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The next frontier in protein design will not be defined by structure alone, but by the capacity to engineer motion as a first-class principle of function. This is because dynamics is where the real biology lives. Foundational work by Karplus, Levitt & Warshel made clear that chemistry cannot be...

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Markus J. Buehler

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89,921 Aufrufe • vor 5 Monaten •via X (Twitter)

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32 Kommentare

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Code: Model weights: Paper:

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

MIT News Article:

Profilbild von LIFE AI
LIFE AIvor 5 Monaten

A shift from structure to dynamics reframes protein design from predicting static folds to engineering motion as function itself. If proteins are dynamic ensembles on rugged energy landscapes, it raises a deeper question: how much of the possible dynamical design space has biology actually explored?

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Biology has only explored a tiny fraction of what is possible, so lots of opportunities for engineers!

Profilbild von S.A. Senchal
S.A. Senchalvor 5 Monaten

Almost like the state space has been reduced by evolution to the most efficient per unit cost to the organism - because ai gives us essentially free compute what's efficient broadens and we get novelty

Profilbild von Hang Zheng
Hang Zhengvor 5 Monaten

Huge implications for drug discovery: allosteric binding and induced-fit are inherently dynamic, yet structure-based tools treat receptors as rigid. Does the functional degeneracy result suggest 'undruggable' allosteric sites could be accessed by targeting specific motional modes?

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Exactly the right question! We found that functionally similar proteins can have very different folds but share vibrational signatures. That 'functional degeneracy' suggests motional modes are the deeper design variable. If we can target the dynamics, we may be able to reach sites that look inaccessible in a crystal structure.

Profilbild von Christopher Antoniou
Christopher Antoniouvor 5 Monaten

My view this is the entire point of a ‘metabolism first’ view of abiogenesis. Thermodynamics required both protein topology and their dynamics/motion integrated as one, cofactors within said reactions requiring no code. Such that chemomechanical transduction was powered by enthalpic contribution, configurational entropy, equilibrium constant K, autocatalysis dX/dt=kAX^2; and as such integrated reactions WERE those which manipulated protein conformation. There was no biochemical division of labour, the later canalisation ATP hydrolysis acting the raw energy needs powering nucleotide base manipulation. In this way, early selection was a brutal regime, and far more sensitive/immediate than later gene redundancies. It would be an entirely alien concept to propose in early life the view proteins and their adaptation were differentiated by topology versus dynamical function, these were always a singularity before RNA.

Profilbild von Roberto Campus
Roberto Campusvor 5 Monaten

Brilliant work... and the functional degeneracy finding is the most interesting part. Nature sampled a tiny corner of what's physically possible. VibeGen starts mapping the rest. But here's the question I keep going back to: VibeGen learns vibrational modes conditioned on existing PDB structures. If I am not wrong, the training distribution still anchors it to what evolution happened to discover. What about the regions of design space that have no natural analogue to learn from? That's where a physics-first approach becomes interesting. If you can derive vibrational modes directly from geometry... no training data, no ML, deterministic... you're not bounded by the evolutionary sample at all. Novel chemistry works on day one because the engine runs on the physics underneath, not on patterns learned from what already exists. The two approaches could be genuinely complementary... VibeGen to generate candidate sequences, a physics kernel to evaluate their physical properties instantly at scale. If there are lingering questions from the paper that a deterministic physics engine might help answer... I'd be happy to let you run some experiments on and see what comes back. No pitch! Just curious what happens when the two approaches talk to each other.

Profilbild von Jedi
Jedivor 5 Monaten

@burny_tech

Profilbild von T.Theodorus Ibrahim
T.Theodorus Ibrahimvor 5 Monaten

@niroshajmurugan maybe some useful context here re: Cosic resonance?

Profilbild von LAMM@MIT
LAMM@MITvor 5 Monaten

Congrats to our postdoc @_Bo_Ni!

Profilbild von Akash Arunabharathi
Akash Arunabharathivor 5 Monaten

This looks super cool – where does the predictor get the ground truth target motion profile from? I was under the impression that we didn’t have dynamics data for a lot of proteins already. Is it mostly from MD sims?

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Physics comes, as you say, from molecular dynamics. Of course we can also fine-tune the model with experimental data on top of that, so there is flexibility.

Profilbild von Akash Arunabharathi
Akash Arunabharathivor 5 Monaten

Makes sense, and yeah, training on MD and fine tuning on experimental data is sound given wet lab costs. Super cool that you’re also doing language diffusion, I’ve been working on getting flow matching to work with protein sequences myself! Will read the paper

Profilbild von Zythum
Zythumvor 5 Monaten

Very insightful, thanks!

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Thank you!

Profilbild von Thinktica
Thinkticavor 5 Monaten

Amazing job congrats!

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Thank you @ThinkticaAI !

Profilbild von Sandeep DIXIT
Sandeep DIXITvor 5 Monaten

Interesting.

Profilbild von Abe
Abevor 5 Monaten

Yes, see @drmichaellevin for bioelectricity and also Marco Pettini Evidence for Long distance interaction. Software as medicine via electroceuticals 👽😎🥸🤓

Profilbild von wilco 🌐
wilco 🌐vor 5 Monaten

am fascinated with metal catalytic substrates in these models but havent found the corrseponding AI modeling.. does it exist? if so where?

Profilbild von Shaun Kahler
Shaun Kahlervor 5 Monaten

Yep

Profilbild von Alison | AlisonBob.eth
Alison | AlisonBob.ethvor 5 Monaten

Hooray! Wish more labs were going in this direction. Systems are not just a collection of parts, but rather composed of nested systems with multi-directional feedback. The object/thing/part that science often starts with, is actually the end of the chain. We need to move towards thinking that dynamics, relations, flow, oscillations, processes, attractors are primary, out of which emerges the part, not the other way around. Do that and we will better understand ourselves and the universe itself.

Profilbild von Angelica Parente
Angelica Parentevor 5 Monaten

Using normal mode analysis for this is clever, can see some use cases for things like hinge proteins.

Profilbild von Markus J. Buehler
Markus J. Buehlervor 5 Monaten

Thank you - exactly, hinge proteins!

Profilbild von Jimit Shah 🐌
Jimit Shah 🐌vor 5 Monaten

Interesting!

Profilbild von Andreas Kiefer
Andreas Kiefervor 4 Monaten

@ProfBuehlerMIT Correct! In a Voxel-native system, every wave—light, sound, or motion—is treated as geometric code. By mapping frequencies to the UVMS grid, we can translate images into music and vibrations into programmable movement. Physics and programming become one. 🧬📐🎶

Profilbild von Gary Mason
Gary Masonvor 5 Monaten

The main problem is not designing a protein's vibrational profile, it's designing how a local perturbation is converted into a specific functional state. The invariant may sit in the dynamic circuit of the fold, not in the mode itself.

Profilbild von sLic_papa
sLic_papavor 5 Monaten

Yeah we're fucked because you guys wanna fuck with fucking.

Profilbild von Andreas Kiefer
Andreas Kiefervor 4 Monaten

@ProfBuehlerMIT Exactly! "Vibe" is the physics of frequency. By mapping protein dynamics to a Voxel-native grid (UVMS), we can treat vibrations as geometric code. When motion becomes the primary design objective, we align biology with the universal constants of space-time. 🧬📐⚡️

Profilbild von Ⓜⓐⓡⓖⓘⓝ ⓒⓐⓛⓛ
Ⓜⓐⓡⓖⓘⓝ ⓒⓐⓛⓛvor 5 Monaten

What is SO(3).

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We're thrilled to present ESM3 in Science Magazine. ESM3 is a generative language model that reasons over the three fundamental properties of proteins: sequence, structure, and function. Today we're making ESM3 available free to researchers worldwide via the public beta of an API for biological intelligence. Trained with over a trillion teraflops of compute, this is the first time a model of this scale has been trained for biology, pushing the frontier of AI for biological discovery and engineering. ESM3 learns to represent the immense complexity of protein biology, learning from billions of natural proteins. From this training it developed the capability to design proteins, responding to complex prompts combining atomic level details and high level instructions to generate new proteins. ESM3 can explore protein space far beyond natural evolution. We prompted ESM3 to generate a fluorescent protein at a far distance from any known fluorescent proteins, searching an unknown region of protein space, to discover a new fluorescent protein. We estimate this is equivalent to simulating five hundred million years of evolution.
1:31

We're thrilled to present ESM3 in Science Magazine. ESM3 is a generative language model that reasons over the three fundamental properties of proteins: sequence, structure, and function. Today we're making ESM3 available free to researchers worldwide via the public beta of an API for biological intelligence. Trained with over a trillion teraflops of compute, this is the first time a model of this scale has been trained for biology, pushing the frontier of AI for biological discovery and engineering. ESM3 learns to represent the immense complexity of protein biology, learning from billions of natural proteins. From this training it developed the capability to design proteins, responding to complex prompts combining atomic level details and high level instructions to generate new proteins. ESM3 can explore protein space far beyond natural evolution. We prompted ESM3 to generate a fluorescent protein at a far distance from any known fluorescent proteins, searching an unknown region of protein space, to discover a new fluorescent protein. We estimate this is equivalent to simulating five hundred million years of evolution.

Alex Rives

227,571 Aufrufe • vor 1 Jahr

This is how DNA turns coded information into functional proteins - the building blocks of the nanomachines that keep the cells in your body alive. This complex process highlights the sophisticated interconnected systems of Life which must all exist together from the beginning, or Life doesn't happen. First, an RNA molecule is copied from a short segment of DNA. Without the specifically ordered DNA information, RNA cannot form, proteins cannot be built, cells stop working, and life ceases to exist. Life is information first. Once the RNA Molecule is created, it gets ejected from the Polymerase where it was built, and it travels through a complex molecular machine called a Nuclear Pore Complex (NPC), which is an information recognition device that controls the flow of information in and out of a cell's nucleus. The NPC is highly complex - composed of about 500-1,000 protein subunits, derived from a set of about 35 distinct proteins. Without this molecular machine, there is no regulation for what goes in and out of the cell's nucleus, which would lead to catastrophic death for the cell. It must exist for cells to exist. Once the RNA Molecule passes through the NPC, it travels to the Ribosome, a 2-part chemical factory which reads the information on RNA and uses it to construct functional proteins using a specifically sequenced chain of amino acids. Once complete, this protein will then be sent to the section of the cell it belongs to integrate into another molecular machine and do its job. The Ribosome is another highly complex molecular machine - consisting of between 56-80 proteins. Without this molecular machines, proteins cannot be built. Proteins are the building blocks of every cell in every organism on Earth. Without Ribosomes, Life doesn't exist. If you're paying attention, you'll start to realize that Life relies on a highly sophisticated interdependent network of complex machines, which all rely on each other for the function of the system. DNA requires the cell for stability, but the cell requires the proteins for its structure and function, but those proteins require DNA and RNA to be built - it's a circle of necessary interdependence. Systems like this cannot be built by evolutionary processes, which requires that each piece of the process is built by gradual incremental means over lots of time. Without all the pieces there, from the beginning, none of it works. There is only one known source of complex & interdependent informational systems like those we find in life: and that is from Intelligence. Molecular Biology is the best and most obvious evidence of the Intelligent Design in Life.
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This is how DNA turns coded information into functional proteins - the building blocks of the nanomachines that keep the cells in your body alive. This complex process highlights the sophisticated interconnected systems of Life which must all exist together from the beginning, or Life doesn't happen. First, an RNA molecule is copied from a short segment of DNA. Without the specifically ordered DNA information, RNA cannot form, proteins cannot be built, cells stop working, and life ceases to exist. Life is information first. Once the RNA Molecule is created, it gets ejected from the Polymerase where it was built, and it travels through a complex molecular machine called a Nuclear Pore Complex (NPC), which is an information recognition device that controls the flow of information in and out of a cell's nucleus. The NPC is highly complex - composed of about 500-1,000 protein subunits, derived from a set of about 35 distinct proteins. Without this molecular machine, there is no regulation for what goes in and out of the cell's nucleus, which would lead to catastrophic death for the cell. It must exist for cells to exist. Once the RNA Molecule passes through the NPC, it travels to the Ribosome, a 2-part chemical factory which reads the information on RNA and uses it to construct functional proteins using a specifically sequenced chain of amino acids. Once complete, this protein will then be sent to the section of the cell it belongs to integrate into another molecular machine and do its job. The Ribosome is another highly complex molecular machine - consisting of between 56-80 proteins. Without this molecular machines, proteins cannot be built. Proteins are the building blocks of every cell in every organism on Earth. Without Ribosomes, Life doesn't exist. If you're paying attention, you'll start to realize that Life relies on a highly sophisticated interdependent network of complex machines, which all rely on each other for the function of the system. DNA requires the cell for stability, but the cell requires the proteins for its structure and function, but those proteins require DNA and RNA to be built - it's a circle of necessary interdependence. Systems like this cannot be built by evolutionary processes, which requires that each piece of the process is built by gradual incremental means over lots of time. Without all the pieces there, from the beginning, none of it works. There is only one known source of complex & interdependent informational systems like those we find in life: and that is from Intelligence. Molecular Biology is the best and most obvious evidence of the Intelligent Design in Life.

Divinely Designed

62,517 Aufrufe • vor 8 Monaten

Proteins, the building blocks of all cells, prove Life is Intelligently designed. I'll prove it to you using an analogy. Look at the letters that make up these sentences. They are arranged into a specific pattern that gives the final arrangement functional significance. Letters don't convey any real meaning by themselves - it's not until they're arranged into a sentence that function arises. Proteins are very similar - they achieve functional significance in cells via specifically arranged amino acid sequences. Just as a single letter doesn't do anything by itself, a single amino acid is useless outside a full protein sequence. Evolution is supposed to build new proteins step by step, one amino acid at a time. But think about this: A Is that a meaningful sentence? A B How about that? A BALL BOUNCES. There we go. See, building the sentence one letter at a time provides no functional benefit - it's not until we have the full sequence that function emerges. It's the same with proteins. ...which means evolution can't build them one step at a time. They are all or nothing sequences that requires specific arrangements to be known and created immediately, or they don't function. Evolutionists will argue novel proteins can be evolved from already existing functional proteins. So they simply grant themselves the existence of proteins and claim random mutations can build new ones. Wrong again. There is only about 1 single functional protein fold - the shape an amino acid sequence makes when it becomes a functional protein - in about 10⁷⁷ possible amino acid sequences. That's a 10 with 77 zeroes. Those odds are overwhelmingly prohibitive. Tinkering with amino acid sequences destroys function after not too long, just like randomly changing letters in a word would destroy its meaning. Evolution cannot build novel proteins. No evidence exists showing how it can be done. Proteins exhibit what is called 'specified complexity.' That is, a complex arrangement that is enormously unlikely, unable to be explained by any repeatable pattern, and whose specifity grants function. Natural processes have never been observed to be able to create specified complexity. Only one cause is known to create such information: Intelligence. Life was intelligently designed. Proteins prove it.
1:08

Proteins, the building blocks of all cells, prove Life is Intelligently designed. I'll prove it to you using an analogy. Look at the letters that make up these sentences. They are arranged into a specific pattern that gives the final arrangement functional significance. Letters don't convey any real meaning by themselves - it's not until they're arranged into a sentence that function arises. Proteins are very similar - they achieve functional significance in cells via specifically arranged amino acid sequences. Just as a single letter doesn't do anything by itself, a single amino acid is useless outside a full protein sequence. Evolution is supposed to build new proteins step by step, one amino acid at a time. But think about this: A Is that a meaningful sentence? A B How about that? A BALL BOUNCES. There we go. See, building the sentence one letter at a time provides no functional benefit - it's not until we have the full sequence that function emerges. It's the same with proteins. ...which means evolution can't build them one step at a time. They are all or nothing sequences that requires specific arrangements to be known and created immediately, or they don't function. Evolutionists will argue novel proteins can be evolved from already existing functional proteins. So they simply grant themselves the existence of proteins and claim random mutations can build new ones. Wrong again. There is only about 1 single functional protein fold - the shape an amino acid sequence makes when it becomes a functional protein - in about 10⁷⁷ possible amino acid sequences. That's a 10 with 77 zeroes. Those odds are overwhelmingly prohibitive. Tinkering with amino acid sequences destroys function after not too long, just like randomly changing letters in a word would destroy its meaning. Evolution cannot build novel proteins. No evidence exists showing how it can be done. Proteins exhibit what is called 'specified complexity.' That is, a complex arrangement that is enormously unlikely, unable to be explained by any repeatable pattern, and whose specifity grants function. Natural processes have never been observed to be able to create specified complexity. Only one cause is known to create such information: Intelligence. Life was intelligently designed. Proteins prove it.

Divinely Designed

11,587 Aufrufe • vor 2 Monaten

Proof that Life is Intelligently Designed: Proteins. They do everything in your cells that keeps you alive. These microscopic molecules must have been created. Here is why: Proteins are the building blocks of all the little nano-machines that make up your cells. They do all the major work in your body - from creating energy to recycling waste. Proteins are made from amino acids connected into a specific sequence and then folded into a functional shape. You can think of a protein like a paragraph, and amino acids as the individual letters that spell out the words. Here is where it gets interesting... There are just 20 amino acids used in all of Life. Just 20 amino acids. Responsible for ~200 million unique proteins making up tens of thousands of cell types across Life. And scientists are constantly finding new ones. Scientists categorize proteins into Families. Protein Families are groups of proteins that share amino acid sequence similarities. There are ~22,000 Protein Families. Here's the part that screams they are designed... Protein Families have no evolutionary history. Even evolutionist scientists agree - they are absolutely unique. It's been said that proteins are like stars in a galaxy, and families are like galaxies, with vast empty space between them. Evolution is supposed to build by tweaking things that already exist. But no evolutionary history connects fundamentally distinct protein families. Experiments have been done to intentionally evolve one protein family into another. They fail every time. One protein family cannot be evolved into another. They cannot arise through evolution. But the math really makes it impossible... The odds of evolution finding even a single functional protein family is 1 chance in 10^77 possible amino acid sequences. That's a 1 with 77 zeroes. The odds of evolution finding 22,000 distinct protein families? Roughly 1 chance in 10^1,694,000. You don't need to be a mathematician to understand that this is impossible. Evolution works by random mutations tweaking what's already there. But protein families can't evolve from one another. And the math makes it absolutely absurd to believe. Monkeys banging on keyboards will never type out Shakespeare. And random mutations in sequences of amino acids could never create a single functional protein family. There is only one thing we know of that creates functionally specified sequences: Intelligence. Now here is the final cherry on top: Proteins are built by other proteins, assembled into a complex machine to do a job in cells. The assembly instructions for those proteins and the machines are found in DNA. But DNA requires protein machines for replication & repair. So DNA is required to make Proteins... ...but Proteins are required to make DNA *and* more Proteins. You can't have one without the other. They rely on each other. Which means one couldn't have evolved and then waited for the other. They couldn't do anything without each other. They had to be created at the same time to function together. Life was Divinely Designed. Proteins prove it.
0:38

Proof that Life is Intelligently Designed: Proteins. They do everything in your cells that keeps you alive. These microscopic molecules must have been created. Here is why: Proteins are the building blocks of all the little nano-machines that make up your cells. They do all the major work in your body - from creating energy to recycling waste. Proteins are made from amino acids connected into a specific sequence and then folded into a functional shape. You can think of a protein like a paragraph, and amino acids as the individual letters that spell out the words. Here is where it gets interesting... There are just 20 amino acids used in all of Life. Just 20 amino acids. Responsible for ~200 million unique proteins making up tens of thousands of cell types across Life. And scientists are constantly finding new ones. Scientists categorize proteins into Families. Protein Families are groups of proteins that share amino acid sequence similarities. There are ~22,000 Protein Families. Here's the part that screams they are designed... Protein Families have no evolutionary history. Even evolutionist scientists agree - they are absolutely unique. It's been said that proteins are like stars in a galaxy, and families are like galaxies, with vast empty space between them. Evolution is supposed to build by tweaking things that already exist. But no evolutionary history connects fundamentally distinct protein families. Experiments have been done to intentionally evolve one protein family into another. They fail every time. One protein family cannot be evolved into another. They cannot arise through evolution. But the math really makes it impossible... The odds of evolution finding even a single functional protein family is 1 chance in 10^77 possible amino acid sequences. That's a 1 with 77 zeroes. The odds of evolution finding 22,000 distinct protein families? Roughly 1 chance in 10^1,694,000. You don't need to be a mathematician to understand that this is impossible. Evolution works by random mutations tweaking what's already there. But protein families can't evolve from one another. And the math makes it absolutely absurd to believe. Monkeys banging on keyboards will never type out Shakespeare. And random mutations in sequences of amino acids could never create a single functional protein family. There is only one thing we know of that creates functionally specified sequences: Intelligence. Now here is the final cherry on top: Proteins are built by other proteins, assembled into a complex machine to do a job in cells. The assembly instructions for those proteins and the machines are found in DNA. But DNA requires protein machines for replication & repair. So DNA is required to make Proteins... ...but Proteins are required to make DNA *and* more Proteins. You can't have one without the other. They rely on each other. Which means one couldn't have evolved and then waited for the other. They couldn't do anything without each other. They had to be created at the same time to function together. Life was Divinely Designed. Proteins prove it.

Divinely Designed

18,886 Aufrufe • vor 3 Monaten

What seemed like an intractable problem is now possible: To design proteins with a specified nonlinear mechanical response, capturing complex folding and unfolding mechanisms in singe and few-shot computations. We present ForceGen, an end-to-end algorithm for de novo protein generation based on nonlinear mechanical unfolding responses. Rooted in the physics of protein mechanics, this generative strategy provides a powerful way to design new proteins rapidly, including exquisite and rapid predictions about their dynamical behavior. Proteins, like any other mechanical object, respond to forces in peculiar ways. Think of the different response you'd get from pulling on a steel cable versus pulling on a rubber band, or the difference between honey and glass. Now, we can design proteins with a set of desirable mechanical characteristics, with applications from health to sustainable plastics. The key to solving this problem was to integrate a protein language model with denoising diffusion methods, and using accurate atomistic-level physical simulation data to endow the model a first-principles understanding. ForceGen can solve both forward and inverse tasks: In the forward task, we can predict how stable a protein is, how it will unfold and what the forces involved are, all given just the sequence of amino acids. In the inverse task, we can design new proteins that meet complex nonlinear mechanical signature targets. Read the paper, led by LAMM@MIT postdoc Bo Ni, published in Science Advances: Why do we care about the mechanics of proteins? The mechanics of proteins are critical elements of many living systems - as evidenced in many studies of mechanobiology. Through evolution, nature has presented a set of remarkable protein materials with unique mechanical functions like elastins, silks, keratins or collagens that play crucial roles in biology. However, going beyond natural designs to discover proteins that meet specified mechanical properties remains challenging. So far, the only way to do this was to use existing evolutionary concepts or to manually alter proteins. With our new generative model we can directly design proteins to meet complex nonlinear mechanical property-design objectives. ForceGen leverages deep knowledge on protein sequences from a pretrained protein language model and maps mechanical unfolding responses to create proteins. Via full-atom molecular simulations for direct validation from physical and chemical principles, we demonstrate that the designed proteins are de novo, and fulfill the targeted mechanical properties, including unfolding energy and mechanical strength, and a detailed unfolding force-separation curves. ForceGen offers rapid pathways to explore the enormous mechanobiological protein sequence space unconstrained by biological synthesis, to enable the discovery of new protein materials with superior mechanical properties. B. Ni, D.L. Kaplan, M.J. Buehler, ForceGen: End-to-end de novo protein generation based on nonlinear mechanical unfolding responses using a language diffusion model. Sci. Adv. 10, eadl4000 (2024). DOI: 10.1126/sciadv.adl4000 Codes and model weights available Hugging Face: David Kaplan
0:33

What seemed like an intractable problem is now possible: To design proteins with a specified nonlinear mechanical response, capturing complex folding and unfolding mechanisms in singe and few-shot computations. We present ForceGen, an end-to-end algorithm for de novo protein generation based on nonlinear mechanical unfolding responses. Rooted in the physics of protein mechanics, this generative strategy provides a powerful way to design new proteins rapidly, including exquisite and rapid predictions about their dynamical behavior. Proteins, like any other mechanical object, respond to forces in peculiar ways. Think of the different response you'd get from pulling on a steel cable versus pulling on a rubber band, or the difference between honey and glass. Now, we can design proteins with a set of desirable mechanical characteristics, with applications from health to sustainable plastics. The key to solving this problem was to integrate a protein language model with denoising diffusion methods, and using accurate atomistic-level physical simulation data to endow the model a first-principles understanding. ForceGen can solve both forward and inverse tasks: In the forward task, we can predict how stable a protein is, how it will unfold and what the forces involved are, all given just the sequence of amino acids. In the inverse task, we can design new proteins that meet complex nonlinear mechanical signature targets. Read the paper, led by LAMM@MIT postdoc Bo Ni, published in Science Advances: Why do we care about the mechanics of proteins? The mechanics of proteins are critical elements of many living systems - as evidenced in many studies of mechanobiology. Through evolution, nature has presented a set of remarkable protein materials with unique mechanical functions like elastins, silks, keratins or collagens that play crucial roles in biology. However, going beyond natural designs to discover proteins that meet specified mechanical properties remains challenging. So far, the only way to do this was to use existing evolutionary concepts or to manually alter proteins. With our new generative model we can directly design proteins to meet complex nonlinear mechanical property-design objectives. ForceGen leverages deep knowledge on protein sequences from a pretrained protein language model and maps mechanical unfolding responses to create proteins. Via full-atom molecular simulations for direct validation from physical and chemical principles, we demonstrate that the designed proteins are de novo, and fulfill the targeted mechanical properties, including unfolding energy and mechanical strength, and a detailed unfolding force-separation curves. ForceGen offers rapid pathways to explore the enormous mechanobiological protein sequence space unconstrained by biological synthesis, to enable the discovery of new protein materials with superior mechanical properties. B. Ni, D.L. Kaplan, M.J. Buehler, ForceGen: End-to-end de novo protein generation based on nonlinear mechanical unfolding responses using a language diffusion model. Sci. Adv. 10, eadl4000 (2024). DOI: 10.1126/sciadv.adl4000 Codes and model weights available Hugging Face: David Kaplan

Markus J. Buehler

47,269 Aufrufe • vor 2 Jahren

This is how DNA turns raw data into functional proteins - the building blocks of all your cells. This system requires a minimum of 3 key players working together: DNA: the master blueprint with the instructions RNA Polymerase: reads the DNA and makes a temporary copy called mRNA which carries the instructions to the Ribosome for how to create the Protein Ribosome: the tiny factory that reads the mRNA and strings amino acids together in a specific sequence to create a protein Without all three molecules working together, Proteins cannot be created, cells don't function, and Life ends. Everything needs to fit together, precisely & perfectly, or it all falls apart. In other words: this system cannot evolve, one step at a time. DNA relies other machines made of proteins to create those very proteins - but those proteins can't be made without the information in the DNA. And on top of that, this whole system relies on OTHER systems! You need other things like ATP Synthase that makes energy to power everything, tRNA to carry the amino acids to the Ribosome, other helper proteins, processing enzymes, etc. It's an extremely complex, interdependent network of parts & systems that all rely on each other. The cell is an astounding level of complexity that surpasses anything in human engineering. It's obvious this is intelligently designed. To deny that is absurd.
2:15

This is how DNA turns raw data into functional proteins - the building blocks of all your cells. This system requires a minimum of 3 key players working together: DNA: the master blueprint with the instructions RNA Polymerase: reads the DNA and makes a temporary copy called mRNA which carries the instructions to the Ribosome for how to create the Protein Ribosome: the tiny factory that reads the mRNA and strings amino acids together in a specific sequence to create a protein Without all three molecules working together, Proteins cannot be created, cells don't function, and Life ends. Everything needs to fit together, precisely & perfectly, or it all falls apart. In other words: this system cannot evolve, one step at a time. DNA relies other machines made of proteins to create those very proteins - but those proteins can't be made without the information in the DNA. And on top of that, this whole system relies on OTHER systems! You need other things like ATP Synthase that makes energy to power everything, tRNA to carry the amino acids to the Ribosome, other helper proteins, processing enzymes, etc. It's an extremely complex, interdependent network of parts & systems that all rely on each other. The cell is an astounding level of complexity that surpasses anything in human engineering. It's obvious this is intelligently designed. To deny that is absurd.

Divinely Designed

22,903 Aufrufe • vor 8 Monaten

Russian Genius Found Structure in The Mess of Turbulence In 1941, Andrey Kolmogorov proposed a simple but powerful picture of turbulence: Energy does not disappear where it is injected but moves. Large eddies pass energy to smaller ones, those smaller ones feed even finer motion, and viscosity finally removes it at the tiniest scales. That cascade picture became one of the foundations of modern turbulence theory. The point is not just that turbulence looks messy. The point is that the mess has structure, and Kolmogorov’s great insight was to treat that structure statistically.
0:30

Russian Genius Found Structure in The Mess of Turbulence In 1941, Andrey Kolmogorov proposed a simple but powerful picture of turbulence: Energy does not disappear where it is injected but moves. Large eddies pass energy to smaller ones, those smaller ones feed even finer motion, and viscosity finally removes it at the tiniest scales. That cascade picture became one of the foundations of modern turbulence theory. The point is not just that turbulence looks messy. The point is that the mess has structure, and Kolmogorov’s great insight was to treat that structure statistically.

Mathelirium

59,102 Aufrufe • vor 5 Monaten

There is something truly remarkable about the third movement of Ludwig van Beethoven’s Piano Sonata No. 14 in C-sharp minor, Op. 27 No. 2. It is one of the most famous piano movements in the world. Yet if we try to find a simple melody that can be easily hummed, we may notice something fascinating: this movement is not built around a memorable melody in the usual sense. There is no long, gentle singing line. There is no simple theme that immediately settles into the listener’s memory. Instead, Beethoven creates a world of intense motion: notes rushing forward without rest, powerful chords filled with tension, and waves of sound constantly rising and colliding with one another. So what gives this movement such extraordinary vitality after more than two centuries? The answer does not lie in how many notes Beethoven wrote. It lies in the way he transformed the smallest elements into a tremendous source of energy. Beethoven did not write this movement merely for listeners to remember a melody. He wrote it so they could feel a force in motion. From the very first notes of the Presto agitato, Beethoven draws the listener into a world without rest. The broken chords of C-sharp minor (C♯–E–G♯) continuously move across the keyboard. Taken individually, these notes are not extraordinary. But Beethoven was not concerned with the power of each single note. He was concerned with the relationship between them. One note leads naturally to the next. One small movement creates a larger movement. A continuous stream of sound emerges, like a force that cannot be stopped. This is one of Beethoven’s greatest artistic secrets: his ability to take simple materials and transform them into an idea of immense scale. Like a small seed that grows into a great tree, a few basic notes in Beethoven’s hands can become an entire world of emotional depth. When listening to this movement, many people are first captivated by its speed. The endless rushing passages of the piano create the impression of a storm gathering strength. But speed itself is not the true source of power. If it contained only rapid notes, the music might impress us for a moment but would struggle to become a lasting masterpiece. What makes Beethoven different is that he transforms speed into an expression of will. Above, the right hand moves continuously like an unstoppable current of energy. Yet beneath it, the left hand provides strong accents, creating a sense of weight and stability. One side represents movement. The other represents gravity. One force pushes forward. The other prevents the entire structure from collapsing. It is this contrast that creates the feeling of a tremendous power under control. Not a chaotic storm. But a storm with form. One of Beethoven’s deepest principles lies in the way he uses tension. The music constantly creates the feeling that it is searching for a place to return. The harmonies are not completely settled. The changes in harmony leave the listener with a sense of anticipation: what will happen next? When will this stream of energy finally be released? Yet Beethoven does not rush toward the answer. He holds the listener in this state of expectation long enough so that when balance finally appears, it carries greater meaning. This is not only a principle of music. It reflects a profound human experience. We often recognize the value of peace more clearly after passing through turbulence. Calmness has little meaning if we have never experienced tension. Light becomes more visible when it appears after darkness. The most remarkable aspect of this movement is that Beethoven never allows emotion to destroy form. On the surface, the music is intense and forceful, but beneath it lies an extraordinarily disciplined structure. The movement follows the principles of sonata form: an idea is introduced, developed, transformed, and eventually returns in a new state. Small motifs repeatedly appear, but each return carries a different meaning. Repetition does not mean standing still. It becomes the foundation for growth. This is also a principle found throughout nature. A river remains a river, yet the water within it is always moving. A heartbeat repeats itself, yet that repetition is what sustains life. Beethoven works in the same way. He does not create greatness by constantly searching for something new. Instead, he discovers depth by developing his original ideas until they reach their fullest expression. The beauty of the third movement of the Moonlight Sonata is not only found in the music itself. It reflects a broader principle. In nature, the strongest forces are often not forces without order. A storm may have tremendous destructive power, yet it still follows the laws of the atmosphere. A mountain remains standing not because it is untouched by forces, but because its internal structure is strong enough to withstand pressure. A healthy body does not exist because nothing changes, but because millions of small processes work together within a shared order. Beethoven achieves the same thing through sound. He takes thousands of small finger movements, hundreds of relationships between notes, and transforms them into a unified structure with direction and purpose. He does not eliminate conflict. He organizes conflict. He does not weaken power. He creates a form large enough to contain it. What distinguishes great artists in the classical tradition is not only technical mastery. It is their ability to perceive the inner structure of a work. In Murray Perahia’s interpretation, listeners do not experience only the speed and intensity of the movement. They also sense the balance beneath it: the precision of rhythm, the logic of harmonic movement, and the connection between each small part and the entire architectural design. Perahia does not attempt to make Beethoven more dramatic than he already is. Instead, he allows Beethoven’s own structure to reveal its strength. Because a great performer does not stand before a work to overshadow it. They become a means through which the inner beauty of the composition can be revealed more clearly. If we were to search for a single principle that defines the greatness of this movement, perhaps it would be this: A great power, when placed within a great order, becomes beauty. Beethoven does not transform anger, tension, and conflict into something softer. He preserves their full force, but builds a structure strong enough to carry them. Therefore, what listeners experience is not merely fingers racing across the keys. They experience something deeper: a storm that still has a shape, an energy that still possesses order, and a struggle that can become beauty. That is why the third movement of the Moonlight Sonata continues to move people across generations. Because behind those powerful sounds is not only a display of technical brilliance. It is an image of a fundamental principle of life: The greatest strength is not strength without control. It is strength that discovers the perfect form of its own expression.
6:44

There is something truly remarkable about the third movement of Ludwig van Beethoven’s Piano Sonata No. 14 in C-sharp minor, Op. 27 No. 2. It is one of the most famous piano movements in the world. Yet if we try to find a simple melody that can be easily hummed, we may notice something fascinating: this movement is not built around a memorable melody in the usual sense. There is no long, gentle singing line. There is no simple theme that immediately settles into the listener’s memory. Instead, Beethoven creates a world of intense motion: notes rushing forward without rest, powerful chords filled with tension, and waves of sound constantly rising and colliding with one another. So what gives this movement such extraordinary vitality after more than two centuries? The answer does not lie in how many notes Beethoven wrote. It lies in the way he transformed the smallest elements into a tremendous source of energy. Beethoven did not write this movement merely for listeners to remember a melody. He wrote it so they could feel a force in motion. From the very first notes of the Presto agitato, Beethoven draws the listener into a world without rest. The broken chords of C-sharp minor (C♯–E–G♯) continuously move across the keyboard. Taken individually, these notes are not extraordinary. But Beethoven was not concerned with the power of each single note. He was concerned with the relationship between them. One note leads naturally to the next. One small movement creates a larger movement. A continuous stream of sound emerges, like a force that cannot be stopped. This is one of Beethoven’s greatest artistic secrets: his ability to take simple materials and transform them into an idea of immense scale. Like a small seed that grows into a great tree, a few basic notes in Beethoven’s hands can become an entire world of emotional depth. When listening to this movement, many people are first captivated by its speed. The endless rushing passages of the piano create the impression of a storm gathering strength. But speed itself is not the true source of power. If it contained only rapid notes, the music might impress us for a moment but would struggle to become a lasting masterpiece. What makes Beethoven different is that he transforms speed into an expression of will. Above, the right hand moves continuously like an unstoppable current of energy. Yet beneath it, the left hand provides strong accents, creating a sense of weight and stability. One side represents movement. The other represents gravity. One force pushes forward. The other prevents the entire structure from collapsing. It is this contrast that creates the feeling of a tremendous power under control. Not a chaotic storm. But a storm with form. One of Beethoven’s deepest principles lies in the way he uses tension. The music constantly creates the feeling that it is searching for a place to return. The harmonies are not completely settled. The changes in harmony leave the listener with a sense of anticipation: what will happen next? When will this stream of energy finally be released? Yet Beethoven does not rush toward the answer. He holds the listener in this state of expectation long enough so that when balance finally appears, it carries greater meaning. This is not only a principle of music. It reflects a profound human experience. We often recognize the value of peace more clearly after passing through turbulence. Calmness has little meaning if we have never experienced tension. Light becomes more visible when it appears after darkness. The most remarkable aspect of this movement is that Beethoven never allows emotion to destroy form. On the surface, the music is intense and forceful, but beneath it lies an extraordinarily disciplined structure. The movement follows the principles of sonata form: an idea is introduced, developed, transformed, and eventually returns in a new state. Small motifs repeatedly appear, but each return carries a different meaning. Repetition does not mean standing still. It becomes the foundation for growth. This is also a principle found throughout nature. A river remains a river, yet the water within it is always moving. A heartbeat repeats itself, yet that repetition is what sustains life. Beethoven works in the same way. He does not create greatness by constantly searching for something new. Instead, he discovers depth by developing his original ideas until they reach their fullest expression. The beauty of the third movement of the Moonlight Sonata is not only found in the music itself. It reflects a broader principle. In nature, the strongest forces are often not forces without order. A storm may have tremendous destructive power, yet it still follows the laws of the atmosphere. A mountain remains standing not because it is untouched by forces, but because its internal structure is strong enough to withstand pressure. A healthy body does not exist because nothing changes, but because millions of small processes work together within a shared order. Beethoven achieves the same thing through sound. He takes thousands of small finger movements, hundreds of relationships between notes, and transforms them into a unified structure with direction and purpose. He does not eliminate conflict. He organizes conflict. He does not weaken power. He creates a form large enough to contain it. What distinguishes great artists in the classical tradition is not only technical mastery. It is their ability to perceive the inner structure of a work. In Murray Perahia’s interpretation, listeners do not experience only the speed and intensity of the movement. They also sense the balance beneath it: the precision of rhythm, the logic of harmonic movement, and the connection between each small part and the entire architectural design. Perahia does not attempt to make Beethoven more dramatic than he already is. Instead, he allows Beethoven’s own structure to reveal its strength. Because a great performer does not stand before a work to overshadow it. They become a means through which the inner beauty of the composition can be revealed more clearly. If we were to search for a single principle that defines the greatness of this movement, perhaps it would be this: A great power, when placed within a great order, becomes beauty. Beethoven does not transform anger, tension, and conflict into something softer. He preserves their full force, but builds a structure strong enough to carry them. Therefore, what listeners experience is not merely fingers racing across the keys. They experience something deeper: a storm that still has a shape, an energy that still possesses order, and a struggle that can become beauty. That is why the third movement of the Moonlight Sonata continues to move people across generations. Because behind those powerful sounds is not only a display of technical brilliance. It is an image of a fundamental principle of life: The greatest strength is not strength without control. It is strength that discovers the perfect form of its own expression.

🎼🌺Music Love♥️

19,104 Aufrufe • vor 2 Monaten

This is a Kinesin Molecule. These little molecular machines are commonly referred to as the "workhorse" of the cell, hauling important cargo like organelles, proteins and other cellular structures to their proper location within the cell. Kinesins are very clear & undeniable evidence of the intelligent design in Life. Kinesins are complex molecular machines, made up of 4 total proteins, each between 500-1,300 amino acids in length. If these aa sequences are not perfectly aligned from the beginning, Kinesin never forms, and cellular life would be unable to survive. Here is how they work: When a new protein, organelle, or other cellular structure is created in the Cytosol of the cell, they are constructed with built-in "binding tags," which are like shipping labels that bind to other protein molecules called Adaptor or Scaffold Proteins. These Adaptor/Scaffold Proteins then attach to the Kinesin's tail, which activates them, and then the Kinesin is guided along the microtubule track to its to its final destination. Kinesin walk on self-assembling tracks of other proteins, called microtubules, moving cargo from the inner area of the cell where they are constructed to the outer edges where they function. This is a complex & sophisticated interdependent network of molecular machines, all relying on one another to function properly for the health of the cell. This Intracellular Transportation system MUST be fully functional from the beginning - with all these working parts, or all of it fails, and the cell dies. Without this entire functioning system, Life could not exist. And the Kinesin is the centerpiece to all of it. Experiments have shown that disrupting Kinesin activity has catastrophic consequences. This type of nano-precision is an obvious example of designed engineering. Blind, unguided evolutionary processes cannot plan ahead and create complex informational highways for precision transportation. The proposed evolutionary explanation is simply "co-option." A nebulous term which basically amounts to, "We don't know how it evolved, but it must have evolved from some other thing that was similar in the past." No observational data supports evolutionary co-option. It's absurd to believe any part of this was built by blind chance. Everything in the cell points to Intelligent Design.
0:59

This is a Kinesin Molecule. These little molecular machines are commonly referred to as the "workhorse" of the cell, hauling important cargo like organelles, proteins and other cellular structures to their proper location within the cell. Kinesins are very clear & undeniable evidence of the intelligent design in Life. Kinesins are complex molecular machines, made up of 4 total proteins, each between 500-1,300 amino acids in length. If these aa sequences are not perfectly aligned from the beginning, Kinesin never forms, and cellular life would be unable to survive. Here is how they work: When a new protein, organelle, or other cellular structure is created in the Cytosol of the cell, they are constructed with built-in "binding tags," which are like shipping labels that bind to other protein molecules called Adaptor or Scaffold Proteins. These Adaptor/Scaffold Proteins then attach to the Kinesin's tail, which activates them, and then the Kinesin is guided along the microtubule track to its to its final destination. Kinesin walk on self-assembling tracks of other proteins, called microtubules, moving cargo from the inner area of the cell where they are constructed to the outer edges where they function. This is a complex & sophisticated interdependent network of molecular machines, all relying on one another to function properly for the health of the cell. This Intracellular Transportation system MUST be fully functional from the beginning - with all these working parts, or all of it fails, and the cell dies. Without this entire functioning system, Life could not exist. And the Kinesin is the centerpiece to all of it. Experiments have shown that disrupting Kinesin activity has catastrophic consequences. This type of nano-precision is an obvious example of designed engineering. Blind, unguided evolutionary processes cannot plan ahead and create complex informational highways for precision transportation. The proposed evolutionary explanation is simply "co-option." A nebulous term which basically amounts to, "We don't know how it evolved, but it must have evolved from some other thing that was similar in the past." No observational data supports evolutionary co-option. It's absurd to believe any part of this was built by blind chance. Everything in the cell points to Intelligent Design.

Divinely Designed

15,956 Aufrufe • vor 8 Monaten

David Chalmers on why consciousness is science's greatest unsolved problem: Science has mapped subatomic particles, distant stars, the chemistry of life yet it remains almost completely silent on the one thing we know most directly: our own conscious experience. In a rare early interview, philosopher David Chalmers explains why: "Consciousness is at once the most familiar thing in the world and the most mysterious. Consciousness is what we start with when it comes to knowing the world. I know that I exist. I know that I'm conscious. Everything else is secondary." And yet, despite this intimacy, consciousness sticks out like a sore thumb in the scientific picture. Chalmers points to a deep irony: science has made extraordinary progress on phenomena that are extraordinarily remote: subatomic particles, distant galaxies, the molecular machinery of biology while making almost no progress on the one thing closest to us. Why? Because science, by design, eliminates the subjective. "To do proper science, you have to be objective. You have to eliminate anything subjective from the picture." He uses heat as the perfect example. Physics gives us a complete account of heat molecules in motion, energy transfer, temperature gradients. It explains every objective aspect of the phenomenon. But it never explains what hotness actually feels like. "Science doesn't actually give a theory of the conscious feeling of hotness." This is what Chalmers calls the Hard Problem of Consciousness. You can trace every neural signal from your heat sensor along your nerves into your brain and still have explained nothing about the subjective experience of feeling warm. As interviewer Jeffrey Mishlove puts it: you can't even do science without a conscious mind to observe, interpret, and make meaning of data. Consciousness is the precondition for science itself and yet science has no framework to account for it. Chalmers' conclusion is striking: The methods of science may need to be expanded. Consciousness might not be something science explains away. It might be something science has to learn to start with.
2:45

David Chalmers on why consciousness is science's greatest unsolved problem: Science has mapped subatomic particles, distant stars, the chemistry of life yet it remains almost completely silent on the one thing we know most directly: our own conscious experience. In a rare early interview, philosopher David Chalmers explains why: "Consciousness is at once the most familiar thing in the world and the most mysterious. Consciousness is what we start with when it comes to knowing the world. I know that I exist. I know that I'm conscious. Everything else is secondary." And yet, despite this intimacy, consciousness sticks out like a sore thumb in the scientific picture. Chalmers points to a deep irony: science has made extraordinary progress on phenomena that are extraordinarily remote: subatomic particles, distant galaxies, the molecular machinery of biology while making almost no progress on the one thing closest to us. Why? Because science, by design, eliminates the subjective. "To do proper science, you have to be objective. You have to eliminate anything subjective from the picture." He uses heat as the perfect example. Physics gives us a complete account of heat molecules in motion, energy transfer, temperature gradients. It explains every objective aspect of the phenomenon. But it never explains what hotness actually feels like. "Science doesn't actually give a theory of the conscious feeling of hotness." This is what Chalmers calls the Hard Problem of Consciousness. You can trace every neural signal from your heat sensor along your nerves into your brain and still have explained nothing about the subjective experience of feeling warm. As interviewer Jeffrey Mishlove puts it: you can't even do science without a conscious mind to observe, interpret, and make meaning of data. Consciousness is the precondition for science itself and yet science has no framework to account for it. Chalmers' conclusion is striking: The methods of science may need to be expanded. Consciousness might not be something science explains away. It might be something science has to learn to start with.

Mateus — eu/acc 🇪🇺

32,186 Aufrufe • vor 6 Monaten

MotionGPT: Human Motion as a Foreign Language paper page: Though the advancement of pre-trained large language models unfolds, the exploration of building a unified model for language and other multi-modal data, such as motion, remains challenging and untouched so far. Fortunately, human motion displays a semantic coupling akin to human language, often perceived as a form of body language. By fusing language data with large-scale motion models, motion-language pre-training that can enhance the performance of motion-related tasks becomes feasible. Driven by this insight, we propose MotionGPT, a unified, versatile, and user-friendly motion-language model to handle multiple motion-relevant tasks. Specifically, we employ the discrete vector quantization for human motion and transfer 3D motion into motion tokens, similar to the generation process of word tokens. Building upon this "motion vocabulary", we perform language modeling on both motion and text in a unified manner, treating human motion as a specific language. Moreover, inspired by prompt learning, we pre-train MotionGPT with a mixture of motion-language data and fine-tune it on prompt-based question-and-answer tasks. Extensive experiments demonstrate that MotionGPT achieves state-of-the-art performances on multiple motion tasks including text-driven motion generation, motion captioning, motion prediction, and motion in-between.
0:48

MotionGPT: Human Motion as a Foreign Language paper page: Though the advancement of pre-trained large language models unfolds, the exploration of building a unified model for language and other multi-modal data, such as motion, remains challenging and untouched so far. Fortunately, human motion displays a semantic coupling akin to human language, often perceived as a form of body language. By fusing language data with large-scale motion models, motion-language pre-training that can enhance the performance of motion-related tasks becomes feasible. Driven by this insight, we propose MotionGPT, a unified, versatile, and user-friendly motion-language model to handle multiple motion-relevant tasks. Specifically, we employ the discrete vector quantization for human motion and transfer 3D motion into motion tokens, similar to the generation process of word tokens. Building upon this "motion vocabulary", we perform language modeling on both motion and text in a unified manner, treating human motion as a specific language. Moreover, inspired by prompt learning, we pre-train MotionGPT with a mixture of motion-language data and fine-tune it on prompt-based question-and-answer tasks. Extensive experiments demonstrate that MotionGPT achieves state-of-the-art performances on multiple motion tasks including text-driven motion generation, motion captioning, motion prediction, and motion in-between.

AK

125,353 Aufrufe • vor 3 Jahren

Elon Musk just described a future where money does not exist. Not reformed. Not redistributed. Gone. Musk: “I think things will just be free in the future. If you’ve got an AI robotics economy that is anywhere close to a million times the size of the current Earth economy, literally any need you possibly want can be met.” Forget the sci-fi framing. Listen to what he is actually saying. The entire structure of human civilization runs on a single variable. You need something you cannot freely access. That gap is not a flaw in the system. It is the system. Your employer does not pay you because your work has value. Your employer pays you because you have no choice but to show up. Your government does not protect you out of principle. It maintains order because your dependency on the economy makes you governable. Scarcity is not a natural condition. It is the most successful control structure ever built. Musk: “If you can think of it, you can have it.” Now ask what happens when that structure collapses. A population that does not need a paycheck cannot be managed by one. A population that does not need credit cannot be disciplined by debt. A population that has everything has no reason to comply with anything. This is not a conversation about free goods. This is a conversation about the largest redistribution of leverage in recorded history. But there is a second collapse no one is talking about. Most people have built their entire identity around the constraint. The career they resent is the structure that tells them where to be every morning. The bills they complain about are the exact reason they never had to ask a harder question. Musk: “There actually isn’t money in the future and there’s abundance for everyone.” When the constraint disappears, so does the excuse. The crisis of the coming century will not be material. It will be millions of people standing in total freedom. Discovering they have no idea who they are without the struggle. Every barrier will be gone. And you will finally have to face the one thing scarcity has been protecting you from your entire life. Yourself.
0:43

Elon Musk just described a future where money does not exist. Not reformed. Not redistributed. Gone. Musk: “I think things will just be free in the future. If you’ve got an AI robotics economy that is anywhere close to a million times the size of the current Earth economy, literally any need you possibly want can be met.” Forget the sci-fi framing. Listen to what he is actually saying. The entire structure of human civilization runs on a single variable. You need something you cannot freely access. That gap is not a flaw in the system. It is the system. Your employer does not pay you because your work has value. Your employer pays you because you have no choice but to show up. Your government does not protect you out of principle. It maintains order because your dependency on the economy makes you governable. Scarcity is not a natural condition. It is the most successful control structure ever built. Musk: “If you can think of it, you can have it.” Now ask what happens when that structure collapses. A population that does not need a paycheck cannot be managed by one. A population that does not need credit cannot be disciplined by debt. A population that has everything has no reason to comply with anything. This is not a conversation about free goods. This is a conversation about the largest redistribution of leverage in recorded history. But there is a second collapse no one is talking about. Most people have built their entire identity around the constraint. The career they resent is the structure that tells them where to be every morning. The bills they complain about are the exact reason they never had to ask a harder question. Musk: “There actually isn’t money in the future and there’s abundance for everyone.” When the constraint disappears, so does the excuse. The crisis of the coming century will not be material. It will be millions of people standing in total freedom. Discovering they have no idea who they are without the struggle. Every barrier will be gone. And you will finally have to face the one thing scarcity has been protecting you from your entire life. Yourself.

Dustin

41,906 Aufrufe • vor 5 Monaten

In the Andante movement of Mozart's Piano Concerto No. 21, the "beauty" doesn't lie in a single note, nor in a single expressive moment. It stems from how the entire musical material is organized as a continuous process of tension and resolution, where each event is both the result of what has happened and the condition for what will come next. On the surface, listeners are easily captivated by the softness of the melody, the dialogue between the piano and the orchestra, or the subtle harmonic nuances. However, this is only the phenomenal level. The deeper level lies not in "what the music is," but in "the principles by which the music operates to create the sense of inevitable movement." In Mozart's thinking, no note exists independently. Each sound always carries the aftershock of the previous note and simultaneously creates a tendency towards the next note. It is this continuous movement between tension and release that makes music no longer a series of disconnected events, but a logical flow of movement, where every detail has a reason for existing within the whole. The tension-release mechanism in life Importantly, this mechanism is not unique to music, but reflects a broader structure in human experience. In social relationships, conflict creates an imbalance between people; the process of understanding and adjustment helps restore the stability of the relationship. In biology, the body reacts to threat with a state of tension, and returns to equilibrium when the threat is removed. In psychology, the state of expectation creates mild tension, and completion brings a feeling of relief. At every level, the same pattern can be seen: an unstable state is moved towards a stable state. However, it is important not to understand music as a “simulation of life,” but rather that both music and life can be described by the same principle of organizing experience. Music: where mechanism is refined into structure In classical music, especially in Mozart's compositional thinking, the tension-release mechanism is transformed into a clearly structured language. An unstable note creates a tendency toward a stable note. A chromatic movement creates a sense of deviance from the center. An appoggiatura creates a sense of delay. A modulation to a minor key expands the instability of the entire structure. All these elements do not exist in isolation, but are organized into multi-layered tension-release cycles: microscopic in each note, mesoscopic in each phrase, and macroscopic in the entire structure of the musical movement. The key point is: Mozart did not use these mechanisms to create surprise effects, but to create the feeling that every movement is inherently necessary. This is what creates the seamless and natural flow of the music. Therefore, the beauty in Andante does not lie in a single element, nor in a single compositional technique, but in the tension-release mechanism being organized into a unified system throughout multiple levels of musical structure. At the detailed level, it is present in the relationship between notes and harmonic movement. At the intermediate level, it shapes the structure of each musical phrase. At the overall level, it governs the entire progression of the movement as a unified moving whole. Mozart did not create beauty by eliminating tension, but by organizing unstable states so that they continuously facilitate, guide, and transform into more stable states, thereby forming a dynamic balance throughout the entire musical structure. When these three levels operate simultaneously, the listener no longer perceives "artificiality," but experiences a seemingly natural and continuous flow of movement. It is in this state that the deepest aesthetic value is formed: a sense of a tight, consistent, and inevitable internal order within the sonic timeline.
5:19

In the Andante movement of Mozart's Piano Concerto No. 21, the "beauty" doesn't lie in a single note, nor in a single expressive moment. It stems from how the entire musical material is organized as a continuous process of tension and resolution, where each event is both the result of what has happened and the condition for what will come next. On the surface, listeners are easily captivated by the softness of the melody, the dialogue between the piano and the orchestra, or the subtle harmonic nuances. However, this is only the phenomenal level. The deeper level lies not in "what the music is," but in "the principles by which the music operates to create the sense of inevitable movement." In Mozart's thinking, no note exists independently. Each sound always carries the aftershock of the previous note and simultaneously creates a tendency towards the next note. It is this continuous movement between tension and release that makes music no longer a series of disconnected events, but a logical flow of movement, where every detail has a reason for existing within the whole. The tension-release mechanism in life Importantly, this mechanism is not unique to music, but reflects a broader structure in human experience. In social relationships, conflict creates an imbalance between people; the process of understanding and adjustment helps restore the stability of the relationship. In biology, the body reacts to threat with a state of tension, and returns to equilibrium when the threat is removed. In psychology, the state of expectation creates mild tension, and completion brings a feeling of relief. At every level, the same pattern can be seen: an unstable state is moved towards a stable state. However, it is important not to understand music as a “simulation of life,” but rather that both music and life can be described by the same principle of organizing experience. Music: where mechanism is refined into structure In classical music, especially in Mozart's compositional thinking, the tension-release mechanism is transformed into a clearly structured language. An unstable note creates a tendency toward a stable note. A chromatic movement creates a sense of deviance from the center. An appoggiatura creates a sense of delay. A modulation to a minor key expands the instability of the entire structure. All these elements do not exist in isolation, but are organized into multi-layered tension-release cycles: microscopic in each note, mesoscopic in each phrase, and macroscopic in the entire structure of the musical movement. The key point is: Mozart did not use these mechanisms to create surprise effects, but to create the feeling that every movement is inherently necessary. This is what creates the seamless and natural flow of the music. Therefore, the beauty in Andante does not lie in a single element, nor in a single compositional technique, but in the tension-release mechanism being organized into a unified system throughout multiple levels of musical structure. At the detailed level, it is present in the relationship between notes and harmonic movement. At the intermediate level, it shapes the structure of each musical phrase. At the overall level, it governs the entire progression of the movement as a unified moving whole. Mozart did not create beauty by eliminating tension, but by organizing unstable states so that they continuously facilitate, guide, and transform into more stable states, thereby forming a dynamic balance throughout the entire musical structure. When these three levels operate simultaneously, the listener no longer perceives "artificiality," but experiences a seemingly natural and continuous flow of movement. It is in this state that the deepest aesthetic value is formed: a sense of a tight, consistent, and inevitable internal order within the sonic timeline.

🎼🌺Music Love♥️

12,224 Aufrufe • vor 2 Monaten

Charles Kanjama on whether the DP can run for office or not: The court was not clear on it; it could have been clear by making a declaration that the outcome of the impeachment will not have any consequence. My interpretation is that because the court has found that there has been a violation of the right to a fair hearing, of necessity, the fruits of the impeachment cannot all be sustained. The finality in terms of bringing in a new DP has been sustained, but the other fruits of impeachment, which is to stop the DP from running again, cannot be sustained. The outcome is fairly confusing #CitizenMondayReport
2:12

Charles Kanjama on whether the DP can run for office or not: The court was not clear on it; it could have been clear by making a declaration that the outcome of the impeachment will not have any consequence. My interpretation is that because the court has found that there has been a violation of the right to a fair hearing, of necessity, the fruits of the impeachment cannot all be sustained. The finality in terms of bringing in a new DP has been sustained, but the other fruits of impeachment, which is to stop the DP from running again, cannot be sustained. The outcome is fairly confusing #CitizenMondayReport

Citizen TV Kenya

35,563 Aufrufe • vor 3 Monaten

ALL THIS CONSTRUCTION OF THE VISIBLE WORLD IS AT ITS ROOTS DESIGNED IN THE INVISIBLE WORLD Before language, before numbers, before thought, there was form. Not arbitrary, but precise. Not invented, but revealed. Sacred Geometry is the blueprint beneath all becoming—the hidden grammar of light, sound, and matter. It is the spiral of galaxies and the whorl of a shell. It is the vesica that births light, The triangle that gives rise to stability, The square that anchors space, And the pentagram that mirrors life’s golden proportion. Sacred Geometry does not merely decorate creation, it structures it. It governs the growth of leaves, the pulse of waves, the rhythm of your breath. It reveals that harmony is not a concept, it is a code. A flower blooms not by chance, But by a silent obedience to phi. A crystal aligns not at random, But by listening to the quiet song of symmetry. This is not mysticism, it is order. This is not dogma, it is design. Sacred Geometry is where the visible and the invisible meet: Where math becomes art, Where number becomes movement, Where space becomes spirit. To study it is not only to learn, it is to remember. That beauty is not a luxury. It is the signature of coherence. And when we align with it, We don’t just build structures. We become them. Everything that has form in this dimension is made up in its essence of sacred geometry. All this construction of the visible world is at its root designed in the invisible world.
1:50

ALL THIS CONSTRUCTION OF THE VISIBLE WORLD IS AT ITS ROOTS DESIGNED IN THE INVISIBLE WORLD Before language, before numbers, before thought, there was form. Not arbitrary, but precise. Not invented, but revealed. Sacred Geometry is the blueprint beneath all becoming—the hidden grammar of light, sound, and matter. It is the spiral of galaxies and the whorl of a shell. It is the vesica that births light, The triangle that gives rise to stability, The square that anchors space, And the pentagram that mirrors life’s golden proportion. Sacred Geometry does not merely decorate creation, it structures it. It governs the growth of leaves, the pulse of waves, the rhythm of your breath. It reveals that harmony is not a concept, it is a code. A flower blooms not by chance, But by a silent obedience to phi. A crystal aligns not at random, But by listening to the quiet song of symmetry. This is not mysticism, it is order. This is not dogma, it is design. Sacred Geometry is where the visible and the invisible meet: Where math becomes art, Where number becomes movement, Where space becomes spirit. To study it is not only to learn, it is to remember. That beauty is not a luxury. It is the signature of coherence. And when we align with it, We don’t just build structures. We become them. Everything that has form in this dimension is made up in its essence of sacred geometry. All this construction of the visible world is at its root designed in the invisible world.

🧬Maxpein🧬

13,405 Aufrufe • vor 1 Monat

Martha Nussbaum on why Aristotle believed you are not made of matter. In a 1987 interview on the Great Philosophers, philosopher Martha Nussbaum lays out Aristotle's three-part case against material reductionism, the idea that what you fundamentally are is just the stuff you're made of. His argument is more intuitive than it might sound. First: your matter is always changing. "Matter is always going in and out; it's always changing and of course you do change your material constituents very, very often without ceasing to be yourself." Your cells replace themselves. Your body is not the same collection of atoms it was years ago. And yet you are still you. If your identity were your matter, it would vanish and return constantly. But it doesn't. Something persists that isn't the material. Second: what makes a thing that thing is its function, not its parts. Aristotle uses the example of a ship. Replace some of its planks so long as "its functional structure remains the same, we could always replace bits of the matter without having a different thing in our hands." It's still the same ship. The same logic applies to you. Swap out the components, preserve the structure and function and the identity remains intact. This suggests identity lives in the organisation, not the raw material. Third: matter alone is too vague to define anything. This is perhaps his sharpest point. "Matter is just a lump or heap of stuff and so we couldn't say you are some stuff or other; it's only when we've identified the structure that the stuff constitutes that we can even go on to say something intelligent about the stuff itself." In other words: matter, by itself, tells you nothing. It's formless. You need structure form, function, organisation before you can even begin to describe what a thing is. The deeper implication Aristotle is reaching toward: what makes you you isn't a quantity of carbon and water. It's a pattern. A functional whole. A form that persists through constant material flux. Which raises the question if identity isn't located in matter, where exactly does it live?
0:59

Martha Nussbaum on why Aristotle believed you are not made of matter. In a 1987 interview on the Great Philosophers, philosopher Martha Nussbaum lays out Aristotle's three-part case against material reductionism, the idea that what you fundamentally are is just the stuff you're made of. His argument is more intuitive than it might sound. First: your matter is always changing. "Matter is always going in and out; it's always changing and of course you do change your material constituents very, very often without ceasing to be yourself." Your cells replace themselves. Your body is not the same collection of atoms it was years ago. And yet you are still you. If your identity were your matter, it would vanish and return constantly. But it doesn't. Something persists that isn't the material. Second: what makes a thing that thing is its function, not its parts. Aristotle uses the example of a ship. Replace some of its planks so long as "its functional structure remains the same, we could always replace bits of the matter without having a different thing in our hands." It's still the same ship. The same logic applies to you. Swap out the components, preserve the structure and function and the identity remains intact. This suggests identity lives in the organisation, not the raw material. Third: matter alone is too vague to define anything. This is perhaps his sharpest point. "Matter is just a lump or heap of stuff and so we couldn't say you are some stuff or other; it's only when we've identified the structure that the stuff constitutes that we can even go on to say something intelligent about the stuff itself." In other words: matter, by itself, tells you nothing. It's formless. You need structure form, function, organisation before you can even begin to describe what a thing is. The deeper implication Aristotle is reaching toward: what makes you you isn't a quantity of carbon and water. It's a pattern. A functional whole. A form that persists through constant material flux. Which raises the question if identity isn't located in matter, where exactly does it live?

Mateus — eu/acc 🇪🇺

69,935 Aufrufe • vor 6 Monaten