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Although we observed clinical and histo-pathological differences caused by the compounds, we could still see some common biological processes that were affected by two or more compounds, which involve DNA damage response and cell death signaling, detoxification response, de-regulation of lipid metabolism and impaired immune response.
For example, if we searched PubChem bioassay data for the 962 ToxCast compounds, we could identify 193 PubChem assays that have at least five actives among these compounds (accessed in December of 2013).
For the majority of the tested compounds, we could find at least one active enzyme, even though the intensity of the activity varies a lot between the tested BVMOs.
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Independent of incubation time after removal of the compound, we could not detect any substantial inhibitory effect in this set-up (figure 6C), arguing against priming of the innate antiviral response by JMN3-003.
Corresponding to the postulated VEGFR-specific action of the HP-compounds, we could show a decrease in ERK1/2 activity after HP-treatment.
Since the alcohol form of HMF is not commercially available, nor the mass spectrum available for this compound, we could not conclude that a reductive conversion pathway was operating for this compound, though it seems quite likely.
With these four compounds we asked: Could HPLC-ICP-MS detect probe concentrations in the range observed in nuclear medicine?
Of these, available databases of known compounds capture in the tens of millions of structures [4], revealing a vast discrepancy between what has been synthesised/characterised and the compounds we think could be made.
Interestingly, the knock-down of XIAP and, partially, the simultaneous administration of the new SMAC-mimetic compounds we developed, could restore sensitivity of Me1007 cells to TRAIL-induced apoptosis.
Amounts of 28 of these compounds that we could reliably detect (see Table 5) significantly differed between populations, rearing substrates, and between the ventral abdomen and anogenital regions (Table 6).
After the analysis of the interaction data from the second and third compounds chosen, we could not find one H-bond occupancy over 50%.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com