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The mouse plasma protein binding for 7a and 7d was determined as 99.48% and >99.9%, respectively.
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For determining 15N incorporation in plasma, 15N and 14N mouse plasma proteins were mixed at a 1∶1 ratio (v/v) and processed as described for the brain samples.
By comparing the upregulated mouse plasma proteins with the list of proteins enriched in the surface or secreted cellular compartments from human ovarian cancer cells (Table S2), 55% (58/106) of upregulated proteins in mouse plasma were found to be released from ovarian cancer cells through secretion or shedding or enriched in the ovarian cancer cell surface compartment.
These results (Table 3) show DRDE-07 binding to mouse plasma proteins (21.82%–24.54%).
Two mouse plasma proteins involved in cell defence, namely murinoglobulin 2 and kininogen 2 were exclusively expressed in the liver.
The compound was highly plasma protein bound to human plasma proteins (>99%), though it was somewhat less tightly bound to mouse plasma proteins (∼84%).
Among these candidate proteins, one protein molecule, senescence marker protein 30 (SMP30), caught our interest because it only appeared on the 2-D gels of ALF mouse plasma proteins.
The compound is not tightly bound to mouse plasma proteins (fraction unbound is 0.69) and is well tolerated when administered at 150 mg kg−1 via the oral route.
In addition, the presence of mouse plasma DING protein is consistent with the recent purification of a human DING representative HPBP in the blood as published by Morales et al. [16].
However the finding of elevated levels in mouse plasma of proteins previously associated more broadly with ovarian cancer, led us to investigate the merits of integrating mouse plasma proteomic findings from this model with proteomic findings from ovarian cancer cells.
In this study, five proteins that exhibited significant differences in plasmas from subjects with ovarian cancer relative to controls were comprised predominantly of secreted proteins at the intersection of upregulated proteins in mouse plasma and secreted proteins in proteomic data from ovarian cancer cell populations.
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