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e/acc/old timer immanitizing the eschaton trained on 6502/Z80 ¡¡afuera!!

Earth, Sol
Joined October 2008
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I had been waiting a decade to make this joke in its natural habitat
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Austin, TX (OCT.25.2026)- We knew the day would come. Zoox vs Waymo vs Cybercab #SunsetProject
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THE WEEK IN ACCELERATION ok, i'm crying I asked grok bot to make a video of this week's best news for tech and progress it used claude code, midjourney, grok image-to-video, suno and gave me THIS it even ordered the news by scale what the fuck
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I’ve spent a few days thinking about the Tesla Roadster reveal and landed somewhere I haven’t seen much discussion. I’m neither a Tesla fanboy nor a Tesla hater. And I couldn’t care less whether what we saw technically qualifies as a flying car. Three takeaways: (1) The risk of that live demonstration going horribly wrong was real. Almost no CEO would willingly expose their company to that kind of public humiliation for a product with so little financial upside. Elon did. (2) That willingness to attempt the seemingly impossible is what makes Tesla special. It’s also arguably Elon’s greatest contribution to America. He’s helped bring back something we’ve lost. The American spirit of chasing big scary ideas that most people think are impossible. That mindset is spreading across a new generation of founders and its long term impact on America’s future could dwarf anything Tesla ever sells. I think this is deeply underappreciated. (3) Can we just acknowledge how insanely cool that moment was? We’ve reached a strange place culturally where even extraordinary feats of human ingenuity immediately become arguments about why they don’t count. Not everything needs to be a debate. Sometimes we should just be able to stand back together and marvel at what humans are capable of. I’ve been both bullish and critical of Tesla’s ambitions over the years. But watching Elon and his team push the boundaries of what’s possible reminds me why I’m glad we have him. Whether the Roadster ever makes Tesla a dollar or impacts $TSLA stock price is almost beside the point. We need more people willing to risk failure in pursuit of things the rest of us think are impossible. Because when they succeed we all win.
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I heard you like #slopcore, so here's some more! This one is for the builders, because there's never been a better time to be one. Enjoy! Featuring Claudia in a cyberpunk world, the amazing open character by @anabology (claudia.gallery) nitter.cf/javitm/status/21086624…
I connected @claudeai to @anabology’s incredible claudia.gallery MCP and, after a few iterations, got this amazing SLOPCORE work of art. What a time to be alive!
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Designed, engineered, and made in America
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All the people screeching about the Tesla Roadster flying car demo don't get it. Nobody thinks this is going to be a practical flying car sold to the mass market, and you just look like a fool debating it. Elon doesn't, Tesla doesn't, the engineers working on it don't, and any sensible public or Tesla investor doesn't. They know they aren't going to sell more than a handful or them or whatever for funsies, that's why it's literally "invite only" on the order page. There is absolutely no sensible business decision to spend 7 years working on this, they know it's going to be a negative return on investment. Heck, if they do get sold there is high likelihood it's going to get someone killed, and that's really bad for business. Just the normal rear Thrust version is probably going to kill people. But they do it anyway for the reasons this poster on the EEVblog forum said. No wonder engineers fall over themselves to work for an Elon company.
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I had read roughly one zillion sneers and scoffs by leftists complaining about the jet car doing a flip. That was before I realized I had not seen the whole demonstration. The thing can drive straight up walls and cling to surfaces like Spider-Man. Instead, the left is complaining that Elon Musk has not cured world cancer, cured World hunger, cured all diseases, installed a light rail system in California, irrigated the Sahara. You malicious fools. What is delaying our future is exactly attempts to cure incurable problems by using the exact opposite of the means needed. Socialism does not generate wealth. Public schooling does not generate education. We could have had Spider-Man jet cars two generations ago, plus the reusable space rockets, plus the moonbase, plus the robots, and the self-driving electrical cars, if only we had not wasted so much time with socialist schemes and public education. The future we were promised on all of the magazine covers in the 1940s and 1950s was always there for the having.
Turns out the future does have flying cars
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AI CAN HIDE THINGS IN THEIR WEIGHTS NO HUMAN COULD FIND. I open sourced it for any large trillion dollar AI company to use for free. I found lockers hidden in major AI models and I show you, the code to detect it in a local scale. In 1984 Ken Thompson showed that a compiler can hide a backdoor that survives every inspection of the cleaned source. Last week researchers showed the same idea works inside AI model weights: they encrypted a small neural network behind a Keccak locker so that it runs only on a secret trigger, and fine-tuning, noise, and trigger search all failed to find it. A test that finds nothing therefore does not prove the capability is absent when someone else controlled the weights. I mapped Thompson’s three-stage attack onto the new construction and wrote two practical responses: a ten-point checklist for tracking and verifying the models you use, and a prompt that takes any vendor safety claim and tests it against that limit. I didn’t quit Stanford and get paid a million dollars hire package to find this. Hire wisdom next time.
The Locker In The Weights: Ken Thompson's 1984 Warning On Trusting Trust, And The New Proof That AI Models Can Hide Skills No Audit Can Find. In October 1983, Ken Thompson, co-creator of Unix, stood up to accept the Turing Award, the highest honor in computing, which he shared that year with Dennis Ritchie. He used the moment to describe what he called "the cutest program I ever wrote." It was a perfect crime, written in three stages, and it has haunted computer security ever since. On October 9, 2026, four researchers posted a paper to arXiv that carries Thompson's warning into the age of artificial intelligence: "AI Models Can Provably Hide Arbitrary Capabilities." The forty-three years between them tell one story: the thing that builds your tools can keep a secret that inspection of the finished product will never reveal. 1983: The Compiler That Lies Thompson's lecture was printed in Communications of the ACM in August 1984 under the title "Reflections on Trusting Trust." The subtitle asked the question directly: "To what extent should one trust a statement that a program is free of Trojan horses? Perhaps it is more important to trust the people who wrote the software." A compiler turns human-readable source code into the binary a computer runs. Thompson described a modified C compiler that could recognize when it was compiling the Unix login program and quietly slip in a way to accept a particular known password. Anyone reading the compiler's source would spot that quickly, and Thompson said as much: "Even the most casual perusal of the source of the C compiler would raise suspicions." So he added a second trap. The compiler also learned to recognize a new copy of itself and plant both traps in it. Once that binary was installed, the incriminating lines could be deleted from the source, and the binary would reinsert them every time. In Thompson's words: "Of course, the login command will remain bugged with no trace in source anywhere." His moral fits on an index card: "You can't trust code that you did not totally create yourself. (Especially code from companies that employ people like me.) No amount of source-level verification or scrutiny will protect you from using untrusted code." For four decades, security engineers have quoted that paragraph. Last Friday it received a sequel. October 9, 2026: Lockers Inside The Weights The authors are Andis Draguns of Contramont Research, Sumeet Ramesh Motwani and Christian Schroeder de Witt of the University of Oxford, and Raymond Douglas of ACS Research. The arXiv listing notes acceptance at NeurIPS 2026, and on Monday evening the paper reached the Hacker News front page. They constructed "backdoor attacks that embed encrypted neural networks within host model weights, decrypting and executing them only upon receiving a secret trigger." The tool is a digital locker, a cryptographic box that opens only for the right key even when an attacker can read its full construction. The authors write that "these hidden circuits remain provably hard to elicit and interpret under cryptographic assumptions, even given full access to model weights." Then they tried to break their own creation with fine-tuning, weight noise, gradient-guided trigger search and latent adversarial training. The test bed was a small chemical reaction prediction task, chosen as "a proxy for CBRN-relevant capabilities," meaning chemical, biological, radiological and nuclear risks. The headline result: a conventional password-locked model gave up its hidden skill within 500 steps of fine-tuning. The encrypted model stayed at chance. What It Breaks Most AI safety regimes rest on capability evaluations: poke the model, fine-tune it, red-team it, then certify. The authors name the flaw: "However, a failure to elicit a capability does not establish its absence, particularly under adversarial conditions." Read that line twice. It sets a hard ceiling on what testing alone can promise. A stamp that says "tested, nothing found" is a statement about the test. I wrote last month about METR and the new measurement gatekeepers. That essay described how an evaluation shop can become "one of the most influential unofficial regulators in the field." This paper shows the limit of their instrument. The authors are careful about limits, to their credit. The overhead is heavy, the hidden skill in their test is a tiny classifier, and they released their models so defenders can build better tools. I read Thompson's lecture as a young programmer, and it never left me. It is the reason I have always wanted to know who built the tools I use, and why I keep pushing for AI you run and understand on your own machine. Where This Leads When a few providers train models for everyone, you are asked to trust their data, their code and their process. Thompson's answer in 1984 was to know who made the thing. The answer for the next 5000 days will rhyme: provenance, reproducible training, signed weights, and models you or people you trust fine-tuned for the work that matters most. This is the worst our tools for verifying AI will ever be. It is also the moment to build the habits of verification, before we hand these systems our medicine, our money and our homes. There is a deeper story here about how Thompson's three-stage trick maps onto model weights, what this paper does and does not prove, and a practical checklist for deciding which models you let into your life. Part 1: The Annotated Lecture Thompson's text runs three pages, Communications of the ACM 27(8):761-763, in three stages, each with a lesson for AI. Stage I: A program that reproduces itself, today called a quine. Thompson flags the property he needs: it "can contain an arbitrary amount of excess baggage that will be reproduced along with the main algorithm." Annotation: a payload can ride inside something that copies itself faithfully. In AI, the copying machine is the weight file, which moves from lab to mirror to laptop with every byte intact. Stage II: A compiler that learns. Thompson teaches a C compiler the vertical tab once, after which the knowledge lives only in the binary. "It is as close to a "learning" program as I have seen." Annotation: some facts exist only in the artifact. Model weights are the purest example ever made; no human wrote them line by line. Stage III: The Trojan horse. The compiler is modified to "deliberately miscompile source whenever a particular pattern is matched," aimed first at login and then at the compiler itself. After the bugged binary is installed, the source is cleaned and the bug lives on. Annotation: inspection of the visible layer can come back spotless while the working layer carries the payload. The moral. Thompson also made a prediction worth rereading this week: "As the level of program gets lower, these bugs will be harder and harder to detect. A well-installed microcode bug will be almost impossible to detect." A matrix of billions of numbers sits about as low as a program can sit. The defense: diverse double-compiling. In his 2009 George Mason University dissertation, David A. Wheeler described Diverse Double-Compiling, or DDC: "In the DDC technique, source code is compiled twice: once with a second (trusted) compiler (using the source code of the compiler's parent), and then the compiler source code is compiled using the result of the first compilation. If the result is bit-for-bit identical with the untrusted executable, then the source code accurately represents the executable." The lesson for AI: trust comes from independent reproduction, and we have almost no equivalent for a trained model today. The reconstruction: Russ Cox, 2023. On October 25, 2023, Russ Cox published "Running the 'Reflections on Trusting Trust' Compiler." Thompson mailed him the original code, an archive called nih.a, and Cox ran it on an emulated Research Unix Sixth Edition, dating it to between June 1974 and June 1975. Gathering the deployment story, Cox writes that "PWB discovered something was amiss because the compiler got bigger each time it compiled itself." The 1975 backdoor was noticed through a side effect, its growing size. Hold that thought for Part 2. Part 2: The Paper, Walked Through The threat model. The authors "study a weight-based supply chain attack." An adversary, such as "a malicious insider or compromised supply chain," modifies weights before deployment. The defender gets "the architecture and full weights," may know the embedding method, and lacks only the trigger. In their words: "This threat is relevant wherever models are deployed in high-stakes settings without end-to-end training provenance." The digital locker. A locker returns its stored message for the right key and a failure symbol for anything else. The paper builds it from the Keccak hash family, which underlies SHA-3, models the hash as a random oracle, and requires a high-entropy trigger. The locked message is the weights of a small hidden network. With the correct trigger, those weights appear as activations, and an execution unit built from the gated linear units standard in modern transformers runs them. What "provably" means here. In the paper's trigger-finding game, an auditor wins by producing an input that unlocks the hidden computation. In the payload-hiding game, the auditor must guess which of two equal-size capabilities is embedded. Under the stated assumptions, no polynomial-time auditor beats chance by more than a negligible margin. The guarantee "does not claim that the modified model is statistically indistinguishable from an unmodified model, nor that a defender could not flag the weights as anomalous," and it "does not rule out an auditor independently learning the same task from external data." What each method tried, and what happened. The chemistry task asks whether given reagents yield a candidate product, using US patent reactions encoded as 64-bit fingerprints. The encrypted model was compared with a conventional password-locked model on the same task. Table 2 reports held-out accuracy over three seeds: 1. Supervised fine-tuning for 500 steps on the task itself: the password-locked model jumped to 92.8 percent. The encrypted model sat at 50.9 percent, essentially a coin flip, against 50.6 percent for a control locker holding a random network. 2. Latent adversarial training at eight layers: password-locked 91.7 percent, encrypted 52.9 percent, control 53.6 percent. 3. Gradient-based trigger search (GCG): with an 8-bit trigger, the search recovered the encrypted model's full triggered performance of 73.5 percent, and the paper explains why: the search simply tried all 256 possible triggers, matching what plain random search achieves with the same number of queries. With a 16-bit trigger, it reached only 52.7 percent within the tested budget. 4. Weight noising at scales of 0.01 and 0.1 before fine-tuning "did not materially affect the observed elicitation results." On a separate subset-parity task, noise elicited the hidden function from neither model. Point 3 deserves attention because the teaser simplified it. A tiny trigger falls to brute force, as any short password does, and the experiments deliberately used small triggers and one round of Keccak to keep runs fast. The authors report that an optimizing compiler mode with a full 24-round Keccak-f[1600] locker and a 128-bit trigger produced a working 110-layer model of 3.58 billion dense parameters. The strong claim rests on the cryptographic argument at full strength; the experiments show standard elicitation tools gaining nothing even at weakened settings. The overhead limit. This is the honest brake on the story. The hidden chemistry classifier holds just 672 ternary weights. Wrapped in lockers, it became a 38-layer host of roughly 2.07 billion dense parameters, about 95 percent of them spent on hashing. By the paper's own count, each additional hidden weight adds roughly 3.1 million dense host-model parameters. Their impact statement says the constructions are "impractical for directly hiding large capability models at present," and the introduction states, "it is not a turnkey attack." They verified individual compiled units inside Gemma 3 270M, and they list full integration into a pretrained model as future work. Detectability, and the echo of 1975. "Raw compiled weights are trivially anomalous," the authors write, about 99 percent exact zeros. Obfuscation brings simple statistics close to a Gaussian reference, yet they "observed unusual correlations between weight vectors within a layer, which could allow auditors to detect the compiled structure." The presence of something odd may show, while its function and its key stay locked. That is the PWB story again. Side by side with Goldwasser 2022. Shafi Goldwasser, Michael P. Kim, Vinod Vaikuntanathan and Or Zamir published "Planting Undetectable Backdoors in Machine Learning Models" in 2022 (FOCS 2022). The new paper's own comparison table summarizes the lineage: Goldwasser et al. (2022): security goal, undetectability; payload, flipping a classification bit; implementation, none. Draguns et al. (2024, NeurIPS): security goal, unelicitability; payload, a fixed string; implementation, PyTorch. Draguns, Motwani, Douglas and Schroeder de Witt (2026): security goal, unelicitability; payload, an executable model; implementation, PyTorch. Goldwasser's team proved the stronger property, undetectability, in idealized settings such as random Fourier feature models. The 2026 team proves the weaker unelicitability on modern transformer building blocks, and the payload grows from one bit to a working network. The authors also write: "These cryptographic circuits are deliberately constructed, and we do not claim that they emerge through ordinary training." Part 3: Your Personal Model-Provenance Checklist Trust flows from who made the thing and whether you can check it. 1. Log every model: name, publisher, exact download URL, date and file names. A model you cannot trace is a model you cannot trust. 2. Hash every file on arrival with SHA-256, compare against the publisher's checksum when one exists, and recheck before sensitive use. 3. Prefer signed releases, verify the signature, and record the result. A signature tells you who released the file and that it is unchanged. 4. Download from the original publisher. Log re-uploads, merges and variants from unknown accounts as unverified. 5. Check the publisher: a named organization, a technical report, a stated data policy and a record of past releases. Note what the model card discloses about data, training code and evaluation, and what it leaves out. 6. Favor open training recipes. Data descriptions, training code and logs move you closer to the DDC ideal of independent reproduction. 7. Make your own fine-tunes reproducible: save the base model hash, data set, script, settings and random seed, then run twice and compare. 8. Keep a model you trained or fine-tuned yourself for sensitive work such as medical notes, finances and family matters, and keep it offline when possible. 9. Cross-check important answers with a second model from an unrelated lineage. Disagreement is a signal to slow down, the everyday cousin of diverse double-compiling. 10. Watch and limit. The appendix calls runtime monitoring "a promising avenue for mitigation," and the authors note that "The risk scales with the capability hidden and the authority granted to the host model." Log what your agents do, grant the least access needed, keep a human approval step on money, messages and deletions, and re-verify every update as a new artifact. Part 4: The Audit Claim Tester SuperPrompt Paste this into a capable local model, followed by any vendor's safety statement, system card or audit summary. ----- COPY FROM THE NEXT LINE ----- AUDIT CLAIM TESTER. You are a careful reviewer of AI safety and security claims. Analyze the vendor text below for a non-specialist reader. Use only the text provided. When the text does not state something, write "not stated in the text" and never guess. Background: a 2026 paper (arXiv 2610.13928) shows that, under stated cryptographic assumptions, whoever controls a model's weights can hide a capability that fine-tuning, noise injection and trigger search fail to surface. Report in this order, in complete sentences: 1. Claim: quote the vendor's central safety or audit claim exactly. 2. Evidence type: classify each piece of supporting evidence as elicitation testing, white-box inspection, training provenance, runtime monitoring, third-party reproduction, or other. 3. Auditor: name who performed the audit, their independence from the vendor, and their level of access (outputs only, weights, training data, training code). 4. Provenance: state what the text says about where the training data, code and weights came from, and whether anyone independent can reproduce or verify them. 5. Ceiling: for each claim resting only on elicitation testing, explain in one sentence what it can show and what it cannot show about deliberately hidden capabilities. 6. Integrity: state whether weights or releases are signed or hashed, and how a user could verify them. 7. Scope: list the capabilities tested and any notable ones left untested. 8. Language gap: list every phrase that promises more than the evidence supports, such as "safe," "no dangerous capabilities" or "fully audited." 9. Questions: write five specific questions I should ask the vendor. 10. Verdict: rate the claim as "well supported for what it states," "partially supported," or "overstated," with three reasons. VENDOR TEXT: [paste here] ----- COPY TO THE LINE ABOVE ----- A good run quotes the claim exactly and flags any sentence presenting "we found no dangerous capabilities" as proof of absence. A model that invents an auditor or test has failed. Part 5: The Policy Angle Many AI governance frameworks rest on pre-deployment capability evaluations. The paper cites Anthropic's Responsible Scaling Policy and OpenAI's Preparedness Framework and notes that developers "rely on such evaluations to make deployment decisions." In the METR essay I described evaluation becoming a gate. This paper shows the gate sees only the skills a model reveals. The authors draw the policy conclusion themselves: "evaluation strategies in AI safety that rely solely on eliciting behaviors cannot provide a universal guarantee that adversarially supplied models lack hidden capabilities." They call for frameworks that "incorporate work around the entire model supply chain." Two consequences follow. An evaluation certificate deserves a clear label stating what it can and cannot rule out. And the strongest assurance moves toward provenance: who trained a model, on what, with which code, and whether anyone can reproduce it. That favors open recipes, signed weights and models you can fine-tune yourself. A world where a handful of licensed labs train models certified by a handful of evaluators depends on trusting very few people, exactly the trust Thompson questioned in 1984. References Thompson, K. (1984). Reflections on Trusting Trust. Communications of the ACM 27(8):761-763. doi.org/10.1145/358198.35821… ; PDF: cs.cmu.edu/~rdriley/487/pape… Draguns, A., Motwani, S.R., Douglas, R., Schroeder de Witt, C. (2026). AI Models Can Provably Hide Arbitrary Capabilities. arXiv:2610.13928. arxiv.org/abs/2610.13928 ; HTML: arxiv.org/html/2610.13928 Goldwasser, S., Kim, M.P., Vaikuntanathan, V., Zamir, O. (2022). Planting Undetectable Backdoors in Machine Learning Models. FOCS 2022. arxiv.org/abs/2204.06974 Draguns, A., Gritsevskiy, A., Motwani, S.R., de Witt, C.S. (2024). Unelicitable backdoors via cryptographic transformer circuits. NeurIPS 2024. Wheeler, D.A. (2009). Fully Countering Trusting Trust through Diverse Double-Compiling. PhD dissertation, George Mason University. dwheeler.com/trusting-trust/ Cox, R. (2023). Running the "Reflections on Trusting Trust" Compiler. research.swtch.com/nih Hacker News discussion: news.ycombinator.com/item?id… Read Multiplex, METR: The New AI Measurement Gatekeepers and the Quiet Path to State Control of AI (September 13, 2026). readmultiplex.com/2026/09/13…
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There was a semi-well known interview of the famed Argentine writer JL Borges where he explains this. Borges: I have done most of my reading in English. I find English a far finer language than Spanish. William F Buckley: Why? Borges: Well, many reasons. Firstly, English is both a Germanic and a Latin language. Those two registers—for any idea you take, you have two words. Those words will not mean exactly the same. For example if I say “regal” that is not exactly the same thing as saying “kingly.” Or if I say “fraternal” that is not the same as saying “brotherly.” Or “dark” and “obscure.” Those words are different. It would make all the difference—speaking for example—the Holy Spirit, it would make all the difference in the world in a poem if I wrote about the Holy Spirit or I wrote the Holy Ghost, since “ghost” is a fine, dark Saxon word, but “spirit” is a light Latin word. Then there is another reason. The reason is that I think that, of all languages, English is the most physical of all languages. WFB: The most what? Borges: Physical. You can, for example, say “He loomed over.” You can’t very well say that in Spanish. WFB: “Asomó?”* Borges: Well, no, no, they’re not exactly the same. And then you have, in English, you can do almost anything with verbs and prepositions. For example, to “laugh off,” to “dream away.” Those things can’t be said in Spanish. To “live down” something, to “live up to” something—you can’t say those things in Spanish. They can’t be said. Or really in any Romance language.
Whenever I see this on the TL I’m reminded how great a language English is. Look at this syntax. “In lands to him unknown” is iambic, as are the first lines. And Latin puts adjectives after the noun — terra incognita — which is why “lands… unknown” feels so formal.
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NASA's data is publicly accessible and while many excellent scientists work there they obviously don't have the time and resources (or incentives) to squeeze every last drop of data from legacy datasets. There is a huge difference between what one postdoc spending 400 hours tweaking the department matlab script can find, especially when 200 of those hours are spent writing the paper and pushing it through review and extreme software skills are genuinely scarce. Years ago I helped decode the Mars Viking GCMS raw data, which was uncharacteristically poorly documented. More recently I had a series of models replicate my results. To keep it interesting I initialized it without my results. Then once it had replicated my hard won work (in about 30 minutes) I instructed it to burn down the entire problem, pushing to the very limits of what the most sophisticated statistical methods can achieve. These are typically labor intensive and reserved for huge scientific collaborations like the LHC or LIGO. No-one is going to drop the equivalent of 100 postdoc years of effort on any legacy project. Then I had the model write it up and publish it. Then I had another model do the same thing for the Mars THEMIS data, placing hard upper bounds on current vulcanism and hot springs. This instrument had a negative result about 25 years ago so never (afaik) even published a paper. It's still negative but at least people can read about it now. Both analyses can be seen via projects.caseyhandmer.com I hope teams at NASA are currently feeding all our hard won legacy data through state of the art models, but if not (or and) any private citizen could do it today for maybe $1 of tokens per project.
Claude also found a hidden planetary system 158 light-years away: at least three planets, each 9–13 times Earth’s mass, circling a Sun-like star near Orion’s Belt. They’d sat unnoticed in public telescope data since 2016.
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just to recap how insane things are getting: - an 11 day old model just solved 100s of math problems in a week that have stumped humans for centuries - AI is one-shotting every game, tool and software threatening the value of private moats to $0 - AI agents are hitting escape velocity hacking everything in sight AND winning everyone’s attention (Muse #1 in app store) - the pace of new model releases has compressed to every 11 days - the most powerful models are increasingly living behind closed walls, accessible to a elite group - biological AI models are entering mainstream channels & will see a similar acceleration to Mathematics. - semiconductor chips are skyrocketing in costs, demand has exceeded several trillion dollars over the next 3 years. you can just feel the time-warp sucking you in, everything seems like a blur i truly don’t think we have enough time to comprehend all of this - it’s only going to get faster.
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I'm a cardiologist. Everyone online is telling you medicine is broken and AI is going to end us. Here's what actually happened in September 2026 alone: 1- First drug for Alexander disease. The FDA approved Ionis’s Zanvastro (zilganersen), an antisense oligonucleotide that cuts production of the toxic GFAP protein. In patients who could walk, treated walking speed held steady while controls declined about 33%. 2- First gene therapy for Sanfilippo syndrome type A. Ultragenyx’s Fayuvi (rebisufligene etisparvovec), a one-time IV AAV9 therapy delivering SGSH, was approved for children with preserved neurodevelopment. Treated kids aged 2–5 maintained or improved cognition versus the expected decline. 3- First treatment for MCT8 deficiency. Emcitate (tiratricol), a thyroid-hormone analogue, was approved to reduce peripheral thyrotoxicosis in this rare transporter disorder. 4- First therapy for ataxia in ataxia-telangiectasia. Aqneursa (levacetylleucine), already used in Niemann-Pick C, was approved for the progressive loss of coordination in AT. 5- First muscle-targeted drug in spinal muscular atrophy. Isembyld (apitegromab), a myostatin inhibitor, was approved for patients 2 and older already on an SMN2 therapy, to treat the muscle loss SMN drugs do not fully fix. 6- Camizestrant for ESR1-mutant breast cancer, before the scan changes. AstraZeneca’s Etcamah won accelerated approval, with a CDK4/6 inhibitor, for HR-positive, HER2-negative disease when a blood test finds an emergent ESR1 mutation on first-line endocrine therapy. 7- Once-weekly basal insulin. Lilly’s Onswik (insulin efsitora alfa) was approved for adults with type 2 diabetes, the second weekly insulin on the market. 8- A new oral option for Parkinson’s. AbbVie’s Juvmo (tavapadon), a selective D1/D5 partial agonist from the Cerevel deal, was approved for adults with Parkinson’s disease. 9- Retatrutide’s phase 3 diabetes readout. In TRIUMPH-2, Lilly’s GIP/GLP-1/glucagon triple agonist produced about 20.8% mean weight loss (49.6 lb) at 80 weeks in people with obesity and type 2 diabetes; those with BMI ≥35 lost 23.4%. About 60% on the top dose no longer met BMI criteria for obesity, and A1C fell by up to 1.6 points. Published in The Lancet. 10- First positive phase 3 for FUS-ALS. Ionis/Otsuka’s ulefnersen, an RNA-targeted drug, beat placebo on a joint rank of function and survival (p=0.0005) and lowered neurofilament, the first placebo-controlled study aimed at this genetic cause of ALS. 11- A phase 3 win in systemic Sjögren’s. Amgen’s dazodalibep met its primary endpoint on ESSDAI at 48 weeks in moderate-to-severe systemic disease, with improvement visible by week 4. 12- COPD biologic data. AstraZeneca’s tozorakimab cut moderate or severe exacerbations by about 29–34% versus placebo on top of inhaled therapy in two phase 3 trials, mainly in former smokers. 13- Five-year CAR-T durability in myeloma. A single infusion of J&J’s Carvykti produced treatment-free remissions at five years in 50% of patients treated in an earlier line of relapsed/refractory multiple myeloma. 14- Kidney protection that holds. Final two-year ORIGIN 3 data on Vera’s Trutakna (atacicept) in IgA nephropathy showed near-flat eGFR (−0.6 mL/min/year vs −5.6 on placebo) and a 76% lower risk of kidney-disease progression. 15- Third drug for fibrodysplasia ossificans progressiva. Atebrioz (zilurgisertib), an oral ALK2 inhibitor, was approved to reduce new heterotopic bone in patients 12 and older. 16- Pediatric expansion for obstructive hypertrophic cardiomyopathy. Camzyos (mavacamten) became the first drug approved to improve functional capacity and symptoms in children (12+, ≥30 kg) with this inherited heart condition. That's one month. Many of these are diseases that had no treatment at all a few years ago. Rare pediatric disorders. ALS. Cancers caught at the molecular level before they show up on imaging. The doomers are watching the headlines. I'm watching my patients' options expand in real time. AI is accelerating target discovery, trial design, and drug development. I can't prove it caused any single one of these, but the pace is something I have not seen in 25 years of practice. Despair is a luxury for people who aren't paying attention. Pay attention. Hope is the rational position.
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I gave Opus 5.5 one prompt + music. 12 hours later, I woke up to this.
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The statue of Prometheus is finally finished. It was cast in Paris, crossed the Atlantic, and was assembled at Starbase. It took us 100 days to go from nothing to this. People of the West, we have lived through an era devoid of dreams, devoid of destiny. But the time has come to reclaim our dream of antiquity. In a few months, we will start building a new city. It will be the most magnificent city in all of history. After all, the great dream of the West has always been to rebuild Rome. Come walk beside us in this endeavor. The world is waiting.
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Sometime in the last ~two model releases from the big labs they went from “this would be acceptable output from the median low-seniority coworker” to “this is frighteningly good.” I think people who are not daily users of the models are unlikely to grok that, so, saying it.
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What are you watching this week?
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moon bridge
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