Comment Re:Why only brains though? (Score 4, Interesting) 35
Finally, recalcitrant peptides are depleted in cytoplasmic and mitochondrial domains and strongly enrichedby up to 16-foldin calcium-dependent phospholipid-binding C2 domains. C2 domains mediate Ca2+-regulated binding of proteins to anionic phospholipids on membrane surfaces, (58) and their enrichment indicates that peptide persistence is disproportionately associated with proteins stabilized at membranes, rather than within freely soluble intracellular compartments. Loss of ionic homeostasis and rising intracellular Ca2+ during post-mortem decay (6) would be expected to further promote sustained membrane association of such proteins. Membrane-adjacent microenvironments are structurally constrained, concentrating redox-active substrates and catalysts (such as lipids and metals) while restricting diffusion and oxygen availability relative to the cytosol. In this context, radical oxidation is less likely to proceed via chain propagation, which requires continuous access to molecular oxygen, (59) and more likely to locally terminate via cross-linking. Such cross-linking would be expected to reduce molecular mobility and solubility, sterically hinder enzymatic and hydrolytic attack, and promote the formation of insoluble aggregates resistant to degradation. (60)
A further factor likely reinforcing this taphonomic trajectory is the brain’s unusually large and heterogeneous reservoir of redox-active iron. (61) Nervous tissue contains high iron concentrations relative to most other soft tissues, distributed across multiple pools such as heme proteins, ferritin-bound stores, and iron-rich compartments associated with mitochondria, myelin, and oligodendrocytes. (62) In life, these pools are tightly regulated to support oxidative metabolism while limiting collateral damage. (63) After death, however, progressive membrane failure and loss of regulatory control are expected to alter iron speciation and availability, increasing the likelihood of local metal-catalyzed radical generation. Importantly, such chemistry need not produce uniform oxidative destruction: when redox reactions involving iron occur within membrane-adjacent or diffusion-limited microenvironments, they may favor the formation of short-lived aromatic radicals that terminate by covalent cross-linking rather than by chain-propagating oxidation (Table S22). The enrichment of peroxidaseswhich often involve heme iron or metal cofactors (64)among recalcitrant peptides is compatible with localized, metal-associated redox chemistry, in which iron-containing cofactors may contribute to peroxide-driven radical formation without sustaining chain-propagating oxidation.
The brain is particularly predisposed to follow this trajectory. In life, it is among the most oxidatively stressed organs: it consumes a disproportionate share of oxygen, is rich in redox-active metals, and relies heavily on antioxidant and repair systems to maintain protein integrity. (65) Additionally, the brain combines extreme membrane density, (66) an abundance of structurally stable, long-lived proteins that accumulate heterogeneous oxidative modifications during life, (67) and anatomical sequestration within the cranial vault. Together, these features establish a post-mortem environment characterized by pre-existing chemical and structural heterogeneity, limited molecular mobility, and restricted oxygen exchange: conditions that favor local, diffusion-limited radical reactions and termination by cross-linking rather than runaway, chain-propagating oxidation. Notably, the molecular features that define this post-mortem pathway closely parallel those that stabilize aggregation-prone protein assemblies in neurodegenerative disease: enrichment of -sheet and structurally ordered fragments, (68) redox-active residue modifications, (69) and oxidative cross-links (70) are hallmarks of pathological protein aggregation in vivo. While the biological contexts differ fundamentally, these parallels indicate that common chemical processes govern protein persistence across clinical and geological time scales.
Comment Re:I'm not convinced QCs will ever work (Score 1) 45
I know that 28 was wrong.
Great. Progress. Now here's the important thing: If you understood Shor's algorithm you would know that 28 couldn't possibly have been the number. So this should cause you to conclude that you are in general overconfident about how much you know or understand about how quantum computers would function. This doesn't mean you are necessarily wrong, but it should indicate that you are overconfident here or could you use a more detailed introduction or refresher on the topic. My preferred recommendation is Aaronson's "Quantum Computing Since Democritus." The book assumes no technical prereqs beyond basic calculus and a tiny amount of linear algebra.
However, you seem to be totally ignorant with regards to algorithmic complexity. That means you do not even have the very basics needed to be in this exchange.
If you think there's some specific indication that I'm in general ignorant about algorithmic complexity, please feel free to point it out. If there's a specific statement I've made that indicates that, by all means show it.
Comment Re: Is Scott Aaronson eating humble pie yet? (Score 1) 45
Comment A bit early in the process? (Score 1) 64
Comment Re:What is the actual last step? (Score 1) 96
Comment Re:I'm not convinced QCs will ever work (Score 2) 45
Comment Re:What is the actual last step? (Score 1) 96
Comment Re:I'm not convinced QCs will ever work (Score 5, Informative) 45
The scaling effort is clearly exponential, hence a total non-starter for anybody that understands computing
Scaling in terms of what? The other user was talking about energy usage. This is pretty obviously not the case. Most forms of quantum computers have to be kept incredibly cold, often in miliKelvin. If there were exponential energy use, then adding even in a few more quantum gates would make that energy total massive. But we don't see that. So by what metric are you claiming exponential scaling effort?
Actually, since QC effort scales exponentially with the length of the computation, one could argue it is trice exponentially worse.
I don't know what "QC effort" is, but the obvious metric for this is just false. For example, Shor's algorithm, which is the algorithm for factoring using a quantum computer, has a number of qubits which scales slightly worse than the square of the number of digits https://en.wikipedia.org/wiki/Shor's_algorithm.
At this time, the qc factoring record (!) is 28. And that is with a no-decision algorithm, i.e. one that knew the outcome before. The next larger effort failed. And the 28 needed many, many repetitions to go though.
This is highly garbled. First, of all the record for factoring cannot be 28, and it cannot be 28 for a pretty obvious reason. Shor's algorithm only works for *odd numbers*. This is a very basic part of how the algorithm functions. The number you are thinking of is 21, not 28. https://arxiv.org/abs/1111.4147. Your point about that these have been "no-decision algorithm" is not completely accurate, but is approximately so. They did use a compiled circuit which used prior knowledge of the solution to optimize the arrangement of the qubits.
But there are also good reasons that factorization records have not expanded. First, Shor's algorithm has high overhead if you trace out the number of gates, and requires very high coherence to even start getting used. It isn't a useful metric of where things are going. This is like looking at the number of people going to space in the 1950s when no one has gone to space and ignoring that rockets had been steadily improving since the 1930s. The coherence time for quantum computers continues to improve. For a while it was improving at a rate of a factor of 10 roughly every 3 years https://en.wikipedia.org/wiki/Quantum_computing_scaling_laws#Schoelkopf's_law . That has slowed down in the last decade or so, so it is now improving by about a factor of 3 to 5 every 3 years. Similar remarks apply to other metrics like number of gates. And we know that if you can get error levels down and coherence times long then quantum error correcting codes https://en.wikipedia.org/wiki/Quantum_error_correction works. In particular, the threshold theorem https://en.wikipedia.org/wiki/Threshold_theorem says that once your physical error rate is low enough, the logical error rate can be as low as you want, regardless of the size of the computation.
Comment Re:I'm not convinced QCs will ever work (Score 1) 45
I have nothing to base my gut feeling on other than I don't believe the laws of physics will give us all the supposed magic parallel information processing for so little energy expenditure in effect almost for free. I'm prepared to be proven wrong but right now I don't think I am.
It isn't unreasonable to have this gut reaction to how quantum computers are described frequently to the general public. But one important thing to realize is that they don't let you do magic parallel information processing. There's this way of describing them as "trying all solutions at once," or things like that. But a quantum computer cannot in general do that, since if one has all potential "solutions" one needs some way of making sure that the non-solutions cancel out. In that context. there are some problems where we can do that, such as factoring numbers via Shor's algorithm https://en.wikipedia.org/wiki/Shor's_algorithm. Even there, what is going on is more subtle than just trying all factorizations, as noted by the number of quantum gates needed scaling at slightly worse than the number of binary digits of the number. If it were just trying everything in parallel this would scale close to linear with the total number of gates.
A different related situation to look at which may also be useful is how we strongly suspect that NP problems cannot be efficiently solved on a quantum computer. In particular, that NP is not contained in BQP https://en.wikipedia.org/wiki/BQP, the set of problems which can be done efficiently on a quantum computer. If a quantum computer could do "magic parallel information processing" then we'd expect NP to be contained in BQP.
Comment Re:Is Scott Aaronson eating humble pie yet? (Score 4, Interesting) 45
Comment Re:Can we please get that crash soon? (Score 1) 46
I do not think you know what "doing mathematics" means.
I'm reasonably confident I have a pretty good understanding of what doing math is like given that I'm a published mathematician. Heck, I'll be a little egotistical and just to my own recent paper directly https://cs.uwaterloo.ca/journals/JIS/VOL29/Zelinsky/zel14.html. But this also isn't terribly relevant.
All LLMs can really do for mathematics is better searching.
LLMs have been very good at doing searches. But they've done a lot of things that are pretty obviously not mere searches. For example, in the case of Erdos 1196, the LLM solution constructed a Markov chain using a weighing via the von Mangoldt function https://en.wikipedia.org/wiki/Von_Mangoldt_function. That wasn't in the literature at all. In the case of the Jacobian Conjecture for n=3, the AI constructed a complicated polynomial which was certainly not in the literature, since the entire reason the polynomial is of interest is as a counterexample to the Jacobian conjecture.
. Incidentally, even a fields medal does not usually qualify you do understand LLMs. But many experts in one field have no understanding of how limited their insight is in another. So, yes, I am absolutely not above to call a fields medal winner that makes a stupid statement about LLMs a "moron"
It is true that a Fields Medalist does not imply expertise in other areas. But these are people who have also spent time working with these systems. And understanding *how* an LLM functions in this way isn't as important as them being able to see what the system can do. One can evaluate that a black box is useful for specific purposes without knowing anything about how the black box functions. And this is not just the Fields Medalists, this is almost the entire community of mathematicians, including people like the one I linked to who is explicitly very anti-AI. This doesn't mean that they are necessarily correct by itself. But it should be a pretty serious warning that these are not mere "morons" here and that you possibly are just mistaken about what capabilities these systems have.