Today I made this "Hierarchy of Immunotherapy" to organize my notes/thoughts. Any feedback? Corrections/improvements?

people aren’t celebrating this pancreatic cancer breakthrough enough. it should be international news

Hamming's talk is so important that I reproduced it on my site. It's one of the only things on my site written by someone else. paulgraham.com/hamming.html

Fox's Aishah Hasnie: Karoline Leavitt's husband leaned over and told me right as the WH Correspondents Dinner was starting, "You need to be very safe." "He was very serious when that said that to me, and he kinda looked around the room and said, 'There are some–'" *Call drops*

This tweet two hours before the event.

“Traders” made millions-billions? No, President and his children made these trades.

I have three monitors on my desk. The left one shows the order book. The middle one shows Truth Social. The right one shows the investigation queue. On April 21st, the left screen moved first. I am a Senior Surveillance Analyst at a commodities exchange. I have held this position for nineteen years. My job is to monitor trading activity for suspicious patterns and generate compliance reports. I am employee of the quarter. I have a mug. At 19:54 GMT on April 21st, someone placed 4,260 sell orders on Brent crude futures. They did this during post-settlement. The window after the market closes when daily volume is typically in the dozens. Sometimes single digits. Sometimes I watch the screen and nothing happens for forty minutes and I think about whether my daughter is happy. On April 21st, someone placed $430 million in directional bets in 120 seconds during that window. One hundred and twenty seconds. I timed it on my watch because the system clock rounds to the nearest minute and I have found, in nineteen years, that precision matters to no one but me. At 20:10 GMT, the President posted on Truth Social that he was extending the Iran ceasefire. Brent dropped from $100.91 to $96.83. I flagged the trade. I flag a lot of trades. I want to tell you what happens to my flags. My flags go into a system called TRACE. Trade Review and Compliance Evaluation. I did not name it. The system generates a report. The report goes to a committee. The committee has a name I am not allowed to share but I can tell you it meets quarterly and the conference room has a credenza with bottled water that is sparkling because someone once put still water in the room and a managing director sent an email about it that was longer than most of my surveillance reports. The committee reviews my flags. The committee has reviewed all of my flags. Here is the complete record of actions taken on my flags in 2026: Reviewed. That's it. "Reviewed" is a status. In compliance, a status is the absence of an action that has been given a name so it looks like one. Let me show you my flags. March 9th. Someone bet millions on oil falling at 18:29 GMT. Forty-seven minutes later, a CBS reporter posted that the President said the Iran war was "very complete, pretty much." Oil dropped 25%. Forty-seven minutes. I flagged it. March 23rd. Someone sold 5,100 lots of Brent and WTI crude futures between 10:49 and 10:50 GMT. Fourteen minutes later, the President posted on Truth Social about a "COMPLETE AND TOTAL RESOLUTION" to hostilities. Oil dropped 11%. Over 13,000 contracts traded in sixty seconds after the post. Fourteen minutes. I flagged it. April 7th. Someone established a $950 million short position in oil futures at 19:45 GMT. Three hours later, the President declared a two-week ceasefire. Nine hundred and fifty million dollars. I flagged it. April 17th. Someone placed $760 million in bearish bets twenty minutes before Iran's foreign minister confirmed the Strait of Hormuz would reopen. Seven hundred and sixty million. I flagged it. April 21st. The $430 million. Fifteen minutes. I flagged it. That is $2.1 billion in directional oil bets in April alone. Every one of them landed on the correct side of a presidential announcement. Every one of them was placed in a window so narrow you could measure it in bathroom breaks. I flagged every single one. The CFTC chair told a Congressional committee that his organization has "zero tolerance" for fraud and insider trading. I wrote that quote on a Post-it note and stuck it to my right monitor. The one that shows the investigation queue. The investigation queue has not moved since March. Zero tolerance. Zero staff. Zero budget. Zero prosecutions under the STOCK Act since it was signed in 2012. Fourteen years. The law has existed for fourteen years and has been enforced zero times. In compliance, we call that a compliance rate of one hundred percent. No cases filed means no cases lost. You cannot fail an audit you never conduct. We call that excellence. Last month the White House sent an internal email to staff. I was not on the distribution list but I have read reporting on it and I need you to sit with what I am about to say. The email instructed White House staff not to use insider information to place bets on prediction markets. The White House had to send a memo telling its own employees not to insider-trade. I want you to read that sentence again. Not because the instruction was unclear. Because the instruction was necessary. Because someone in the building looked at the same pattern I have been flagging for months on my three monitors and decided the appropriate response was an email. The President's son sits on the advisory board of Kalshi. He is an investor in Polymarket. Both are prediction markets. Both saw accounts created days before U.S. military action. One account. I cannot stop thinking about this account. It was called "Burdensome-Mix." It was created in December. On January 2nd, it placed $32,500 on Venezuela's president being removed from power. On January 3rd, Maduro was seized by U.S. special forces. Burdensome-Mix collected $436,000. Then it changed its username. Then it disappeared. One account is a coincidence. But there were six. Six accounts were created on Polymarket in February. All bet on U.S. strikes on Iran by the 28th. When the President confirmed the strikes, the six accounts collected $1.2 million between them. Five of the six never placed another bet. The sixth went on to correctly predict the ceasefire date and made another $163,000. My surveillance system logged all of this. My system logs everything. My system does not have opinions and neither do I. I generate reports. The reports go to committees. The committees meet quarterly. Between meetings, the windows get shorter and the bets get larger. March 9th: 47 minutes. March 23rd: 14 minutes. April 17th: 20 minutes. April 21st: 15 minutes. The window is compressing. In March, you had time to make coffee between the trade and the announcement. By April, you had time to send a text. By summer, at this rate, the trade and the announcement will be the same event. The spokesman said any implication that administration officials are engaged in insider trading is "baseless and irresponsible reporting." Then the White House sent the email again. I have been in compliance for nineteen years. I have seen insider trading run out of strip mall offices by men who could not spell "derivative." I have seen pump-and-dump schemes coordinated over WhatsApp by people who used their real names. I have seen a man try to manipulate soybean futures from a Panera Bread. I have never seen $2.1 billion in perfectly timed trades across five presidential announcements in a single month go uninvestigated. But I have also never seen a compliance system work this beautifully. Every trade flagged. Every report filed. Every committee briefed. Every quarterly meeting attended. Bottled water: sparkling. Minutes: distributed. Zero prosecutions. As long as the flags go up and the cases don't, my performance review says I am meeting expectations. I am meeting expectations. The system is meeting expectations. The $2.1 billion is meeting expectations. The fourteen-year-old law with zero prosecutions is meeting expectations. The left screen moves. The middle screen moves. The right screen stays perfectly, immaculately still. In my field, we call this price discovery.

This sounds like the modern equivalent of “British anti-aircraft gunners just eat lots of carrots and have excellent eyes… like rabbits!” WW2 disinformation campaign.

I grew up on Walker Texas Ranger. I hope death is ready to get roundhouse kicked in the face. My favorite Chuck Norris facts: 1. When Chuck Norris doesn’t do push ups, he pushes the Earth down 2. The Boogeyman checks his closest for Chuck Norris. 3. If you can see Chuck Norris, he can see you. If you can’t see Chuck Norris, you may be seconds away from death. 4. Chuck Norris doesn’t wear a watch, he decides what time it is. 5. A cobra once bit Chuck Norris. After 5 days of agony, the Cobra finally died. 6. Jack was nimble. Jack was quick. But Jack couldn’t dodge Chuck’s roundhouse kick. 7. Chuck Norris’ diary is called ‘Guinness Book of World Records’ 8. When Chuck Norris stared into the abyss, the abyss looked away. 9. Chuck Norris doesn’t sleep. He waits. 10. Voldemort refers to Chuck Norris as “You know who”.

Every book I read gets a 1-10 rating. Here are the 22 books (so far) to earn a 10/10 rating. 📚🧵

Thomas Massie is going NUCLEAR on Trump’s regime change war in Venezuela. “How did it work out in Cuba, Libya, Iraq, or Syria?” “Do we want another Afghanistan in the Western Hemisphere?” “This is about oil and regime change.” “Previous presidents told us to go to war over WMDs, weapons of mass destruction, that did not exist.” “Now it’s the same playbook, except we’re told that drugs are the WMDs.” “James Madison warned us that in no part of the Constitution is more wisdom to be found than in the clause which confides the question of war and peace to the legislature—not the executive.” “The framers understood a simple truth: to the extent that war-making power devolves to one person, liberty dissolves.” “By escalating toward war, we would predictably create countless refugees.” “Are we prepared to receive swarms of the 25 million Venezuelans who will likely become refugees?” @RepThomasMassie @MassieforKY

My GPT year in summary

AI-designed proteins that survive 150 °C and nanonewton forces Proteins are usually fragile machines. Heat them, pull on them, or send them through a high-temperature sterilization step (like those used in hospitals), and most will unfold and aggregate, losing their function. Yet many natural systems—like muscle titin or spider silk—hint that if you organize β-sheet hydrogen bonds in the right way, you can get remarkable mechanical strength and thermal resilience. Bin Zheng and coauthors take that idea and push it to the extreme. Starting from the titin I27 domain, they use an AI MD pipeline—RFdiffusion for backbone generation, ProteinMPNN for sequence design, ESMFold/AlphaFold2 for structure prediction, and steered/annealing MD for screening—to systematically elongate the force-bearing β strands and maximize backbone hydrogen bonds in a shearing geometry. Across multiple design rounds, they grow the network from 4 to 33 backbone H-bonds, creating a “SuperMyo” series of proteins with unfolding forces above 1,000 pN—roughly 4× stronger than I27 under the same pulling conditions. Remarkably, these proteins not only refold after force, but also retain structure and function after exposure to 150 °C and repeated high-temperature sterilization cycles, and can be used as crosslinkers to make hydrogels that survive those treatments intact. The message is powerful: by combining generative protein design with physics-based simulations, it’s now possible to turn a simple principle—pack as many shear-mode hydrogen bonds as possible into β sheets—into synthetic proteins and materials that rival or surpass nature’s own mechanostable systems, enabling protein-based hydrogels and biomaterials that remain functional under conditions that would normally destroy conventional proteins. Paper: nature.com/articles/s41557-0…

One more thought and then gym time: It took 4,900 lifespans before humans were able to circumnavigate the Earth, in a wooden ship with cloth sails. From there it took 5 more lifespans to land on the Moon, Mars, and escape the solar system.

This is absolutely incredible tech. Image a blind person can now put on a pair of stylist Warby Parker glasses (cameras in frame) and be able to see perfectly. The retinal implant is 2mm x 2mm x 0.1mm You likely wouldn’t even know the person you are talking to was biologically blind. youtube.com/shorts/7a2DAXiTn…

Gemini 2.5 Pro is the first model that successfully solved this riddle.

Quick update. Gemini 2.5 Pro is the first model to successfully answer this math problem. (Designed specifically to leverage things humans are good at and AI is poor at)

Excellent post by @SparksRemarks on “To Do” lists and how to reframe into “Opportunities”. forcingfunction.com/articles…

How to increase agency *and* have fun: Get a giant whiteboard in your home.