This is really cool! Any tips for finding poems hidden in a large block of text?
It reminds me of the poem composed from one of Trump's tweets: "O, the Pelican. so smoothly doth he crest. a wind god!" There are lots of other examples on
r/othepelican.
(Creator here) It's something I'd like to spend more time on! I didn't have a good time with LLM prompting but I think maybe something deterministic similar to Nutrimatic https://nutrimatic.org/2024/ might produce better results.
Likewise–I pop it on the charger in the shower and occasionally at work if I'm at my desk. The alarms, timers, and reminders access (via Siri) more than makes up for the inconvenience of frequent charging. Notifications for messages and e-mails is just a bonus that sometimes ends up being a double-edged sword. The only downsides for me come on long bike rides, and that it is ugly (and getting too big, coming from a Casio F91-W).
I’ve owned both and the truth is Garmin makes the best fitness tracker that can be a smartwatch and Apple makes the best smartwatch that can be a fitness tracker.
This comment hits the nail on the head. Another big consideration with the technology in this paper that hasn't been mentioned in this thread is that it opens up a huge range of possibilities for targeting "undruggable" protein targets. Most drugs are small molecules that bind to sites an (relatively much larger) proteins, thereby getting in the way of their function. Unfortunately the vast majority of proteins do not have a site that can be bound by a molecule in a way that 1) has high affinity, 2) has high specificity (doesn't bind to other proteins) and 3) actually abolishes the protein's activity.
With "induced proximity" approaches like the one in this study, all you need is a molecule that binds the target protein somewhere. This idea has been validated extensively in the field of "targeted protein degradation", where a target protein and an E3 ubiquitin ligase, a protein that recruits the cell's native proteolysis machinery, are recruited to each other. The target protein doesn't have to be inactivated by the therapeutic molecule because the proteolysis machinery destroys it, so requirement #3 from above is effectively removed.
The molecule in this study does something similar to targeted protein degradation, but this time using a protein that effects gene expression instead of one that recruits proteolysis machinery. The article focuses on the fact that cancers are addicted to BCL6. This is an important innovation in the study and an active area of research (another example at [1]), but leaves out the fact that these induced proximity platforms are much more generalizable than traditional small molecules because it's the proteins that they recruit that do all the work rather than the molecules themselves. This study goes a long way to validate this principle, pioneered by targeted protein degradation and PROTACs, and shows that it can be applied broadly.
There are two semi-connected concepts at play here. Polarization in this context refers to the ratio of neutralizing (i.e. "up" vs "down") spins in a given system. For most nuclei in organic systems like protons, carbons, and nitrogens, this ratio is naturally very small, which is the reason that magnetic resonance approaches like MRI usually have poor signal-to-noise. Hyperpolarization techniques usually involve the transfer of polarization from a source of high ratio, like a free electron, to a relevant target (in the original poster's example, 13C in pyruvate). The polarization in this case is hyperpolarized 13C, which has an "up"-to-"down" spin ratio that is much higher than regular 13C, which makes the signal-to-noise that you get from the pyruvate much higher than it would be otherwise. Tumors love pyruvate so this approach means that tumors will light up like a beacon in your MRI.
The physical rotation/tumbling of molecules in an MRI is also very important, because the strong magnetic field is the thing inducing the "up"-vs-"down" split in the first place, and if the molecular motion is happening at a certain frequency with respect to the external magnetic field there are other interactions that can come into play which can affect the coherence of the nuclear spins (i.e. they can fall out of sync). Thankfully, the rotation of a small molecule like pyruvate is very fast (might higher then the "spin" frequency-a.k.a the Larmor frequenct of 13C at the magnetic field strengths involved in MRI) so the physical tumbling of pyruvate doesn't really come into play when trying to measure its signal. It can be another story for molecules that don't tumble quickly, like the ones that make up tissues, fat, etc.
Great explanation. Indeed, the "rotation/tumbling" is nothing to worry about. One of our biggest challenges is relaxation. The moment we polarize, the clock ticks. Usually, the time scope is around 15-90s. I'm in the field of para-hydrogen and built automated systems which carry out the chemical reactions, polarization transfers and sample cleaning. Many hyperpolarization experiments with para-hydrogen prefer nasty solvents as chloroform or methanol. It is a technical challenge to replace them by water within seconds. One of my favorite topics is Xenon hyperpolarization. It's very elegant, no cleaning required, no wet chemistry, and provides amazing lung scans.
I solved this with a ~$200 driver board from AliExpress. I love the result because it's thinner than any other monitor that I own and I can swap between my MacBook Pro and my desktop machine (running either Windows or Linux).
Obviously this requires a little bit of tinkering and the end result isn't nicely packaged like a factory Apple product would be, but it only took about half an hour to put together and I haven't had any issues with the driver board yet. And it was way cheaper than a "Retina" display from Apple or LG.
I didn't bother to mess around with mounting, I just used command strips to attach the driver board to the back of the monitor and mounted the monitor on one of these clamp-type stands:
I solved it by not updating the OS or apps. I stopped updating at Mountain Lion. My older iMac is my scanning and photo editing Mac. A flatbed scanner is permanently attached and Photos from Mountain Lion is still useable. In fact the retouch tool is actually faster (Photos experienced a serious performance regression for the retouch tool soon after Mountain Lion).
My guess is that this area is much harder to break into–enzymes facilitate challenging chemical transformations by stabilizing high-energy transition states in chemical reactions. These states are usually highly transient and therefore much harder to capture using the structural biology techniques that generate the structural data that AlphaFold and similar methods are trained on. Even though there are many structures of enzymes in the absence of their substrate, I would imagine that the small number of structures for states that represent actual catalytic intermediates would make it difficult for a model to internalize the features that distinguish a good enzyme/catalyst from a bad one.
Another consideration is that most protein structure prediction methods only generate the backbone, and the sidechains are modeled in afterwards. Enzyme efficiency requires sub-A level structural precision in the sidechains that are actually doing the chemistry involved in catalysis, so it could also be the case that the current backbone-centric methods aren't good enough to predict these fine-tuned interactions.
Looking forward to walking to the corner store in my Arc'teryx x Kith exoskeleton. Jokes aside, this is really cool. I hope I won't need one for a while, and look forward to the engineering improvements when I do need one.
I wonder how this will compare to Arc's "Browse for me" feature–at least for a single search (I don't thing the chat-based interface will be much of a value add here beyond just running a second "Browse for me"/SearchGPT). I really like the "Browse for me" feature, but only in specific cases, and I don't think I'd ever use it if it was a standalone app and not a built-in feature of Arc that also lets me run a quick google search.
I've done this and it's amazing-it's the only monitor that I can use for my workstation (Linux/Windows) and my laptop (macOS) because even the (relatively) cheap LG UltraFine monitors don't work with the Nvidia GPU on my workstation.
This would be cool if it weren’t so heavy-handed—a similar application to add tags to files or some metadata that could be indexed by Alfred or Rofi would be cool.
It reminds me of the poem composed from one of Trump's tweets: "O, the Pelican. so smoothly doth he crest. a wind god!" There are lots of other examples on r/othepelican.