Thank you.
So Pat has set the stage for this.
Years ago, a friend of mine, Dave Dignam, Dave was actually in Mississippi when I first
went there 37 years ago and then he left.
But we see one another at meetings.
And in the last more than 10 years, he had been working on this pegalation problem.
And he had clinical collaborators who were trying to develop a potential clinical mechanism
for treating sepsis.
There's a lot of dehydration events that go on in sepsis.
So it was sort of a straight and linear process.
And there are numerous patents that they've produced.
So the conversation was basically make a bunch of pegalated serum albumin and then characterize
these linear.
And we did one branched 40K.
That one historically is known as Pegasus, if you're familiar with the field.
And then measure AUC sedimentation velocity to get the appropriate values, Ks, 2BM1, Stokes
radius shape.
Measure DLS to get the interaction parameter Kd and Rs from Stokes-Einstein-Sutherland
equation.
Measure AUC sedimentation equilibrium to validate the virial coefficient by another method.
And then use what we're calling the Rowe equation.
Does Arthur mind that we're turning it into his equation?
I don't know.
To estimate the shape, the hydration.
So I'm doing something intrinsically different here.
We're measuring Ks.
We're inferring F over F0 from the S0 intercept.
And then we're going to measure the S value, the swollen volume.
And then my goal actually was, because there isn't a lot of literature on it, but there's
this paper from years ago that Steve published showing that Ks plus Kd equals 2BM1.
You can show it simply in a simple derivation.
The question is, there's not a lot of experimental evidence for it.
There's about three papers actually that show it.
And I thought it would be nice to add that to the list.
About two years ago, we had been done with this project.
And there were lots of problems with the project.
We couldn't understand a lot of the data.
A lot of things were non-linear.
There was a lot of curvature.
Things sort of didn't add up.
And so in Lethbridge, Pat and I were talking about water.
Pat kept asking me about water.
And we ended up publishing a paper a year ago on measuring entrained water using HULRED.
But at the same time, I knew we needed to simulate PEG.
So Pat said, yay, I can do that once we publish the other paper.
And then he started working on the PEG.
So for more than two years now, we've been doing these two projects.
And so we're now done.
We think we're done, or we're kind of dumb.
So that's where we are.
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Aufnahmedatum
2024-09-02
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