Nestorone® as a Novel Progestin for Nonoral Contraception:Structure-Activity Relationships and Brain Metabolism Studies

Nestorone® (NES) is a highly potent non-androgenic progestin being developed for contraception. NES is a synthetic progestin that may possess neuroprotective and myelin regenerative potential as an added health benefits. In receptor transactivation experiments, NES displayed greater potency than progesterone to transactivate the human progesterone receptor (hPR). This was confirmed by docking experiments which revealed that NES adopts the same docking position within the PR ligand-binding domain (LBD) as progesterone and forms additional stabilizing contacts between 17α-acetoxy and 16-methylene groups and PR LBD supporting its higher potency than progesterone. The analogue 13-ethyl NES also establishes similar contacts as NES with Met909, leading to comparable potency as NES. In contrast, NES is not stabilized within the human androgen receptor (hAR)-LBD leading to negligible AR transactivation. Since progesterone acts in the brain by both PR-binding and indirectly via the metabolite allopregnanolone binding to GABA_A receptor (GABA_A_R), we investigated if NES is metabolized to 3α, 5α-tetrahydronestorone (3α, 5α-THNES) in the brain and if this metabolite could interact with GABA_A_R. In female mice, low concentrations of reduced NES metabolites were identified by Gas Chromatography-Mass Spectrometry in both plasma and brain. However, electrophysiological studies showed that 3α, 5α-THNES exhibited only limited activity to enhance GABAAR-evoked responses with WSS-1 cells and did not modulate synaptic GABA_A_Rs of mouse cortical neurons. Thus the inability of reduced metabolite of NES (3α, 5α-THNES) to activate GABA_A_R suggests that the neuroprotective and myelin regenerative effects of NES are mediated via PR binding and not via its interaction with the GABA_A_R

Time series visualization tools through a Virtual Observatory in geodesy

International audienceThis poster presents the context of the astronomical Virtual Observatory (VO), an ambitious international proposal to provide uniform, convenient access to disparate, geographically dispersed archives of astronomical data from software which runs on the computer on the astronomer's desktop. The VO could be of interest for the geodetic community: we present here some of our efforts in this direction that we have recently achieved, concerning the visualization of time series obtained from the analysis of space geodetic techniques. Some of these products are now natively built and archived following the data format recommended by IVOA, the VO-Table format. We present this format, which is based on the XML format, and we list the reasons why we chose to use it. Astronomers using that Virtual Observatory are now organized within an international association called the International Virtual Observatory Alliance (IVOA). As noted on the IVOA website (http://www.ivoa.net/), IVOA was formed in June 2002 with a mission to "facilitate the international coordination and collaboration necessary for the development and deployment of the tools, systems and organizational structures necessary to enable the international utilization of astronomical archives as an integrated and interoperating virtual observatory

Time series visualization tools through a Virtual Observatory in geodesy

International audienceThis poster presents the context of the astronomical Virtual Observatory (VO), an ambitious international proposal to provide uniform, convenient access to disparate, geographically dispersed archives of astronomical data from software which runs on the computer on the astronomer's desktop. The VO could be of interest for the geodetic community: we present here some of our efforts in this direction that we have recently achieved, concerning the visualization of time series obtained from the analysis of space geodetic techniques. Some of these products are now natively built and archived following the data format recommended by IVOA, the VO-Table format. We present this format, which is based on the XML format, and we list the reasons why we chose to use it. Astronomers using that Virtual Observatory are now organized within an international association called the International Virtual Observatory Alliance (IVOA). As noted on the IVOA website (http://www.ivoa.net/), IVOA was formed in June 2002 with a mission to "facilitate the international coordination and collaboration necessary for the development and deployment of the tools, systems and organizational structures necessary to enable the international utilization of astronomical archives as an integrated and interoperating virtual observatory

Why choosing the Virtual Observatory in Geodesy and Earth

International audienceThis poster presents the context of the astronomical Virtual Observatory (VO), an ambitious international proposal to provide uniform, convenient access to disparate, geographically dispersed archives of astronomical data from software which runs on the computer on the astronomer's desktop. The VO could be of interest for the geodetic community: we present here some of our efforts in this direction that we have recently achieved. Astronomers using that Virtual Observatory are now organized within an international association called the International Virtual Observatory Alliance (IVOA). As noted on the IVOA website (http://www.ivoa.net/), IVOA was formed in June 2002 with a mission to "facilitate the international coordination and collaboration necessary for the development and deployment of the tools, systems and organizational structures necessary to enable the international utilization of astronomical archives as an integrated and interoperating virtual observatory." The "Groupe de Recherche de Géodésie Spatiale (GRGS)" now routinely delivers geodetic products to most of the space geodetic services of the International Association of Geodesy (IAG): IERS, IGS, ILRS, IVS, and IDS. Some of these products are now natively built and archived following the data format recommended by IVOA, the VO-Table format. We present this format, which is based on the XML format, and we list the reasons why we chose to use it. We also enumerate the list of geodetic products actually published with this format, with the associated available Webservices, and we show how easy it is to compare time series obtained by various analysis centers. We finally give as well an example of such a comparison

Why choosing the Virtual Observatory in Geodesy and Earth

International audienceThis poster presents the context of the astronomical Virtual Observatory (VO), an ambitious international proposal to provide uniform, convenient access to disparate, geographically dispersed archives of astronomical data from software which runs on the computer on the astronomer's desktop. The VO could be of interest for the geodetic community: we present here some of our efforts in this direction that we have recently achieved. Astronomers using that Virtual Observatory are now organized within an international association called the International Virtual Observatory Alliance (IVOA). As noted on the IVOA website (http://www.ivoa.net/), IVOA was formed in June 2002 with a mission to "facilitate the international coordination and collaboration necessary for the development and deployment of the tools, systems and organizational structures necessary to enable the international utilization of astronomical archives as an integrated and interoperating virtual observatory." The "Groupe de Recherche de Géodésie Spatiale (GRGS)" now routinely delivers geodetic products to most of the space geodetic services of the International Association of Geodesy (IAG): IERS, IGS, ILRS, IVS, and IDS. Some of these products are now natively built and archived following the data format recommended by IVOA, the VO-Table format. We present this format, which is based on the XML format, and we list the reasons why we chose to use it. We also enumerate the list of geodetic products actually published with this format, with the associated available Webservices, and we show how easy it is to compare time series obtained by various analysis centers. We finally give as well an example of such a comparison