[-] wjs018@beehaw.org 24 points 1 year ago

The type of pill that was approved is the progestin-only "mini pill" which has a much safer clinical profile than the more common-in-the-US combination pill that has both progestin and estrogen. This type of pill is already available OTC in over 100 other countries. The US is just really behind the curve on just about anything to do with reproductive rights and care.

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submitted 1 year ago by wjs018@beehaw.org to c/science@beehaw.org

cross-posted from: https://mander.xyz/post/1133527

Paywall-free link: http://archive.today/oPjro

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submitted 1 year ago by wjs018@beehaw.org to c/microscopy@mander.xyz

Breakthrough here is the ability to image embryos comprised of living cells as opposed to post-mortem embryos.

original doi: https://doi.org/10.1016/j.cell.2023.06.003

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submitted 1 year ago by wjs018@beehaw.org to c/science@mander.xyz

This piece resonated with me as I also did not really envision myself working in industry when I started grad school; figuring that I would just stay in academia in one form or another. However, when I started to look outside academia (after seeing lab mates stuck in endless post-doc loops), I was surprised at the breadth of opportunities that were available.

Even though my degree was in physics, I was doing stuff relevant to several different industries. I interviewed for roles in data science, materials science, petrochemicals, food science, and pharma. Ultimately, I ended up in pharma and the very first program I worked on was an immunotherapy to target the type of cancer that caused the death of my grandfather. It wasn't some grand design on my part, just a coincidence that echoes some of what this author experienced.

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submitted 1 year ago by wjs018@beehaw.org to c/cooking@mander.xyz
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submitted 1 year ago by wjs018@beehaw.org to c/medicine@mander.xyz

The issue seems to be how the data was collected in the Phase 3 trial:

Clinical trials of most drugs and vaccines supporting FDA approval are mainly conducted in the U.S. and Europe, where clinical trial protocols are well recognized. The phase 3 TIDES trial used for Qdenga’s application was run in several less well-off, dengue-endemic regions in Latin America and Southeast Asia.

However, it should be noted that Takeda's drug, Qdenga, is already approved by the EMA in the EU and a couple other agencies. It is just the FDA that is holding things up in the US.

[-] wjs018@beehaw.org 6 points 1 year ago

Yeah, even comments here haven't seemed to read the article. As somebody that used to install BOINC on all my machines back in the day, the reason I stopped is that many of the projects I ran (SETI being one) aren't active any longer. Also, like the article mentioned, I just don't have a desktop anymore and I am not about to run something like this on a laptop that doesn't have things like user-serviceable or replaceable parts.

[-] wjs018@beehaw.org 7 points 1 year ago

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.

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submitted 1 year ago by wjs018@beehaw.org to c/space@beehaw.org

Continued fallout from the explosion of the Centaur upper stage on ULA's test stand as Vulcan's launch continues to slip.

In a statement, ULA described the work needed on the Centaur V upper stage as “minor reinforcement at the top of the forward dome,” or the uppermost section of the liquid hydrogen tank. The changes will add strength to the tank, which contains super-flammable fuel chilled to minus 423° Fahrenheit (minus 253° Celsius).

The pressure is on as the DOD is eagerly waiting for Vulcan.

The US Space Force is eager for the Vulcan rocket to enter service. The Pentagon selected ULA and SpaceX in 2020 to launch around 40 of the military’s most critical surveillance, communications, and navigation satellites from 2022 through 2028. ULA won the rights to launch about 60 percent of the missions, primarily using the new Vulcan rocket, with SpaceX taking the remaining 40 percent with its Falcon rocket family.

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submitted 1 year ago by wjs018@beehaw.org to c/space@beehaw.org

"The postponement is motivated by obligatory compliance with the prevention of forest fires... as well as the high temperatures" in southern Spain "to ensure the safety of the area where the launch is carried out".

First time I have seen this cited as a reason for a launch delay.

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submitted 1 year ago by wjs018@beehaw.org to c/biotech@mander.xyz

I haven't editorialized the title, but I don't like it since the desired protein structure was thought up by the grad student and the "digitally designed" piece just seems to be some MD modelling to confirm the desired outcome before synthesis.

That being said, I thought this was interesting since freeze/thaw (F/T) stress is ubiquitous in the life sciences and something that is especially important to the emerging field of cell therapy. Typically, excipients like sucrose, trehalose, or glycerol are used to preserve biological molecules during F/T, but they are not protective in every case. Developing alternative means to protect during F/T gives people like me that develop therapeutic formulations more options to turn to in the case of difficult molecules.

doi: https://dx.doi.org/10.1073/pnas.2220380120

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submitted 1 year ago by wjs018@beehaw.org to c/cooking@mander.xyz

This is about a recent study looking at the rheology of fondant. Essentially, fondant is created from a supersaturated solution of sucrose that is agitated (kneaded). This causes the fondant to experience a sequence of events:

  1. First, the agitation induces crystal nucleation and growth. In the early stages of crystal formation, the surrounding solution is depleted of sucrose, reducing the bulk viscosity.
  2. However, as the crystals grow in size, they are large enough to push against one another in hard sphere-like interactions. This causes a sharp increase in viscosity at this critical crystal size.
  3. As agitation continues, sucrose crystals fracture and the system reaches an equilibrium crystal size distribution, causing the viscosity to decrease from its peak. This is the final state of a smooth, pliable fondant.

There is a doi provided by the article, but as of my posting this, the doi hasn't been activated yet.

[-] wjs018@beehaw.org 4 points 1 year ago

The fine is from an unrelated, earlier incident in Alabama. From what I found on jalopnik:

Earlier this year, a worker was killed by being sucked into an airplane engine in Alabama on New Year’s Eve. The employee in that scenario was warned several times that the plane’s engines would be on, however. Still, OSHA hit the small airline Piedmont with a fine of $15,625 in the workers death.

This incident with Delta that happened in Texas is under investigation.

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submitted 1 year ago by wjs018@beehaw.org to c/medicine@mander.xyz

This is a summary of a Phase 1/2 trial of a cell therapy meant to stimulate insulin production in diabetes patients. The top line is that it met its clinical endpoints and several of the patients no longer require external insulin dosing at all and their blood sugar is well managed. Vertex also has a number of follow-up therapies in the pipeline meant to improve upon this therapy.

I personally don't have much experience in cell therapy, but the potential of a treatment like this is clear. We will see what the data looks like as this goes through the clinical trial pipeline and expands the patient population in Phase 3.

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submitted 1 year ago by wjs018@beehaw.org to c/science@mander.xyz

Not sure if TIL-type posts are allowed here, but thought that the story of the history of this event is interesting in a "history of science" type of way. If you want a narrative style of telling, you can check out this Smithsonian piece.

Story time! I watched Jurassic Park again recently and there is a bit in the movie where there is a discussion about competing theories for how the dinosaurs met their end. I didn't realize that back in the early 90's the impact theory was just one of a competing number of theories, so I did some reading.

Turns out that while doing readings to explore for gas/oil in the Caribbean, the Mexican state oil company, Pemex, had found evidence for the Chicxulub crater way back in the 1940's, but dismissed it as volcanic activity and moved on since volcanic regions are not great for oil extraction.

Fast forward to the late 70's and geophysicists are making additional measurements for Pemex and correctly ID the ring structure of these readings as a likely impact crater. The company is not really interested but consent to allow them to present their findings.

The cruel irony is that the conference at which the findings were presented occurred the same week that there was a special, separate conference with impact crater experts to discuss the impact theory of the end of the dinosaurs. So, there were no experts in attendance to learn about Chicxulub crater's existence from the Pemex scientists or recognize it's importance.

It took another 9 years, 1990, before the two worlds connected and further action was taken to ID Chicxulub as the impact crater that corresponded to the exact time period scientists were looking for.

Then, finally, it was 2010 before scientific consensus was (generally) reached that Chicxulub is the impact that ended the dinosaurs.

[-] wjs018@beehaw.org 21 points 1 year ago

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.org 4 points 1 year ago

I am glad I don't work in the clinical trial design space. It is already complicated enough to design a good clinical trial and this adds a whole other layer of complexity to it.

A sad component to this is that women are already underrepresented in clinical trials and this is likely to exacerbate the problem.

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submitted 1 year ago* (last edited 1 year ago) by wjs018@beehaw.org to c/medicine@mander.xyz

doi for the original Science piece: https://doi.org/10.1126/science.adh3104

[-] wjs018@beehaw.org 4 points 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.

[-] wjs018@beehaw.org 6 points 1 year ago

I work in this field and this is a great summary of mRNA and its therapeutic usage. The article does mention it, but mRNA is going to be widely used beyond vaccines as well.

As an example, at a previous company I worked at that had a robust pipeline and a portfolio of antibodies on the market, they were actively developing an mRNA-LNP version of all of their mAb programs. The idea is that if you develop an LNP platform that can reproducibly transfect say, the liver, then you can just turn the liver into a protein factory for anything you provide the mRNA sequence for. Having mAbs produced and excreted in the body solves one of the big challenges to convenient biologics dosing, bioavailability. Basically, a lot of antibodies, when injected under the skin, have trouble making it from the injection site to your bloodstream. This can be solved by administering via IV, but that has many downsides when it comes to patient convenience.

The reason vaccines are the first successful application of this technology is because they only require very small doses to be effective. Compare the amount of protein that is in a flu shot (60 micrograms in Fluzone at most) to a typical mAb (~150 mg up to 1 g at most), you can see how much less the vaccine requires. I fully expect that as the upstream and downstream processes for LNP manufacture improve and are able to scale, that we will see mRNA take over what is currently the realm of biologics.

[-] wjs018@beehaw.org 3 points 1 year ago

I added the link to the research paper above. Turns out the doi in the article is not correct.

[-] wjs018@beehaw.org 3 points 1 year ago

Great article summarizing the BBB. The brain is one of the highest priority targets for biologics therapeutics (viral & non-viral gene therapies, antibodies, peptides, etc.) and one of the most difficult to access via traditional routes of administration (IV, subcutaneous). I have worked on programs in the past that tried to access the brain via other administration methods (intrathecal, intraparenchymal), but both of these are quite invasive and lead to adverse events purely from the procedure. Engineering ways to cross the BBB would open up a huge number of potential therapeutic options for neurological disorders.

One of the other high priority targets that is difficult to access is the eye/retina. It has a similar set of biological barriers that prevent access to sensitive areas that are medically desired. If you want more reading on the eye, see this paper.

[-] wjs018@beehaw.org 51 points 2 years ago

Back in the olden days of reddit, mods didn't need to accept their position. So, it was a troll tactic to promote people to moderator of a controversial sub and then take a screenshot. I have no knowledge of spez's moderating history, but I imagine this is the most likely scenario.

[-] wjs018@beehaw.org 3 points 2 years ago

As an anime-only I have absolutely loved this series. I managed to go in completely blind and have been blown away. I am fully prepared to binge the manga as soon as this season is over.

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