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Short-term variability of solar wind number density, speed and dynamic pressure as a function of the interplanetary magnetic field components: A survey over two solar cycles
The variability of hourly values of solar wind number density, number density variation, speed, speed variation and dynamic pressure with IMF Bz and magnitude |B| has been examined for the period 1965–1986. We wish to draw attention to a strong correlation in number density and number density fluctuation with IMF Bz characterised by a symmetric increasing trend in these quantities away from Bz = 0 nT. The fluctuation level in solar wind speed is found to be relatively independent of Bz. We infer that number density and number density variability dominate in controlling solar wind dynamic pressure and dynamic pressure variability. It is also found that dynamic pressure is correlated with each component of IMF and that there is evidence of morphological differences between the variation with each component. Finally, we examine the variation of number density, speed, dynamic pressure and fluctuation level in number density and speed with IMF magnitude |B|. Again we find that number density variation dominates over solar wind speed in controlling dynamic pressure
Inconsistency Management in Heterogeneous Models - An Approach for the Identification of Model Dependencies and Potential Inconsistencies
Interactions of porphyrinyl-nucleosides with DNA using the example of porphyrinyl-thymidine
Functional genomic approaches for the study of fetal/placental development in swine with special emphasis on imprinted genes
Monoclonal antibodies that recognize the alkylation signature of antimalarial ozonides OZ277 (Arterolane) and OZ439 ( Artefenomel)
The
singular structure of artemisinin, with its embedded 1,2,4-trioxane
heterocycle, has inspired the discovery of numerous semisynthetic
artemisinin and structurally diverse synthetic peroxide antimalarials,
including ozonides OZ277 (arterolane) and OZ439 (artefenomel). Despite
the critical importance of artemisinin combination therapies (ACTs),
the precise mode of action of peroxidic antimalarials is not fully
understood. However, it has long been proposed that the peroxide bond
in artemisinin and other antimalarial peroxides undergoes reductive
activation by ferrous heme released during hemoglobin digestion to
produce carbon-centered radicals that alkylate heme and parasite proteins.
To probe the mode of action of OZ277 and OZ439, this paper now describes
initial studies with monoclonal antibodies that recognize the alkylation
signature (sum of heme and protein alkylation) of these synthetic
peroxides. Immunofluorescence experiments conducted with ozonide-treated
parasite cultures showed that ozonide alkylation is restricted to
the parasite, as no signal was found in the erythrocyte or its membrane.
In Western blot experiments with ozonide-treated Plasmodium
falciparum malaria parasites, distinct protein bands
were observed. Significantly, no protein bands were detected in parallel
Western blot experiments performed with lysates from ozonide-treated Babesia divergens, parasites that also proliferate
inside erythrocytes but, in contrast to <i>P. falciparum</i>, do not catabolize hemoglobin. However, subsequent immunoprecipitation
experiments with these antibodies failed to identify the <i>P.
falciparum</i> proteins alkylated by OZ277 and OZ439. To the
best of the authors’ knowledge, this shows for the first time
that antimalarial ozonides, such as the artemisinins, alkylate proteins
in <i>P. falciparum</i>
