9 research outputs found
Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension
Prostacyclin
controls cardiovascular function via activation of the prostacyclin
receptor. Decreased prostacyclin production occurs in several cardiovascular
diseases. However, the clinical use of prostacyclin and its analogues
is complicated by their chemical and metabolic instability. A medicinal
chemistry program searched for novel nonprostanoid prostacyclin receptor
agonists not subject to these limitations. A compound with a diphenylpyrazine
structural core was synthesized. Metabolic stability and agonist potency
were optimized through modification of the linear side chain. Compound <b>12b</b> (MRE-269, ACT-333679) was identified as a potent and highly
selective prostacyclin receptor agonist. Replacement of the terminal
carboxyl group with an <i>N</i>-acylsulfonamide group yielded
parent compound <b>26a</b> (selexipag, NS-304, ACT-293987),
which is orally active and provides sustained plasma exposure of <b>12b</b>. Compound <b>26a</b> was developed for the treatment
of pulmonary arterial hypertension and shown to reduce the
risk of the composite morbidity/mortality end point in a phase 3 event-driven
clinical trial
Diagram describing structural characteristics of the tropical peat swamp forest that impact scattering signals and associated metrics included in this study (adapted from Kasischke and Bourgeau-Chavez [33]).
Diagram describing structural characteristics of the tropical peat swamp forest that impact scattering signals and associated metrics included in this study (adapted from Kasischke and Bourgeau-Chavez [33]).</p
Diagram depicting sources of scattering from inundated forests (adapted from Kasischke and Bourgeau-Chavez [33]).
Scattering mechanisms in bold represent scattering sources that result in interferometric fringes.</p
Photographs illustrating common land cover types and field conditions at north Selangor.
(a) secondary forest, (b) burned peatland with dense grass and shrubs, (c) rice paddy agriculture and (d) oil palm plantation. (Photo credits: MJL).</p
Fig 5 -
Maps presenting processed optical and LiDAR data, describing above-ground biomass structure and peat swamp surface characteristics, including (a) LAI (leaf area index per 20 m2); (b) LiDAR ground point density (ground point number per 10 m2); (c) ROUGH; (d) WD; (e) VDR. All LiDAR-derived datasets are limited to the LiDAR flight line coverage over North Selangor. Base map provided by OpenStreetMap®. OpenStreetMap® is open data, licensed under the Open Data Commons Open Database License (ODbL) by the OpenStreetMap Foundation (OSMF). OpenStreetMap® is made available under the Open Database License: http://opendatacommons.org/licenses/odbl/1.0/. Any rights in individual contents of the database are licensed under the Database Contents License: http://opendatacommons.org/licenses/dbcl/1.0/.</p
Fig 6 -
Sentinel-1 interferograms and coherence maps for North Selangor: a) VV polarisation from 2/7/2017 to 17/7/2017; b) VH polarisation from 2/7/2017 to 17/7/2017; c) VV polarisation from 14/8/2018 to 14/8/2018; d) the VH polarisation from 14/8/2018 to 14/8/2018. Base map provided by OpenStreetMap®. OpenStreetMap® is open data, licensed under the Open Data Commons Open Database License (ODbL) by the OpenStreetMap Foundation (OSMF). OpenStreetMap® is made available under the Open Database License: http://opendatacommons.org/licenses/odbl/1.0/. Any rights in individual contents of the database are licensed under the Database Contents License: http://opendatacommons.org/licenses/dbcl/1.0/.</p
PCA visualising the relationship between <i>coherence count</i> (cohcount) values and metrics describing the canopy, trunk and surface layers in the model of the above-ground biomass stand: LAI (canopy openness), ROUGH (canopy roughness), WD (height of forest stand), VDR (ratio of canopy layer to trunk layer) and GPD (exposure of peat swamp forest surface).
Plots represent all 2-dimensional combinations of the first three Principal Components: (a) PC1 and PC2, (b) PC1 and PC3, (c) PC2 and PC3. All three plots show that coherence count is orthogonal to all other variables.</p
Fig 7 -
(a) Map of coherence counts (cohcount) of interferometric pairs at 20 m resolution between 10/10/2014 and 29/04/2020. The coherence count represents the number of interferometric pairs that are above the coherence threshold of 0.45 (maximum = 1520). (b) Map of land cover for North Selangor. Study of both maps show that coherence counts remained high over forestry within North Selangor relative to other land cover types. Base map provided by OpenStreetMap®. OpenStreetMap® is open data, licensed under the Open Data Commons Open Database License (ODbL) by the OpenStreetMap Foundation (OSMF). OpenStreetMap® is made available under the Open Database License: http://opendatacommons.org/licenses/odbl/1.0/. Any rights in individual contents of the database are licensed under the Database Contents License: http://opendatacommons.org/licenses/dbcl/1.0/.</p
North Selangor reserve boundary and peatland extent located within Selangor, Peninsular Malaysia, SE Asia.
Base map provided by OpenStreetMap®. OpenStreetMap® is open data, licensed under the Open Data Commons Open Database License (ODbL) by the OpenStreetMap Foundation (OSMF). OpenStreetMap® is made available under the Open Database License: http://opendatacommons.org/licenses/odbl/1.0/. Any rights in individual contents of the database are licensed under the Database Contents License: http://opendatacommons.org/licenses/dbcl/1.0/.</p