David Stănete

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David Stănete

David Stănete

@stanete

tech + bjj. Head of Engineering https://t.co/csoudY0Ige. I write the code

Katılım Aralık 2009
170 Takip Edilen4.2K Takipçiler
David Stănete retweetledi
Afshine Emrani  MD FACC
Afshine Emrani MD FACC@afshineemrani·
I'm a cardiologist. Everyone is sharing this study as a skin story. They're burying the part that matters. Scientists took the aorta of a 75-year-old donor, applied a single engineered enzyme, and stripped away more than 70% of the molecular damage — bringing it down to the levels you'd see in a 30-year-old artery. Published five days ago in Nature Communications. Revel Pharmaceuticals, with Calico and the University of Colorado. Here's what they erased. Sugar reacts with proteins in your body the same way heat browns bread — slowly, over a lifetime. It leaves behind a residue called CML, the most abundant advanced glycation end product in aging tissue. It welds itself onto collagen and elastin in your skin, your eye lens, and your arterial walls. Two things follow. Your arteries stiffen. And CML latches onto a receptor called RAGE, which drives chronic inflammation — the exact fire I've been writing about for months as the engine of heart disease. Since the 1980s this damage was considered permanent. Your body has no enzyme to remove it. Every existing approach only slows new damage from forming. Nothing touched what was already there. So they built an enzyme that doesn't exist in nature. They screened 45,000 protein structures, then ran five rounds of directed evolution across more than 500 million variants until they had CMLase — a molecular lawnmower that oxidizes the CML off the protein and restores the original, healthy lysine underneath. Not patched. Reversed. Over 70% cleared from elderly arterial tissue. Over 55% from elderly skin — below the levels found in 31-year-old skin. 45-78% in lens proteins. The CEO said they expected 20% and were floored. Arterial stiffness drives systolic hypertension, heart failure, and stroke, and I have no drug that reverses it. I can slow the process. I cannot undo it. This paper says undoing it may be possible. The caveats are real and I won't skip them. This was done on donated tissue in a dish, not in a living person. No functional data yet — we don't know if that artery got measurably more elastic. Delivering a large enzyme deep into human tissue is a hard, unsolved problem. Clinical trials are years away. But something considered permanent for forty years just came off human tissue. We spent a century learning to slow aging. Someone finally figured out how to erase it. Thank you @theallinpod @friedberg @chamath @pesottas
The All-In Podcast@theallinpod

Friedberg: New study shows enzyme reverses skin age from 70+ years to 31 Chamath: That’s a $2T market. Did Scientists Just Discover How to Reverse Skin Aging!? “CML is kind of the predominant molecule that gets formed in this extracellular matrix that's driving aging, and nothing breaks it down. So these scientists set out to try and create an enzyme, an enzyme is a protein that breaks something down, that can break down CML. And so these guys kind of went out and they took the target, which is CML, and tried to figure out, ‘Okay, how do we actually degrade CML, clear that extracellular matrix, and reverse aging?’ They started to test it on the proteins that we would find in our body, casein, collagen, retinal proteins, which are in your eye, hemoglobin, and they were able to get rid of 52 to 97% of the CML, just degrade it away. And then they found several sites where they were able to degrade over 90%. And then they took actual human skin from elderly patients that had donated their skin, and they put this enzyme onto that skin, and they were able to eliminate 55% of the CML on the skin, basically reverse the skin's age down to the age of a 31-year-old, this is from greater than 70-year-old patients, just by putting this enzyme on the skin. And so it's kind of a groundbreaking demonstration of combination of AlphaFold, what's called directed evolution, where you change the order of the DNA that changes the structure of the protein to test different proteins, do high throughput screening, and ultimately make a novel protein that doesn't exist in nature today that can do something pretty profound for human health.” Chamath: “It will be a trillion-dollar market. If you can create a cream…” Friedberg: “I mean, dude, if you could put this enzyme literally on your skin and have it absorb in…” Chamath: “Game over. That alone is $2 trillion.”

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Celine Halioua
Celine Halioua@celinehalioua·
what's the least midwit model for iterating on leadership/management/company strategy topics?
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David Stănete
David Stănete@stanete·
It’s the same for engineering
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David Stănete retweetledi
Peter Yang
Peter Yang@petergyang·
I think AI psychosis (trying to make sure your agents are working all the time) is probably a worse addiction than social media.
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Chamath Palihapitiya
On August 2 the EU's AI Act may begin enforcing its transparency rules, with fines reaching three percent of global revenue for the model providers and application developers who cannot show how their systems were built and trained and don’t properly disclose where AI exists. AI used in hiring, lending, medical diagnosis, law enforcement, education, or critical infrastructure faces strict requirements. The reflexive reaction could be that AI may be too risky for regulated industries. But that would be backwards. What a regulator needs is a record: which requirement a system satisfies, what has changed, when and what test proves it still holds. An old, legacy system written years ago by contractors who have since moved on cannot produce that record at all. Most companies are already running this way. But software built today - like through our Software Factory - can generate that trail as it works, and can then hand over records and audit trails on demand. The opportunity now is to use AI to rebuild all of the old, dysfunctional software that exists in companies around the world into systems that are much cheaper, simpler and that you can actually audit. Learn more here: 8090.ai
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David Stănete
David Stănete@stanete·
@SeanSankerJr Not only programming languages but freaking everything related to tech excellence, architecture, system design, SRE, etc. Damn even agile and management 🥲
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Dillon Mulroy
Dillon Mulroy@dillon_mulroy·
i wonder if as agents become more and more common place we'll also see the rise of HATEOAS style link relations in APIs outside of MCP servers for natural discovery of data and actions
Dillon Mulroy tweet media
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Joscha Bach
Joscha Bach@Plinz·
LLMs tend to be terrible tools for getting life advice from an external perspective, because they are usually biased by the user (or developer) expectations they anticipate
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The Pragmatic Engineer
The Pragmatic Engineer@Pragmatic_Eng·
You can only vibe-code the tip of the iceberg. @KentBeck, creator of TDD & XP, on why there’s more to building a product than the part you can see: “You're paying for some service. You think I could vibe code something better. And so you do, but you only solve part of the problem. This is the iceberg - you can vibe code the part of the iceberg that you can see. I was at Gusto for three years. It does small business payroll. Somebody said, well, ‘I just asked Claude: this many hours at this rate, I'm in this tax bracket, what should my paycheck be? And it tells me all the numbers. I don't need Gusto anymore.’ Go ahead, run your own payroll for a quarter and then figure out all of the reports you need to submit to the various tax agencies in different states. There's so much that goes on to correctly, compliantly execute payroll. So we're going to see people get into situations where they vibe code the tip of the iceberg, throw away the rest of the iceberg, and get in trouble because they don't know what to do. They get to these downstream problems they didn't even know existed.”
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David Stănete
David Stănete@stanete·
Estoy buscando estudios tipo software crafters (lo que era @goKarumi antes) que estén experimentando con agentes para un proyecto dentro de unos meses. (la movida es que tienen que tener sede fiscal en Madrid). Os agradecería recomendaciones 🙏
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David Stănete
David Stănete@stanete·
@Jera_Value Nunca he visto esto (ni escuchado). Hay mucho “programar pa ná, programar pa nadie” eso sí (pero eso no es sólo en España)
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Jera ⛩
Jera ⛩@Jera_Value·
A día de hoy sigo sin explicarme como en España hay tanto desarrollador de software que no hace nada. Tengo a muchos conocidos que les pagan por prácticamente no hacer nada. Y la empresa no se los quita de en medio. Un completo despilfarro. Durante años. No sé si es generalizado de todos los trabajos o específico de software. Entiendo que, con la IA, esto no puede durar mucho más, ¿no?
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javi santana
javi santana@javisantana·
Hace unos días he estado en un evento de emprendedores (organizado por itnig) y hablé con bastantes founders. Puedo oler el bullshit a distancia, 3 frases y ya sé que no estás vendiendo lo que toca ni cómo toca, sé que te estás contratando a golpe de talonario sin sentido, has levantado ronda y no sabes muy bien para que y, especialmente, que me estás vendiendo la mentira que te estás contando para convencerte de que te va genial. Lo sé porque he hecho lo mismo, es como cuando ves a tu hijo pequeño poner excusas tontas, las mismas que tú ponías cuando eras niño. Obviamente yo no digo nada y sigo con la conversación (no doy consejos si no me pagan) pero todo se desmorona poco a poco cuando haces la pregunta “dime la mierda más gorda que tienes ahora mismo” En general cuando habléis con alguien que ha pasado por lo que habéis pasado, no vayáis de sobrados, no somos alguien del VC al que tienes que mantener “caliente”
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Maria Marinova, PhD
Maria Marinova, PhD@m__marinova·
Awesome work and great paper from Aaron and team but one issue with the science communication here. It didn’t reverse skin age for 70 to 31, it reversed levels of CML staining to less than those found in 31-year-old skin (as stated in the paper). They didn’t look at other aspects of skin aging.
The All-In Podcast@theallinpod

Friedberg: New study shows enzyme reverses skin age from 70+ years to 31 Chamath: That’s a $2T market. Did Scientists Just Discover How to Reverse Skin Aging!? “CML is kind of the predominant molecule that gets formed in this extracellular matrix that's driving aging, and nothing breaks it down. So these scientists set out to try and create an enzyme, an enzyme is a protein that breaks something down, that can break down CML. And so these guys kind of went out and they took the target, which is CML, and tried to figure out, ‘Okay, how do we actually degrade CML, clear that extracellular matrix, and reverse aging?’ They started to test it on the proteins that we would find in our body, casein, collagen, retinal proteins, which are in your eye, hemoglobin, and they were able to get rid of 52 to 97% of the CML, just degrade it away. And then they found several sites where they were able to degrade over 90%. And then they took actual human skin from elderly patients that had donated their skin, and they put this enzyme onto that skin, and they were able to eliminate 55% of the CML on the skin, basically reverse the skin's age down to the age of a 31-year-old, this is from greater than 70-year-old patients, just by putting this enzyme on the skin. And so it's kind of a groundbreaking demonstration of combination of AlphaFold, what's called directed evolution, where you change the order of the DNA that changes the structure of the protein to test different proteins, do high throughput screening, and ultimately make a novel protein that doesn't exist in nature today that can do something pretty profound for human health.” Chamath: “It will be a trillion-dollar market. If you can create a cream…” Friedberg: “I mean, dude, if you could put this enzyme literally on your skin and have it absorb in…” Chamath: “Game over. That alone is $2 trillion.”

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David Stănete
David Stănete@stanete·
Otherwise 3 months later, they’ll come back and ask if what you thought was a casual conversation is already finished. And you’d be like… wait what?
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David Stănete
David Stănete@stanete·
If you report to CEOs or execs that don’t write stuff down, do it yourself and share it. You probably don’t have the same understanding about the importance and urgency of what you’re discussing.
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David Stănete
David Stănete@stanete·
. @kieranklaassen would be nice to get an update on compound engineering and what you guys have learned, what works, what doesn’t, etc.and especially how you’ve applied it in products with multiple engineers working on them
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David Stănete
David Stănete@stanete·
@javisantana Well if you’ve been delegating your thinking for months to an LLM is hard to go back. Is as hard as going back to the gym after years of being sedentary.
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David Stănete
David Stănete@stanete·
@antonello Alguien me ha dicho que alguien lo está pagando y que ahí hay conflicto de intereses. ¿Es verdad?
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Antonio Ortiz
Antonio Ortiz@antonello·
Don Linus Torlvads puso el último clavo en el ataúd del escepticismo con la inteligencia artificial en desarrollo software. El mensaje resumido, siempre tan sutil Linus, es que se la pela si eres anti IA: el proyecto del núcleo de Linux no lo es y al que no le guste, aire.
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