This looks really promising. In 2018 this group found the antibodies to CD40 were potent antitumor agents, but there was platelet and hepatic toxicity that precluded systemic administration. But if you inject it directly into the tumor, the side-effects are much reduced, and there are no dose-limiting toxicities. Furthermore, you see an abscopal effect! Here's a nice diagram that shows all the things CD40 agonist antibodies can do. The upregulate MHC molecules and increased expression of OX40L, 4.1BBL, CD80 and CD86 which are costimulator antigens that can engage with CD28 on T-cells to enhance antitumor activation. Not shown in the diagram is that CD70 and also be upregulated, which engages with CD27 on T cells and NK cells to activate them as well. On macrophages, agonist CD40 antibodes turn them from the M2 phenotype to the more active antitumor M1 phenotype. And when these antibodies find to CD40 ligand on tumor cells, apoptosis is triggered, and the dead cells release antigens which the immune system can recognize and train against. This explains the amazing results seen in the phase I study.
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This study from Japan suggests that the
benefit from cocoa are not really from the flavonoids, but the astringent sensation that dark chocolate produces in the gut. This makes sense since the flavonoids are not well-absorbed, so how could they work in the brain, right? The response to astringency was enough to make mice react to the ingested flavonoids. I currently take
CocoaVia which has high bioavailability flavonoids due to their using (-)-epicatechin. I can't stand dark chocolate, and the effect on my gut isn't worth it.
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What jobs in tech are hot today? Machine learning engineering is really hot, it seems. Specifically engineers with specialization in robotics, developing proprietary models, and data center engineers.
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Interesting study which showed that when it came to language-specific tasks,
LLMs performed best in Polish, then Russian, French, Italian, Spanish, and then English. I guess English really is hard.
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Here's a nice article on the
timeline of SNAP changes. The bottom line is that people who are able to, best to get off SNAP. And while people are shocked by Los Angeles with 1 of 3 relying SNAP,
look at Salem, Eugene and Medford, where more than 1 of 5 rely on SNAP. In Portland, it's 1 of 6 that are using SNAP. Detroit is the worst, with 36% to 40% in SNAP participation. But I can't find a state like Oregon where nearly all of the big cities have >20% SNAP participation.
And who are the ones getting SNAP benefits?
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Washington state put out an infographic on the chronically homeless. Maybe just to show that Oregon is worse.
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