Register | Sign In


Understanding through Discussion


EvC Forum active members: 65 (9162 total)
6 online now:
Newest Member: popoi
Post Volume: Total: 915,815 Year: 3,072/9,624 Month: 917/1,588 Week: 100/223 Day: 11/17 Hour: 0/0


Thread  Details

Email This Thread
Newer Topic | Older Topic
  
Author Topic:   Extent of Mutational Capability
CRR
Member (Idle past 2242 days)
Posts: 579
From: Australia
Joined: 10-19-2016


Message 226 of 279 (797475)
01-22-2017 12:24 AM
Reply to: Message 224 by Dr Adequate
01-21-2017 10:54 PM


Re: The Maths
Nevertheless Doc, you've managed to disprove your first position.

This message is a reply to:
 Message 224 by Dr Adequate, posted 01-21-2017 10:54 PM Dr Adequate has replied

Replies to this message:
 Message 227 by Dr Adequate, posted 01-22-2017 1:36 AM CRR has replied

  
Dr Adequate
Member (Idle past 284 days)
Posts: 16113
Joined: 07-20-2006


Message 227 of 279 (797478)
01-22-2017 1:36 AM
Reply to: Message 226 by CRR
01-22-2017 12:24 AM


Re: The Maths
Nevertheless Doc, you've managed to disprove your first position.
No.
Why would you say such a bizarre thing?

This message is a reply to:
 Message 226 by CRR, posted 01-22-2017 12:24 AM CRR has replied

Replies to this message:
 Message 234 by CRR, posted 01-27-2017 3:33 AM Dr Adequate has replied

  
caffeine
Member (Idle past 1024 days)
Posts: 1800
From: Prague, Czech Republic
Joined: 10-22-2008


Message 228 of 279 (797481)
01-22-2017 5:42 AM
Reply to: Message 221 by CRR
01-21-2017 9:46 PM


Re: Look Sharp
On the other hand the chance of a bridge player getting dealt 13 cards of the same suit in order is so small (~1/10^60) it might never have happened, at least with a properly shuffled deck. (I hope I got my maths right)
I don't think you did. I got approximately 1/10^21. That's based around getting A-K, in order, of any suit. (4/52*1/51*1/50*....*1/40).

This message is a reply to:
 Message 221 by CRR, posted 01-21-2017 9:46 PM CRR has not replied

  
NoNukes
Inactive Member


(2)
Message 229 of 279 (797485)
01-22-2017 9:07 AM
Reply to: Message 223 by CRR
01-21-2017 10:33 PM


Re: Look Sharp
Yes, if the cards can be in any order it changes the odds a lot. Bridge probably has a similar problem to whist in that you have to follow suit where possible and shuffling between hands might not be perfect.
Isn't the probability exactly the same for any specified order of cards? Singling out an order in which the cards are dealt to each player in order, suggests that there is just one possible ordering to consider. Single ordering does not model abiogenesis because multiple resulting orders may be possible with only the sharpshooter's fallacy forcing you to so focus. And that's just the case for having random arrival without any selection or replication process that preserves useful orders which also does not model the proposed process very well.

Under a government which imprisons any unjustly, the true place for a just man is also in prison. Thoreau: Civil Disobedience (1846)
History will have to record that the greatest tragedy of this period of social transition was not the strident clamor of the bad people, but the appalling silence of the good people. Martin Luther King
I never considered a difference of opinion in politics, in religion, in philosophy, as cause for withdrawing from a friend. Thomas Jefferson
Seems to me if its clear that certain things that require ancient dates couldn't possibly be true, we are on our way to throwing out all those ancient dates on the basis of the actual evidence. -- Faith
Some of us are worried about just how much damage he will do in his last couple of weeks as president, to make it easier for the NY Times and Washington post to try to destroy Trump's presidency. -- marc9000

This message is a reply to:
 Message 223 by CRR, posted 01-21-2017 10:33 PM CRR has not replied

  
Percy
Member
Posts: 22391
From: New Hampshire
Joined: 12-23-2000
Member Rating: 5.2


(1)
Message 230 of 279 (797489)
01-22-2017 10:02 AM
Reply to: Message 221 by CRR
01-21-2017 9:46 PM


Re: Look Sharp
CRR writes:
So even with those vast probabilistic resources the odds are fantastically small that a protein could have formed by chance.
I think you'll get broad agreement that "the odds are fantastically small that a protein could have formed by chance," regardless of whose calculation of the odds is correct. The odds of random formation aren't relevant because proteins don't form by chance They're constructed in cells according to the blueprint provided by DNA.
We don't know what the first proteins were like, but we don't think they came about by chance. We don't think life is some fantastically unlikely accident.
--Percy

This message is a reply to:
 Message 221 by CRR, posted 01-21-2017 9:46 PM CRR has not replied

  
RAZD
Member (Idle past 1405 days)
Posts: 20714
From: the other end of the sidewalk
Joined: 03-14-2004


(1)
Message 231 of 279 (797491)
01-22-2017 10:36 AM
Reply to: Message 221 by CRR
01-21-2017 9:46 PM


Reality check
On the other hand the chance of a bridge player getting dealt 13 cards of the same suit in order is so small (~1/10^60) it might never have happened, at least with a properly shuffled deck. (I hope I got my maths right)
As has been discussed (a) this math is wrong and (b) it is much smaller than the chances of being dealt 13 cards of the same suit in ANY order. Can you tell me the functional difference between getting them all in one order or them arriving in any order? Can I suspect that you will agree that functionally they are the same?
In terms of winning in bridge I can replace the deuce with an ace from any other suit and still have a grand slam. I can replace the trey with another ace and the four with the third ace, then I can start replacing other low cards with kings ... and still have a grand slam.
SO there are many functionally equivalent combinations of cards that will produce the desired effect.
Douglas Axe has estimated the chance of a chain of amino acids forming a functional protein is ~1 in 10^77. ...
I recommend you read the the old improbable probability problem thread:
quote:
We see them over and over .... this or that could not possibly have happened because the improbability is just too great.
Usually these are based on very restrictive "all-at-once-out-of-nothing" linear calculations where the errors involved are multifold and pervasive:
Curiously I wrote that article in 2004, and as yet see no reason to make any corrections or adjustments.
Next, in order to have a better understanding of the biology of where and when proteins were evolved, I suggest you read Panspermic Pre-Biotic Molecules - Life's Building Blocks (Part I)
quote:
My Conclusions
From these information sections it seems to me that the building blocks needed for beginning the creation of life were plentiful, not just on Earth but in space in general and from the earliest of times. Probably they have been around since long before even the Earth formed from the cosmic debris left behind by the life and death cycle of previous stars and planets, back to the beginning of time. These "seeds of life" no doubt extend through the far reaches of the universe as well as the depths of time (cue Crosby, Stills, Nash and Young ... "We are star dust ...").
and Self-Replicating Molecules - Life's Building Blocks (Part II)
quote:
This does not explain all the questions of how life developed on earth over 3.5 billion years ago, but it goes a long way in showing how possible it was for life to develop from existing chemicals in the conditions that existed in the pre-biotic earth. The sheer number of possibilities also can hint that such processes were quite active, with many variations vying for resources, and that the replication system that life developed from was likely the best at self-replication - the fastest, most stable and aggressive replicators outcompeting their competitors. The likelihood is that, even if they had not existed, that another replication system would have been able to develop into life. Some initial elements of evolution - random variation and feedback selection - were evident in this pre-biotic world.
To my mind "life" began when evolution -- mutation and selection -- began to operate.
You can read more on this in Axe's "Undeniable".
Why should I read something that starts with an erroneous preposition?
Enjoy

we are limited in our ability to understand
by our ability to understand
RebelAmerican☆Zen☯Deist
... to learn ... to think ... to live ... to laugh ...
to share.


Join the effort to solve medical problems, AIDS/HIV, Cancer and more with Team EvC! (click)

This message is a reply to:
 Message 221 by CRR, posted 01-21-2017 9:46 PM CRR has not replied

  
dwise1
Member
Posts: 5930
Joined: 05-02-2006
Member Rating: 5.8


Message 232 of 279 (797500)
01-22-2017 4:30 PM
Reply to: Message 221 by CRR
01-21-2017 9:46 PM


Re: Look Sharp
Douglas Axe has estimated the chance of a chain of amino acids forming a functional protein is ~1 in 10^77. Denton estimates that no more than 10^40 proteins have ever existed on Earth. So even with those vast probabilistic resources the odds are fantastically small that a protein could have formed by chance. (obviously there are lots of assumptions and boundary conditions in any estimates of this kind). Pro-evolution researchers have done estimates and come up with the chance forming a functional protein as ~1 in 10^50. However that still leaves the chance at ~1/10^10 so it remains fantastically improbable. Note this avoids the sharpshooter fallacy because any functional protein would be success.
You can read more on this in Axe's "Undeniable".
I have seen this claim made for decades, so, no, I will not buy that book just in order to read the same false claim yet again.
Just making bare assertions and bare links instead of presenting the argument is frowned upon here. That is basically what you have done, minus any links (just naming an ID book is less than a bare link).
Here is a reply I posted on CompuServe two decades ago. Please let us know whether Axe's claim is different than Charles Wagner's was and describe how they are different:
quote:
#: 230849 S4/Biology
20-Feb-96 21:15:48
Sb: #229253-Lamarquian Evolution
Fm: David C. Wise 72747,3317
To: charles wagner 72401,2203
> Take for example a hypothetical polypeptide enzyme composed of 20
> different amino acids. These amino acids must be in the correct order and
> of the correct kind for the enzyme to work. The first amino acid has a 1:20
> chance of being correct. Same with the second and third anon... This gives
> us a probability of randomly discovering the correct sequence as about
> 10e20. Now there are about 2000 enzymes needed for a mammal to function.
> This gives us a probability of 10e40000 of finding them all by random
> trial and error. The earth is about 10e17 seconds old. How many mutations
> would have had to occur to get where we are?
Your first mistake is in assuming, quite incorrectly, that one and only one
amino acid sequence would be correct and any variation in that sequence would
be non-functional. Human lysozyme, chicken lysozyme, and bullfrog lysozyme all
have different amino acid sequences and yet are still the same protein,
lysozyme (BTW, human and chimpanzee lysozyme are identical). Human and
rattlesnake cytochrome c differ from each other by about 14 amino acids,
rattlesnake cytochrome c differs even more from cytochrome c in other species
(in the Dayhoff study, which included no other snakes, the rattlesnake protein
happened to be slightly more similar to the human protein than to the other 15
or so species in the study, which gave rise to a particularly and intentionally
deceptive creationist claim), and human and rhesus monkey cytochrome c differ
by 1 amino acid (which the creationist claim carefully avoided mentioning), and
yet it is still cytochrome c. I have a protein database with many more such
examples.
From the class notes of Frank Awbrey & William Thwaites' creation/evolution
class at UCSD (the Institute for Creation Research conducted half the lectures
and Awbrey & Thwaites the other half), we read their response to Duane Gish's
standard argument which you have repeated here. Gish calculates the
probability of a replaceable pool of 20 amino acids randomly forming into
RNAase with 124 amino acid sequences as:
Prob = (1/20)^124 = 1/3.4 x 10^(-166).
His basic assumptions, identical to yours, are:
1. each amino acid is uniquely specified.
2. parts of proteins serve no useful purpose
Evolutionist response:
1. only a few amino acids in a protein are uniquely specified, many are
loosely specified, and many are not specified at all; eg, in hemoglobin,
although sickle cell trait involves only one amino acid substitution, 17
other hemoglobin variants are known which are not harmful -- these have
substitutions at nonessential sites.
2. parts of proteins may well have serve useful functions in primitive
life forms.
A&T point out that there are different classes of amino acids: hydrophyllic,
hydrophobic, charged, uncharged, etc, and that for many amino acid positions it
is the class of amino acid and not the amino acid itself that is important.
Their counter example is of a calcium binding site with 29 amino acid
positions: only 2 positions require specific amino acids, 8 postions can be
filled by any of 5 hydrophobic amino acids, 3 positions can be filled by any
one of 4 other amino acids, 15 of the positions can be filled by virtually any
of the 20 amino acids.
The sequence of the 15 positions is: L* L*L* L*D D* D*G* I*D* EL* L*L* L*
Where:
L* = hydrophobic - Leu, Val, Ilu, Phe, or Met Prob = (5/20)^8
D* = (a) Asp, Glu, Ser, or Asn Prob = (4/20)^3
(b) theoretically also Gls or Thr Prob = (6/20)^3
D = Asp (1/20)
E - Glu (1/20)
G* = Gly or Asp (2/20)
I* = Ilu or Val (2/20)
Total Prob = (a) 3.05 x 10^(-12)
(b) 10.2 x 10^(-12)
By Gish's (and your) method: (1/20)^29 = 1.86 x 10^(-38)
So you see that the world and its probabilities work quite differently that
Duane Gish and you imagine it to.
Your second mistake should have been covered in your biology courses. Each
generation's proteins are not specified de novo and randomly, but rather each
generation inherits the previous generation's encoded sequences with the
possibility of some random changes. Of course, you can now see that several
sites in those sequences can suffer base substitutions very gladly and still
produce functional proteins. Indeed, we repeatedly find that the degree of
difference found between the proteins of different species fits very well what
we would expect had they descended from a common ancestor (AKA "evolved").
These patterns show up even when one tries to demonstrate otherwise, as in the
case of Michael Denton (whose attempts to disprove the standard phylogenetic
trees by grouping species according to the degree of difference between their
corresponding proteins only resulted in the very same standard phylogenetic
trees that he was trying to disprove).
Come to think of it, how does your panspermia account for the patterns of
relatedness shown by protein comparisons, or for pseudogenes, pieces of "junk"
DNA that are only shared by related species?
And as for the very first such protein having to have formed at random,
research by Sidney Fox shows that, when heated, amino acids form quite readily
into short proteins which, in the presence of water, form into microspheres.
These microspheres are very stable, so long as there are no micro-organisms
about to eat them. Many of these microspheres also display catalytic activity.
All that is missing at this point is a mechanism for replicating these thermal
proteins, after which the power of cumulative selection could be brought to
bear.
Which brings us to your third mistake. You assume that life would operate by
single-step selection whereas it is blatantly obvious that life operates by
cumulative selection. As much as you would love to discount my MONKEY, it does
still demonstrate, through a controlled experiment, the immensely vast
probability difference between the single-step and cumulative selection
methods. Your single-step example would indeed be very improbable and require
an immense time-span to produce results, whereas cumulative selection would
succeed in a matter of generations.
Bottom line:
  1. In order to mean anything, a mathematical model must actually describe what it's supposed to be model. These creationist protein probability claims do nothing of the sort.
  2. Nobody but creationists claim that proteins are the products of amino acids just happening to have fallen together by pure chance. Rather, they evolved, which is something quite different.
PS
I mention and contrast single-step selection and cumulative selection. If you are not familiar with those concepts and how they differ, then read the first half of Chapter 3, "Accumulating Small Change", of Richard Dawkins' The Blind Watchmaker.
Or you could go to my page, MONKEY, in which I discuss my own implementation of Dawkins' WEASEL program and link to my MPROBS.DOC file which analyzes and discusses the probabilities involved in cumulative selection. Basically, creationists keep using single-step selection whose probability of success are abysmally small, whereas evolution uses cumulative selection which succeeds with extreme rapidity and certainty. So far, the creationist attempts I've seen to "disprove" both WEASEL and MONKEY rely on lying about how they work (which I discuss on that page).
Edited by dwise1, : PS

This message is a reply to:
 Message 221 by CRR, posted 01-21-2017 9:46 PM CRR has not replied

  
Coyote
Member (Idle past 2106 days)
Posts: 6117
Joined: 01-12-2008


Message 233 of 279 (797501)
01-22-2017 4:52 PM
Reply to: Message 221 by CRR
01-21-2017 9:46 PM


Genetic networks
Douglas Axe has estimated the chance of a chain of amino acids forming a functional protein is ~1 in 10^77. Denton estimates that no more than 10^40 proteins have ever existed on Earth. So even with those vast probabilistic resources the odds are fantastically small that a protein could have formed by chance.
Here is an online lecture that I've posted to these threads before that demonstrates that the odds cited by creationists do not reflect reality. It is an hour long, so I can't post much here beyond the abstract:
Abstract: Mathematical computer models of two ancient and famous genetic networks act early in embryos of many different species to determine the body plan. Models revealed these networks to be astonishingly robust, despite their 'unintelligent design.' This examines the use of mathematical models to shed light on how biological, pattern-forming gene networks operate and how thoughtless, haphazard, non-design produces networks whose robustness seems inspired, begging the question what else unintelligent non-design might be capable of.
Making Genetic Networks Operate Robustly: Unintelligent Non-design Suffices, by Professor Garrett Odell
https://www.youtube.com/watch?v=EsbKzFdW2bM

Religious belief does not constitute scientific evidence, nor does it convey scientific knowledge.
Belief gets in the way of learning--Robert A. Heinlein
In the name of diversity, college student demands to be kept in ignorance of the culture that made diversity a value--StultisTheFool
It's not what we don't know that hurts, it's what we know that ain't so--Will Rogers
If I am entitled to something, someone else is obliged to pay--Jerry Pournelle
If a religion's teachings are true, then it should have nothing to fear from science...--dwise1
"Multiculturalism" demands that the US be tolerant of everything except its own past, culture, traditions, and identity.

This message is a reply to:
 Message 221 by CRR, posted 01-21-2017 9:46 PM CRR has not replied

  
CRR
Member (Idle past 2242 days)
Posts: 579
From: Australia
Joined: 10-19-2016


Message 234 of 279 (797777)
01-27-2017 3:33 AM
Reply to: Message 227 by Dr Adequate
01-22-2017 1:36 AM


Re: The Maths
At Message 176 you posted a copy of sfs's post claiming that genetic drift could explain the difference between human and chimp genomes. At Message 195 you showed that you were talking about fixed mutations.
My argument was that taking mean time to fixity into account meant that less than half of the mutations could have been fixed in that time.
At Message 203 you presented what appeared to be the same argument from a different perspective. Once again I showed that not all of the mutations could possibly have been fixed by drift.
You are going to have to do a lot more to show that genetic drift is a plausible explanation for the genetic difference between humans and chimps.
Edited by Admin, : Replace message numbers with message links.

This message is a reply to:
 Message 227 by Dr Adequate, posted 01-22-2017 1:36 AM Dr Adequate has replied

Replies to this message:
 Message 235 by Dr Adequate, posted 01-27-2017 12:24 PM CRR has replied

  
Dr Adequate
Member (Idle past 284 days)
Posts: 16113
Joined: 07-20-2006


Message 235 of 279 (797806)
01-27-2017 12:24 PM
Reply to: Message 234 by CRR
01-27-2017 3:33 AM


Re: The Maths
At Message 176 you posted a copy of sfs's post claiming that genetic drift could explain the difference between human and chimp genomes. At Message 195 you showed that you were talking about fixed mutations.
My argument was that taking mean time to fixity into account meant that less than half of the mutations could have been fixed in that time.
And how very wrong you were. (And if you were right it would hardly matter, this is an order-of-magnitude calculation.)
At Message 203 you presented what appeared to be the same argument from a different perspective.
It was not the same argument, nor did it seem to be so, since I explicitly said I was calculating something else.
Can you find an error in the calculation?
You are going to have to do a lot more to show that genetic drift is a plausible explanation for the genetic difference between humans and chimps.
Perhaps to show you that I would have to perform an actual miracle. Geneticists, on the other hand, consider the thing to be proven.

This message is a reply to:
 Message 234 by CRR, posted 01-27-2017 3:33 AM CRR has replied

Replies to this message:
 Message 236 by CRR, posted 01-31-2017 2:48 AM Dr Adequate has replied

  
CRR
Member (Idle past 2242 days)
Posts: 579
From: Australia
Joined: 10-19-2016


Message 236 of 279 (798109)
01-31-2017 2:48 AM
Reply to: Message 235 by Dr Adequate
01-27-2017 12:24 PM


Re: The Maths
Well perhaps you will have to explain it again so that even I can understand it.

This message is a reply to:
 Message 235 by Dr Adequate, posted 01-27-2017 12:24 PM Dr Adequate has replied

Replies to this message:
 Message 237 by Pressie, posted 01-31-2017 7:12 AM CRR has not replied
 Message 238 by Dr Adequate, posted 01-31-2017 9:42 AM CRR has replied

  
Pressie
Member
Posts: 2103
From: Pretoria, SA
Joined: 06-18-2010


Message 237 of 279 (798116)
01-31-2017 7:12 AM
Reply to: Message 236 by CRR
01-31-2017 2:48 AM


Re: The Maths
Or, maybe you need to get some degree in genetics to learn how to understand the basics?

This message is a reply to:
 Message 236 by CRR, posted 01-31-2017 2:48 AM CRR has not replied

  
Dr Adequate
Member (Idle past 284 days)
Posts: 16113
Joined: 07-20-2006


(1)
Message 238 of 279 (798135)
01-31-2017 9:42 AM
Reply to: Message 236 by CRR
01-31-2017 2:48 AM


Re: The Maths
Well perhaps you will have to explain it again so that even I can understand it.
Hmph. I'm not sure there is a simpler way to put it. I'll explain it again, and you point out where you stop understanding me.
First, bear in mind that what we're doing here is getting a ballpark figure of the genetic distance between one human and one chimpanzee. It is not going to be an exact figure, for reasons I will explain at the end, nor are we calculating the fixations that differentiate the populations as wholes.
So, I have μ mutations that my parents didn't have.
My parents in turn each have μ mutations that my grandparents didn't have. I inherit half of each of these, and I have two parents, so my parents contribute μ + μ = μ mutations to my inheritance: put that together with my own mutations, and I have 2μ mutations that my grandparents didn't have.
My grandparents in turn each have μ mutations that my great-grandparents didn't have. I inherit a quarter of each of these, and I have four grandparents, so my grandparents contribute μ + μ + μ + μ = μ mutations to my inheritance: put that together with my own mutations and the ones I got from my parents, and I have 3μ mutations that my great-grandparents didn't have.
And so on. It follows that if there have been G generations since the chimp-human split, I have accumulated μG mutations, and so will any given chimp. The difference between us will be 2μG.
This is an underestimate. Why? Because it doesn't take into account the diversity which existed before the split, which will have been lost in different ways on the way to me and the chimp. (Usually this will involve fixation in the two populations as a whole. )
But we're not striving for great accuracy. A ballpark figure would do for now. That figure is clearly of the same order of magnitude as the differences that actually exist.

This message is a reply to:
 Message 236 by CRR, posted 01-31-2017 2:48 AM CRR has replied

Replies to this message:
 Message 239 by RAZD, posted 01-31-2017 10:09 AM Dr Adequate has replied
 Message 241 by CRR, posted 02-01-2017 6:34 AM Dr Adequate has replied

  
RAZD
Member (Idle past 1405 days)
Posts: 20714
From: the other end of the sidewalk
Joined: 03-14-2004


Message 239 of 279 (798139)
01-31-2017 10:09 AM
Reply to: Message 238 by Dr Adequate
01-31-2017 9:42 AM


Re: The Maths
minor quibble
And so on. It follows that if there have been G generations since the chimp-human split, I have accumulated μG mutations, and so will any given chimp. The difference between us will be 2μG.
This assumes the same number of generations in humans and chimps. Chimps are fertile sooner and don't live as long as humans, while many humans delay reproduction, so I would expect them to have more generations ... now. They would have started out with the same generation length at the time of the split.
On the flip side though, I expect selection pressure was higher for humans due to changing their environments, chimps likely selected more for stasis.
Shouldn't affect the ball-park however.

we are limited in our ability to understand
by our ability to understand
RebelAmerican☆Zen☯Deist
... to learn ... to think ... to live ... to laugh ...
to share.


Join the effort to solve medical problems, AIDS/HIV, Cancer and more with Team EvC! (click)

This message is a reply to:
 Message 238 by Dr Adequate, posted 01-31-2017 9:42 AM Dr Adequate has replied

Replies to this message:
 Message 240 by Dr Adequate, posted 01-31-2017 9:41 PM RAZD has seen this message but not replied

  
Dr Adequate
Member (Idle past 284 days)
Posts: 16113
Joined: 07-20-2006


(1)
Message 240 of 279 (798192)
01-31-2017 9:41 PM
Reply to: Message 239 by RAZD
01-31-2017 10:09 AM


Re: The Maths
This assumes the same number of generations in humans and chimps.
Yeah, when I said we're not striving for great accuracy, I meant it. Ballpark is all we're going to get.

This message is a reply to:
 Message 239 by RAZD, posted 01-31-2017 10:09 AM RAZD has seen this message but not replied

Replies to this message:
 Message 242 by CRR, posted 02-01-2017 6:35 AM Dr Adequate has not replied

  
Newer Topic | Older Topic
Jump to:


Copyright 2001-2023 by EvC Forum, All Rights Reserved

™ Version 4.2
Innovative software from Qwixotic © 2024