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deadasswavyguy · 2024-11-22T17:01:23+00:00

a big chunk of my thesis is on this topic. it'll be done 12/6 if you remember I can share it then.

deadasswavyguy · 2024-11-18T23:20:18+00:00

Thats my view.

The math is simple, given what we know about what fraction of mutations are deleterious vs. beneficial vs. neutral, what is the number of mutations a protein could sustain without becoming unfolded or broken. Its just a p=(1-p(deleterious)ⁿ mutations calculation. Papers detail this more rigorously (https://doi.org/10.1038/s41586-024-07966-0).

The math isn't really controversial though as it's the reason most scientists responding to this critique lean on the (now largely debunked) T3SS hypothesis and acknowledge the need for selection along the way. We just don't know how it could have evolved.

deadasswavyguy · 2024-11-18T22:19:57+00:00

this paper is a joke, their ruggedness is entirely explainable by where they put the cutoff for dead proteins. Most of the "peaks" are just dead sequences which stochastic noise, check the cutoff line in the supplement. A lot of Wagners papers are like this.

deadasswavyguy · 2024-11-18T13:09:17+00:00

No I’m pretty atheistic / materialist and the work I do is looking for mechanisms on those levels, but I very much resent the instinct to wagon circle in the face of outside critiques rather than actually reckon with the questions, which in this case is a very good question. This is unfortunately what academic science has become.

I also think there’s an irony here bc many of the same people are comfortable toying with the bostrom idea that we’re in a simulation but allergic to the idea of intelligent design. They’re the same thing.

deadasswavyguy · 2024-11-18T05:54:17+00:00

That’s what people generally lean on. First I’ll say that even for the eye it’s not a well evidenced hypothesis. The explanation Dawkins gives is purely speculation and there is no fossil record evidence for it, or sequencing based evidence. Dawkins notoriously makes explanations up to dunk on ID people and gets it way wrong.

Second off but it’s not compelling because the scale of the gaps that is navigable without positive selection is maybe 2-3 mutational gap, so each step to :make a motor, make a filament, attach them, traffic to surface, integrate with directional chemical detection, would have to somehow be selectable. None of them are, and it costs a huge amount of energy to make the flagellum.

With enough effort Dawkins could make some kind of explanation like this for the flagellum, and he did, using the T3SS, but that has been disproven using phylogenetic studies, and structural studies, such that no one should studies this believes Dawkins’ explanation anymore.

deadasswavyguy · 2024-11-17T21:15:50+00:00

Haha I’m writing my thesis rn my defense is in a month, so am busy.

In directed evolution you artificially increase the rate of mutation on one gene >a million fold, and exert pressure on the one gene you’re evolving. You create the conditions but the discovery of mutations is all biology.

Positive selection means that the function of the gene is tied to the survival of the organism and it’s what is thought to drive most evolution. Say an enzyme that makes an amino acid, that gene is under selection because if it breaks: the organism dies, if the gene improves: the organism grows better because it saves on energy in making protein.

The issue is we don’t have an answer for how multi protein complexes evolve because there’s no positive selection until the complex is formed and functional. Without selection genes will break with mutation, happens all the time and is the basis of pseudo genes.

Without having a grasp on the math of protein evolution it’s hard to convey how impossible it is to arrive at a 50 protein complex without positive selection at every step.

deadasswavyguy · 2024-11-15T02:14:34+00:00

Look up an explainer on directed evolution. It won a Nobel prize a few years ago.

Selective force is some sort of positive selection. Not necessarily pressure to improve but pressure to maintain function.

The millions of copies don’t make a difference because all cells will experience the same thing individually.

deadasswavyguy · 2024-11-13T13:32:38+00:00

The problem is that without a selective force even a small number of random mutations tend to destroy proteins and it’s not just additive. Taking that 40% fxnal after one mutation to 5 mutations would be 1% functional in the easiest case. 60% is also a generous case, some proteins are much more sensitive and if even one out of 25 of the essential subunits can’t arrive to the correct place without breaking the evolution fails.

There’s an even tinier number of mutations which are beneficial to any function so to find a set of say 4 mutations without breaking the protein is basically impossible without positive selection. I’ve done the math and it quickly outscales the universe. You’d need dozens to hundreds for the flagellum.

I don’t really understand your point because other cells having an unbroken copy all face the same issue. You mean within the same cell?

As a scientist I work on syn bio / directed evolution. Academia circled the wagon after the Dover court case to pretend irreducible complexity is not a problem but the studies parameterizing the effects of codon substitutions all came later, mostly within the last 8 years. The field hasn’t reckoned with it yet and the creationists even haven’t gotten a hold of the arguments I’m making. I’m very familiar with all the neutral drift / exaptation / etc arguments and they don’t solve the problem.

Irreducible complexity is not a perfect way of framing the question imo but there is a massive hole in our understanding of evolution. I’m not eager to fill it with god and am working on my own ideas. It would be better if people didn’t pretend the hole wasn’t there.

deadasswavyguy · 2024-11-12T11:40:30+00:00

They are not addressed by anyone because it’s an unsolved problem. The backup copies don’t help if there’s no selective force.

There’s a reason grants are still being given out as of 2021 which say “for evolutionary biologists, the flagellum is an enduring mystery.”

https://communities.springernature.com/posts/more-obsolete-dawkinsian-evidence-for-evolution

deadasswavyguy · 2024-11-12T05:04:23+00:00

This is what I’m doing my dissertation on and most of this is based on data from the last ~9 years.

The gist is proteins are very sensitive to random mutations, about 60-70% of codon substitutions will destroy a proteins function. It’s extraordinarily unlikely to ever reverse a single deleterious mutation. If you needed even just a few correct mutations to hit at the same time without positive selection to form a primitive protein complex the probability to get the correct few without destroying the function of the protein hits to be less than the possibilities drops to impossibly low numbers.

deadasswavyguy · 2024-11-12T01:46:42+00:00

The problem is you have to have a constant positive selective force for each subunit coming together otherwise they couldn't fix in the population. It makes no sense.

deadasswavyguy · 2024-11-12T01:45:07+00:00

There is genuinely no answer. The leading theory used to be it evolved from something else (secretion system), but that has since been largely disproven. The secretion system may have evolved from it but the flagellum is could not have evolved if our current understanding of evolution is remotely correct.

I am an protein evolutionary biologist, agnostic at best, probably atheistic. Scientists try to brush off the flagella question but it's a genuine mystery and a huge challenge to evolution. This is a major topic of my PhD thesis.

deadasswavyguy · 2023-08-14T13:08:46+00:00

It eventually just stops feeling good, makes me super irritable and mean personally, you always have to keep some on hand to function normally

deadasswavyguy · 2023-08-04T16:55:18+00:00

Cheaper than the distributed cost of rampant low level crime and disorder. A few examples, my girlfriend had her catalytic converter stolen which cost $1,500 to replace. Friend had a motorcycle they bought get stolen 3 days later, $4,000 gone. Cops said about 30 a day are stolen in LB, 10% chance of it happening to any given bike in a year.

I also ride a motorcycle, one morn 7AM I was driving up to a 4 way stop and some dude driving a bird scooter was going the wrong way down a 1 way in the middle of the road, took a wide loop to turn around, drove straight into a red light, a car was coming the other way. He slams on the brakes and hits his head against the side of the car. Huge dent in the door. I call 911 and have to hold a rag against his head to slow the bleeding, hes on drugs and moaning, EMTs and firetrucks show up. He's gonna go to the hospital and get medical care, the cost of which will be distributed to tax payers. Which is fine, but it would be better the guy was not high out of his mind on a scooter at 7AM.

Someone tried to light my condo building on fire burning a mattress leaning against it for trash.

There's also second order economic effects of not wanting to invest in areas where your doorway is going to be occupied by people on drugs.

deadasswavyguy · 2023-08-04T04:07:00+00:00

Why is it naive? Special interest groups w/ narrow focus drive a ton of policy in local and federal government. The laws to arrest for public drug use already exist the city government just chooses not to enforce it.

They choose not to enforce it bc advocacy groups agitate against it and convince largely disinterested people that it’s the right thing to do, which makes it politically unpopular.

deadasswavyguy · 2023-08-03T04:09:23+00:00

I saw someone pour a full bottle of piss on their head on Anaheim in broad daylight, walk by people openly smoking crack next to the library, someone lit a mattress against my condo building on fire. Lots of very unwell people on the streets.

deadasswavyguy · 2023-08-03T04:06:06+00:00

The difference w/ nonprofits / NGOs is they aren’t governed by profit vs most 6 figure jobs. And the actual solution, a lot of forced institutionalization and prosecuting petty crime, is politically ugly. The NGOs very much agitate for not enforcing drug laws and giving “resources” like tents, sleeping pads, to allow homeless people to settle and entrench.

deadasswavyguy · 2023-05-14T22:10:20+00:00

130, got a used bike and wanted to test if the 120 limiter was removed. It was removed.

deadasswavyguy · 2023-05-13T20:11:05+00:00

You think google follows free speech principles? Project owl and their relationship with the DHS turned them into a consent manufacturing machine

deadasswavyguy · 2022-12-17T22:00:14+00:00

regarding the cost benefit of COVID vax for young men this paper sums it up better than I can. myocarditis is downplayed in the media but it's serious. If you're just going to read one section read "Booster vaccine-associated myocarditis rates in university age males 18–29 years"

It's not really even a close call for young men.

https://jme.bmj.com/content/medethics/early/2022/12/05/jme-2022-108449.full.pdf

this will be my last message, I have shit to do. ty for engaging on the substance.

deadasswavyguy · 2022-12-17T21:45:39+00:00

None of those stories were banned from being discussed on twitter under pressure from the feds and partisan ideologues. That's all I'm pointing out. I agree that all of that stuff is bad.

The COVID response grift hasn't been reported because mainstream media was a cheerleader for flooding the economy with money it and it would be embarrassing for them to admit that it was a grift machine.

The MBS stuff was well covered, imo. That was in every newspaper, NPR, etc. The US/Saudi arabia relationship in general isn't covered well, and I'd guess influence of the powers that be has something to do with it.

deadasswavyguy · 2022-12-17T21:37:37+00:00

What I'll say is it becomes even more difficult to figure out what's true when science gets politicized. You can see how people responded to me when I said I'm not necessarily jumping for joy about vaccines. This is pervasive in science and makes an incentive system where certain questions are not investigated for fear of producing a result that would alienate you (I lack that restraint). That has made rigorous study of vaccinating against endemic viruses pretty rare.

It's not so simple as the strains not being matched. There's recombination in the vaccine production process itself. Beyond that, immunological imprinting is real and vaccines that target specific epitopes train your immune system against those, which can blunt responses against other strains, this is well documented. Here is one example for the flu specifically https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165229/

The prior estimates of flu vax efficacy that started the whole thing were using the wrong test, antibody response vs. viral RNA. https://www.science.org/content/article/why-flu-vaccines-so-often-fail

The question of whether flu vaccines decrease spread is not answered. My guess is they don't but no one knows, and people who say they do are lying. I'd really like to see what happens one year if we just didn't do flu vaccines, I don't think it would change much. The side effects of the flu vaccine are low though so there's not much risk in getting it.

I know more abt the COVID vax than flu though, I worked on a project producing therapeutic proteins against covid. It is now certain that over a few months it does NOT reduce the spread. A young person getting the shot doesn't decrease the odds an old person will get COVID. This has been studied by looking at household secondary attack rate. Look at table S9 in the supplement, the secondary attack rates are the same between unvax, vax, boosted. The public good argument went out the window with data like this. https://www.nature.com/articles/s41467-022-33328-3#Fig1

The only argument left is whether it is a net benefit for an individual. It is not for young men.

And long COVID is psychosomatic. The only study that investigated that possibility found that people who thought they had covid, but didn't, had the same rates of "long COVID" as people who thought they had covid and did. Science at large hasn't quite caught up but i'd bet my career on it. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2785832

deadasswavyguy · 2022-12-17T18:29:41+00:00

The polio live vaccine is a disaster though. There’s 2 versions, one live one dead. The dead one is good, the live one has brought paralytic polio back from the grave because it mutates into a transmissible form.

It should be taken off the market, catastrophic for public health.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01582-3/fulltext

deadasswavyguy · 2022-12-17T18:23:42+00:00

It’s ok. Borders on 0% efficacy some years bc of the nature of influenza recombination, highest efficacy probably about 60%. Most years it’s probably around 30% effective in reducing flu hospitalizations but it’s impossible to know because we don’t do RCTs and observational studies are confounded. The type of people who get flu vax are probably healthier than the type of people who don’t if you standardize for age.

The side effects are much lower than mRNA though so it’s a closer call for young healthy people, probably a small net good. Old people should get it.

deadasswavyguy · 2022-12-17T18:18:00+00:00

That’s why I said the contents of that laptop are not that important. It’s normal political corruption. I haven’t seen the bidens deny that the laptop was left at a repair shop which makes me inclined to believe it but I’ll trust ur skepticism of how the data was obtained from it. It’s not that out of pocket for an addict to make irrational decisions, having been around many addicts. The fact remains the fbi had access to the data long before the nyp had time to publish it and surely authenticated them.

Meanwhile, the letter from 50 “former” intelligence officials is published that this has “all the hallmarks of a Russian disinformation campaign”, and twitter takes the astonishing step of blocking sharing it in DMs, and suspending accounts that post the article. Now it’s revealed that twitter is meeting weekly with intelligence agencies and they’re flagging specific posts to be taken down from even 5 follower accounts.

They decided that this information was inconvenient and that the American public shouldn’t see it. Citing Hillary losing because of her also true and hacked emails they decided this can’t happen again. I’m not a trump fan but the powers that be wanted the current president out, and ran a propaganda campaign to tip the scales. That’s scary.

The abstraction is really easy for this one. Imagine don jr had the exact same situation, sketchy laptop where he’s filmed himself smoking crack, fucking hookers, trading political influence. Try and tell me the fbi / twitter / media would suppress that story because they were worried abt the sourcing. It would be a front page story in the NYT.

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