head echo targets are essentially spherical in the forward direction. The next generation of HPLA systems is exemplified by the EISCAT_3D multistatic phased array radar concept. We discuss how this system will affect temporal and spatial resolution, sensitivity and rate of statistics in meteor observations.
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| 9. |
- Szasz, Csilla, et al.
(författare)
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Estimated visual magnitudes of the EISCAT UHF meteors
- 2008
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Ingår i: Advances in Meteoroid and Meteor Science. - New York, NY : Springer. - 9780387784182 ; , s. 373-378
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Bokkapitel (populärvet., debatt m.m.)abstract
- We have investigated the conditions for simultaneous meteor observations with the EISCAT UHF radar system and telescopic optical devices. The observed characteristics of 410 meteors detected by all three UHF receivers are compared with model simulations and their luminosity is calculated as a part of a meteoroid ablation model using a fifth order Runge–Kutta numerical integration technique. The estimated absolute visual magnitudes are in the range of +9 to +5. The meteors should therefore be observable using intensified CCD or EMCCD (Electron Multiplying CCD) cameras with telephoto lenses. A possible setup of a coordinated radar and optical campaign is suggested.
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| 10. |
- Szasz, Csilla, et al.
(författare)
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Estimated visual magnitudes of the EISCAT UHF meteors
- 2008
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Ingår i: Earth, moon, and planets. - : Springer Science and Business Media LLC. - 0167-9295 .- 1573-0794. ; 102:1-4, s. 373-378
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the conditions for simultaneous meteor observations with the EISCAT UHF radar system and telescopic optical devices. The observed characteristics of 410 meteors detected by all three UHF receivers are compared with model simulations and their luminosity is calculated as a part of a meteoroid ablation model using a fifth order Runge–Kutta numerical integration technique. The estimated absolute visual magnitudes are in the range of +9 to +5. The meteors should therefore be observable using intensified CCD or EMCCD (Electron Multiplying CCD) cameras with telephoto lenses. A possible setup of a coordinated radar and optical campaign is suggested.
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