Cross-Phase Determination of Ultralow Frequency Wave Harmonic Frequencies and Their Associated Plasma Mass Density Distributions

Latitudinally spaced ground‐based magnetometers can be used to estimate the eigenfrequencies of magnetic field lines using the cross‐phase technique. These eigenfrequencies can be used with a magnetic field model and an assumed plasma mass density distribution to determine the plasma mass density in the magnetosphere. Automating this process can be difficult, and so far, it has not been possible to distinguish between the different harmonics. Misidentification of the harmonic mode will lead to incorrect estimations of the plasma mass density. We have developed an algorithm capable of identifying multiple harmonics in cross‐phase spectrograms, using International Monitor for Auroral Geomagnetic Effects magnetometers. Knowledge of multiple harmonics allows the distribution of plasma mass density to be estimated instead of assumed. A statistical study was performed that showed clear common bands of eigenfrequencies, interpreted as different harmonics. These eigenfrequencies were lowest in the early afternoon and at higher latitudes. There was also a greater occurrence of measurements in the dayside. We then modeled the plasma mass density distribution with a power law characterized by the exponent p and compared the model eigenfrequencies to the data. This suggested that the even modes did not form during the interval of this study. Examination of the harmonic spacing and the high occurrence of the third harmonic supported this suggestion. We attribute the absence of the even modes to the driving mechanisms. Finally, we show that an equatorial bulge in plasma mass density was not present in our study

Species Used for Drug Testing Reveal Different Inhibition Susceptibility for 17beta-Hydroxysteroid Dehydrogenase Type 1

Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD 1) for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17β-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17β-HSD types 1, 2, 4, 5 and 7 but also against 17β-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17β-HSDs analyzed were observed. Especially, the rodent 17β-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17β-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution