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Particulate methane monooxygenase (pMMO) produced in methanotrophs (e.g., Methylosinus trichosporium OB3b, Methylococcus capsulatus) degrade a wide variety of toxic organic compounds (Yoon 2010; Pandey et al. 2014), especially chlorinated ethenes (Tsien et al. 1989; Yoon 2010) via a cascade of enzymatic reactions involving the production of formaldehydes that later produce terminal compound CO2.
Aiming to address if a parallel increase of redox state took place in the periphery, we evaluated malondialdehyde (MDA), a terminal compound derived from lipid peroxidation and from eicosanoid biosynthesis, widely used to monitor oxidative stress [25].
Mean AC163794 concentration in plasma was 15.4 ± 2.9 ng/ml and terminal compound concentrations correlated with HbA1c values (r = 0.6).
In this 2-week study, terminal compound levels were also comparable: 4.6±3.2 μ M for torcetrapib and 9.4±3.1 μ M for anacetrapib.
In the study shown in Figure 1, the two compounds achieved comparable systemic exposure: in the wild-type mice, terminal compound levels were 23±4 μ M of torcetrapib and 25±3 μ M of anacetrapib.
The lack of a dose response in Aβx-40 species in PDAPP & FVB mice compared with Aβ1-x species in PDAPP mice can not be explained by differences in terminal compound levels in the target organ at the two doses tested, nor by assay differences.
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In the multi-terminal compound network formulations, all nodes are missing identical information about the channels in the network whereas in our formulation, the 1-local view results in asymmetric and mismatched information about channels at different nodes.
UDP-GlcNAz (1, Figure 1) was used as a sugar donor and the TAMRA-conjugated terminal alkyne compound (TAMRA-Alkyne, 2, Figure 1) or biotinylated triarylphosphine compound (Biotin-Phosphine, 3, Figure 1) were used as reagents to selectively react with the azido-functionality.
Stored in the chemical bond holding the terminal phosphate compound onto the ATP molecule is the energy derived from the breakdown of sugars.
Terminal plasma compound levels at the highest dose tested were 12.3 μM, or a more than six-fold multiple over the cellular IC50 for inhibition of Notch signaling.
Terminal plasma compound levels at the highest dose tested were 12.3 μM, a 17-fold multiple over the cellular IC50 for inhibition of Notch signaling.
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