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To examine whether our DNA vaccine had sufficient potency to be scaled from mouse to human, we examined the delivery of our DNA vaccine using the Inovio Elgen100 device for the first time in the clinic.
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Some human-specific parameter values are directly taken from mouse values, and they may be properly scaled from mouse to human or be determined by performing appropriate experiments.
Cell membrane transport parameters were scaled up from mice to humans by assuming that the contact surface between interstitial and intracellular mediums was proportional to the cell volume such that: where p stands for,,, or, and for the normal brain or tumor intracellular volume.
Fly genes were scaled to 1.2 kb and values were extracted from published data sets, mouse genes were scaled to 30 kb.
Mouse time-activity curves were scaled to human using the organ-weight scaling method and published kidney compartment sizes [18].
The concentration and amount of food was simply scaled up from a mouse weighing less than an ounce, to a human weighing 150 lbs (2,400 ounces), without regard to major metabolic, immune system or digestive tract differences.
Mouse polyclonal antibodies were purified from mouse sera using Nab Protein A/G Spin Kit (Thermo Scientific, Rockford, IL) that allows small-scale affinity purification of antibodies from serum.
Rab3a was cloned from mouse brain cDNA.
Endothelial cells were isolated from mouse aorta.
DNA was extracted from mouse tail tips.
Transport parameters from blood to interstitial fluid were either directly scaled up from the mouse study—referred to as the naive estimation or estimated using TMZ normal brain concentrations measured by intracerebral microdialysis in the same seven patients from whom plasma measurements were available.
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