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Cake day: June 13th, 2023

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  • This is interesting and I wish that he went into some more detail on how they spray dry without destroying protein activity. I actually have some first-hand experience trying to develop a spray drying method for antibody solutions for immunotherapy products. Ultimately, I left that company, but the real big problem was that most antibodies can’t survive the temperature needed for spray drying. For this reason, usually freeze drying is used instead (there are even techniques for spray freeze drying). They claim that the process inactivates viral capsids, but preserves antibody activity and having worked with both in the past, that seems like a bold claim.


  • I don’t think they have given a complete list of what will be included. For the first two episodes it is as follows based on a quick scan of the manga. I don’t really have the time to go through the whole first season, but as you can see from episode 1, they are likely to jump around a bit.

    Episode Manga Chapters
    Episode 1 6, 40
    Episode 2 47-50

    Edit: I did go back through some of the first season, but I ran out of time, so here is the first half the season (roughly):

    Episode Manga Chapters
    Episode 1 1-3
    Episode 2 4, 7, 9
    Episode 3 10-13
    Episode 4 16-20
    Episode 5 21-24
    Episode 6 26-27, 29-30
    Episode 7 34-37









  • I think that @saccharomyces@mander.xyz provided a great response for the specific case of flow in a pipe.

    I just want to add that if you look beyond the restrictions of flow in a pipe, there are many other types of behavior that non-Newtonian fluids exhibit. We measure this in the lab on instruments called rheometers. Basically, we put some liquid in the instrument and then deform it and measure the resistance to that deformation. One of the most common ways to apply that deformation is to do so back and forth in an oscillating manner. Depending on the frequency at which you apply this strain, the solid/liquid-like behavior can change. If you have some background in physics or want to get a decent understanding, I found this paper that, on skimming it, seems to be pretty consistent with the way I was taught this stuff in grad school.

    One graph I want to point out is Figure 13 which shows what would be a “typical” viscoelastic polymer solution. An easy way to understand this graph is that as we go from left to right, we are applying strain back and forth quicker and quicker, essentially shaking it faster. When the G’ value is higher than the G" value, then the material is behaving more like a solid and conversely, when G" > G’, then it is behaving more like a liquid. You can see that the material goes through different phases of behavior as the strain frequency changes. Just for you I went and dug up an old graph from my thesis to show a real-life example of this happening too.

    My favorite demonstration of this is to put Oobleck (or something similar) onto a speaker and then change the frequency and see what happens.








  • So, it has been a while since I read the manhwa (I haven’t read the original webnovel), but I am overall pleased with how the adaptation has gone so far. You could definitely tell that there were very limited budgets. There are so many instances of slideshow animations or just still images, but they seemed to invest heavily in making beautiful stills and backgrounds.

    My major complaint about the show is that, in general, it has gone very slowly. I expected them to be further along in the story after 12 episodes, but the pacing has been plodding at best. If my memory serves, I think they adapted 3 of the 7 volumes of the manhwa. I understand that a lot of shows tend to go too quickly, but this show just seems to drag out every conversation like it is padding for time (maybe to help stretch the animation budget too).

    Overall happy with the show so far and hope that if it gets a second season it gets a bit more resources thrown its way.



  • That is true. Vertex claims that some of the follow-up therapies to this do not require immunosuppressants, so time will tell.

    From a strategic perspective, I wonder if they will proceed with Phase 3 or not. I have worked on several programs in the past where we pushed through to Phase 2 to get a proof of concept in humans before scrapping the program because we have a better version of the molecule (using the same mechanism of action) getting ready right behind it. This therapy from Vertex may have proven the concept to allow a better version to come next.




  • That’s fair. I couldn’t find much info on their website, so I assumed this was another make insulin cheap using “biohacking” deal. I don’t have any experience with small molecule synthesis or dry powder manufacturing, so I can’t really speak to how feasible this may be. However, having seen first-hand all the ways simple manufacturing steps can go wrong, the risk of consuming a medication that hasn’t been through rigorous QA/QC makes me very wary.


  • Apologies for the long post. I don’t mean this as an attack on OP, just trying to illustrate why actually doing this is a bad idea.

    I have seen efforts like this in the past, especially centered around efforts to manufacture insulin cheaply. While I get that medicine cost and availability is broken at a fundamental level in the US, the solution is a political one rather than to run a wildcat bioreactor. There is simply no way to safely manufacture biologics using a 3d printed bioreactor. Let’s look at the manufacturing process to get an idea of why.

    Staring with the bioreactor, you would need some way to sterilize it before use (not just sanitize, there’s a difference). There are plastic bioreactors that are used in industry, but they are large, single-use bags that are sterilized using gamma or x-ray radiation. Most industry bioreactors are made of stainless steel to withstand the harsh treatment required to re-sterilize them (steam or hydrogen peroxide).

    Moving down the chain from the bioreactor, you need some way to remove your product from the harvested liquid. This is usually done through lysing the cells you have grown and then running this lysate through a series of chromatography columns of varying types (affinity, ionic, etc.) to systematically remove all the junk left over from your cellular media and the cells you have lysed. Even if you could (unsafely) grow your cells and drug in a 3d printed bioreactor, you don’t have these kinds of things at home and can’t just get them from Amazon.

    However, let’s say that you could get past the purification step, what’s next? You find yourself with a large volume of very dilute medicine suspended in a chromatography buffer. The next step is what is called UF/DF, or ultra-filtration/dia-filtration. This step, paradoxically done DF first, uses filter membranes and large amounts of buffer and some pressure to first swap out the buffer that your medicine is in to the target formulation that you want to inject and then concentrate it down to a manageable volume. If you are working at small scale, then you can probably replace this step with just one filter and a centrifuge. Remember that while you are doing all this, everything that comes into contact with your drug needs to be sterile (even the air).

    I think I have made my point, but for actual drugs there are more steps beyond this. Post-UF/DF is what is referred to as drug substance (DS) in the industry. You still need to go through a sterile fill-finish process to get drug product (DP) that is what is actually given to a patient. If you really want, I can go on another long tirade here since this is the step my job focuses on.

    I have worked on these manufacturing processes and seen them fail a lot for very hard to catch problems. Without all the in-process controls and testing we do, there would have been serious risks of giving bad DP to patients. If you have read this far, then I hope I’ve convinced you not to give this kind of thing a try.

    The real problem this is trying to solve is a political one. We should be advocating for better access to medications and reforming how costs are dealt with. It doesn’t matter what your political persuasion is, I think everyone agrees healthcare in the US is broken and it’s time something is done about it.





  • wjs018@beehaw.orgtoScience@beehaw.orgmRNA Vaccine Science
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    1 year ago

    It hopefully should. One of the main reasons biologics are so expensive isn’t just corporate greed (though it is that too), but because the manufacturing process is very intense. Running bioreactors at commercial scale to make your product, using a train of chromatography steps to purify it, and then filtering it to be concentrated and sterile before fill/finish in a pre-filled syringe or vial followed sometimes by lyophilization is an insanely complicated process that is very costly. mRNA processes simplify this a lot in that the mRNA don’t need to be manufactured using bioreactors that are filled with dirty cellular flotsam and jetsam that need removed. So, the production and purification parts are much much simpler. It still isn’t likely to be cheap, as GMP manufacturing is still complex and the fill/finish part of the operations are largely unchanged, but hopefully cheaper.