Discovery and SAR of a novel series of non-MPEP site mGlu(5) PAMs based on an aryl glycine sulfonammide scaffold

Herein we report the discovery and SAR of a novel series of non-MPEP site metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) based on an aryl glycine sulfonamide scaffold. This series represents a rare non-MPEP site mGlu(5) PAM chemotype.

P3 SAR exploration of biphenyl carbamate based Legumain inhibitors

This Letter describes the further development and SAR exploration of a novel series of Legumain inhibitors. Based upon a previously identified Legumain inhibitor from our group, we explored the SAR of the carbamate phenyl ring system to probe the P3 pocket of the enzyme. This led to the identification of a sub-nanomolar inhibitor of Legumain.



Graphical abstract

Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors

This letter describes the design, development and SAR exploration of a novel series of small legumain inhibitors. The SAR of a new small molecule legumain inhibitor chemotype was explored and found to have improved physiochemical properties compared to previously developed inhibitors within our group. However, further development of this series was found to be limited as the SAR was observed to be relatively flat.

SAR determination and influence of the human head in the radiation of a mobile antenna for two different frequencies

The big proliferation of mobile communication systems has caused an increased concern about the interaction between the human body and the antennas of mobile handsets. In order to study the problem, a multiband antenna was designed, fabricated and measured to operate over two frequency sub bands 900 and 1800 MHz. After that, we simulated the same antenna, but now, in the presence of a human head model to analyze the head's influence. First, the influence of the human head on the radiation efficiency of the antenna has been investigated as a function of the distance between the head and the antenna and with the inclination of the antenna. Furthermore, the relative amount of the electromagnetic power absorbed in the head has been obtained.

Development of hypogene and supergene alteration and copper mineralization patterns, Sar Cheshmeh porphyry copper deposits, Iran /

The formation of the Sar Cheshmeh porphyry Cu-Mo deposit is related to the culmination of calc-alkaline igneous activity in the Kerman region. The deposit comprises a suite of Late Cenozoic intrusive sub-volcanic and extrusive rocks emplaced into a folded series of Eocene andesitic lavas and pyroclastic sediments. The earliest stage of magmatism was emplacement of a large granodiorite stock about 29 m.y.b.p. This was followed by intrusion of two separate porphyritic bodies at 15 (Sar Cheshrneh porphyry) and 12 m.y.b.p. (Late porphyry) and a series of sub-volcanic dikes between 12 and 9 m.y.b.p. Magmatic activity terminated with multi-phase extrusion of a Pelean dacitic dome complex between 10 and 2.8 m.y.b.p. The country rocks and the earlier porphyritic intrusions are pervasively altered to biotite-rich potassium silicate (metasomatic and hydrothermal) sericite-clay, phyllic and chlorite-clay, argillic assemblages. These grade outwards to an extensive propylitic zone. Within the ore body, the later intra-. and post-mineral dikes only reach the propylitic grade. At least three different sets of quartz veins are present, including a sericite-chlorite-quartz set which locally retrogrades pervasive secondary biotite to sericite. In the hypogene zone, metasomatic and hydrothermal alteration is related to all stages of magmatism but copper mineralization and veining are restricted to a period of 15 to 9 m.y.b.p.related to the early intrusive phases. The copper mineralization and silicate alteration do not fit a simple annular ring model but have been greatly modified by, 1. The existence of an ititial, outer ring, of metasomatic alteration overprinted by an inner.ring of hydrothermal alteration and, 2. later extensive dilating effects of intra- and post-mineral dikes. The hydrothermal clay mineral assemblage in the hypogene zone is illite-chlorite-kaolinite-smectite (beidellite). Preliminary studies indicate that the amount of each of these clays varies vertically and that hydrothermal zonation of clay minerals is possible. However, these minerals alter to illite-kaolinite assemblages in the supergene sulfide zone and to more kaolinite-rich assemblages in the supergene leached zone. Hydrothermal biotite breaks down readily in the supergene zone and is not well preserved in surface outcrops. The distribution of copper minerals in the supergene sulfide enrichment zone is only partly related to rock type being more dependent on topography and the availability of fractures.

Educación y compromiso : el IES de Sar responde ante la catástrofe del Prestige y la guerra contra Irak.

El artículo forma parte de un monográfico de la revista dedicado a educación ambiental en tiempos de catástrofes

Using airborne laser altimetry to improve river flood extents delineated from SAR data

Flood extent maps derived from SAR images are a useful source of data for validating hydraulic models of river flood flow. The accuracy of such maps is reduced by a number of factors, including changes in returns from the water surface caused by different meteorological conditions and the presence of emergent vegetation. The paper describes how improved accuracy can be achieved by modifying an existing flood extent delineation algorithm to use airborne laser altimetry (LiDAR) as well as SAR data. The LiDAR data provide an additional constraint that waterline (land-water boundary) heights should vary smoothly along the flooded reach. The method was tested on a SAR image of a flood for which contemporaneous aerial photography existed, together with LiDAR data of the un-flooded reach. Waterline heights of the SAR flood extent conditioned on both SAR and LiDAR data matched the corresponding heights from the aerial photo waterline significantly more closely than those from the SAR flood extent conditioned only on SAR data.

Global scale water stages from SAR imagery (GlosSARi) to support global flood forecasting

Despite the success of studies attempting to integrate remotely sensed data and flood modelling and the need to provide near-real time data routinely on a global scale as well as setting up online data archives, there is to date a lack of spatially and temporally distributed hydraulic parameters to support ongoing efforts in modelling. Therefore, the objective of this project is to provide a global evaluation and benchmark data set of floodplain water stages with uncertainties and assimilation in a large scale flood model using space-borne radar imagery. An algorithm is developed for automated retrieval of water stages with uncertainties from a sequence of radar imagery and data are assimilated in a flood model using the Tewkesbury 2007 flood event as a feasibility study. The retrieval method that we employ is based on possibility theory which is an extension of fuzzy sets and that encompasses probability theory. In our case we first attempt to identify main sources of uncertainty in the retrieval of water stages from radar imagery for which we define physically meaningful ranges of parameter values. Possibilities of values are then computed for each parameter using a triangular ‘membership’ function. This procedure allows the computation of possible values of water stages at maximum flood extents along a river at many different locations. At a later stage in the project these data are then used in assimilation, calibration or validation of a flood model. The application is subsequently extended to a global scale using wide swath radar imagery and a simple global flood forecasting model thereby providing improved river discharge estimates to update the latter.