Annoying creationists

[krazyKemist]

[FONT=Times New Roman][SIZE=3]I see you mathematically challenged evolutionarians are still having difficulty understanding the mathematics of mutation and selection.

Will you please stop saying that ? Or must we start calling you biologically challenged ? Somebody who has no understanding, and no desire to understand biology ?

Really, mutation and selection of cancer cells are not an example of evolution? And who said that cancer cells were limited to point mutations? You are still missing the point that cancer cells subjected to combination therapies have a more difficult time evolving resistance to these combination therapies despite all the forms of genetic alterations that you mention. I have a citation below which equates treatment of cancer and malaria with combination therapies as analogous examples of evolution of drug resistance. You really are slow in understanding the mathematics of mutation and selection.

You seem to confuse "adaptation", "evolution" and "point mutation". I wrote :

Point mutations do not explain how cancer cells adapt to chemo agents to a significant extent.

Did you miss the very pertinent example I gave in my previous post about carbonic anhydrase IX ? A gene normally expressed during embryo stage which gets reactivated in solid tumors under hypoxia ? If the genes needed to adapt to chemo agents are already present, unexpressed, ie do not need to be created de novo by point mutation, in tumor cells, how does ev explain cancer cell resistance to chemo ? Isn't ev about adaptation, using only point mutations ? How can it be pertinent then to cancer therapy ?

And if, as you pretend, ev is pertinent to cancer therapy, how does it explain the less than 100% success of multiple drug chemotherapy ? Especially in cases where more than 8 agents are combined ? When your model says that over two selection pressures are sufficient to stop evolution ?

Hey krazyKemist, I haven’t asked this question about irreducible complexity of evolutionarians for a while, maybe you want to try to answer this? What were the components of the DNA replicase system doing before DNA could replicate? In particular, what were the function of helicase and gyrase?

This, Dr. Kleinman was answered satisfactorily for me by other posters, from things I have read myself in my curiosity about biology. Why would I need to repeat this if you insist on not understanding ? And why are you trying to switch subjects ? We were talking about cancer therapy ?

the Kemist

[Anacoluthon64]

Or must we start calling you biologically challenged ?Comprehensively challenged will do nicely.

'Luthon64

[Dr Adequate]

Will you please stop saying that ? Of course he won't. It's stupid, and it's a lie. He will recite it over and over until reality changes, which it won't.

In fact, as a latecomer to his thread, you may not have noticed that kleinman's admitted that much of what he posts is computer-generated. He's not so much saying it over and over again as repeatedly hitting the same button on his Lying Machine. This not only saves him time; it also spares him the humiliation of having to read what he writes and think about what it means.

For his own inability to cope with simple math, see the FAQ linked to in my sig ... enjoy!

[krazyKemist]

Of course he won't. It's stupid, and it's a lie. He will recite it over and over until reality changes, which it won't.

In fact, as a latecomer to his thread, you may not have noticed that kleinman's admitted that much of what he posts is computer-generated. He's not so much saying it over and over again as repeatedly hitting the same button on his Lying Machine. This not only saves him time; it also spares him the humiliation of having to read what he writes and think about what it means.

For his own inability to cope with simple math, see the FAQ linked to in my sig ... enjoy!

In fact, I read far back enough to see that particular post about copy-pasting. I'm a pretty naive person, I guess :o (Hey, I always maintained that Snape was good, goes to show...:D ).

And I read the FAQ also, which gave me a couple giggles, and made me realize that the program I use for molecular docking is actually a more complicated version of ev, in which recombination and crossing-over are allowed. And that a fitness landscape is very similar to a potential energy landscape. Finding an energy minima in binding an enzyme is also a sorting and optimisation problem. In this program, the genetic algorithm is very efficient despite more than 20 constraints...

the Kemist

[kleinman]

I think the theory of evolution should be renamed to the theory of convolution. This ridiculous theory is so twisted maybe we should call it the theory of pretzelution, or how about the theory of speculation? Consider the following posts.
What relevance does your silly question have to how mutation and selection actually works?It's relevent to impeach your credibility. It shows you have a bias to misrepresent the facts. It's relevent to prove that you are not competent as an expert on the subject of evolution, or on any scientific subject matter, because your underlying dogma is that magic (the creation of something from nothing -- which violates all physical properties of the known universe) is the only truth.

Thus, the question is the most relevant of all questions that could possibly be asked in this thread.
So let’s again consider lita’ gators strange twisted and speculative question whether it has anything to do with the mathematics and empirical behavior of mutation and selection.
Were we able to observe the moments immediately surrounding and including the birth of a new species, what exactly would we see?
So lita’ gator wants me to speculate about the birth of a new species, why should I do this when we have empirical evidence how mutation and selection actually works. If lita’ gator has an example evolution accelerating with combination selection pressures, let him present his evidence. In the meantime, I will leave the speculation to the masters of the art, you hyperspeculating evolutionarians.
I see you mathematically challenged evolutionarians are still having difficulty understanding the mathematics of mutation and selection.Well, yeah, since you haven't shown any mathematics to prove it.
Perhaps you are not aware that Paul Anagnostopoulos, a moderator of the James Randi educational forum has written the java, online version of Dr Schneider’s ev computer simulation of random point mutation and natural selection. Hundreds of cases from this model have been posted on this thread as well as the related thread on the Evolutionisdead forum. Now if you are interested in learning how mutation and selection actually works mathematically, you can either study the data that Paul, Myriad and I have posted in the past year or run the model yourself and study the data and mathematics of mutation and selection that way. In the meantime, get a note from your mother explaining why you have come late and have not done your homework.
I see you mathematically challenged creationists are still having difficulty understanding the mathematics of mutation and selection. Since Alan has gone into denial about what Paul's mathematical model was never designed to show, he will continue to post pointless examples of how mutation and selection doesn't work.
Why pussycat, how could you get such an idea? Didn’t you read Dr Schneider’s peer reviewed and published paper where he said the following?
Variations of the program could be used to investigate how population size, genome length, number of sites, size of recognition regions, mutation rate, selective pressure, overlapping sites and other factors affect the evolution.
So you make several errors in your post, let’s start with your statement that its Paul’s mathematical model, you are wrong. The model was written by Dr Tom Schneider, the head of computational molecular biology at the National Cancer Institute. Second, it was Dr Schneider’s intention that the model be used to investigate the very features that are being discussed in this thread. Third, the citations I have and will continue to post demonstrate empirically exactly what Dr Schneider’s model shows mathematically, that is combination selection pressures is what slows down the evolutionary process and is the dominant parameter in his model. Now, whether I am a mathematically challenged creationist, perhaps you want to join Adequate’s camp and show us an example of multiple selection pressures accelerating evolution? Pussycat, I think you have been at the catnip a bit too much.
You've got nothing?
Nothing but a peer reviewed an published model of random point mutation and natural selection which shows that combination selection pressures profoundly slow evolution and then I have posted about 100 citations which demonstrate this empirically and I have more citations, see below. Now if you want to have an example of nothing, consider this:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Nothing is the number of citations you have posted which demonstrates your silly contention in reality. You certainly are demonstrating elegance with all zero of your citations imaginary superhero, of course that elegance only exists in one of kjkent1’s 10^500 alternative universes.
I see you mathematically challenged evolutionarians are still having difficulty understanding the mathematics of mutation and selection.Will you please stop saying that ? Or must we start calling you biologically challenged ? Somebody who has no understanding, and no desire to understand biology ?
I think you should proudly wear your badge of mathematically challenged evolutionarian because that is what you are. Who cares what you call me if it isn’t true? So stop whining and admit you don’t understand the mathematics of mutation and selection. That is a prerequisite to being an evolutionarian.
Really, mutation and selection of cancer cells are not an example of evolution? And who said that cancer cells were limited to point mutations? You are still missing the point that cancer cells subjected to combination therapies have a more difficult time evolving resistance to these combination therapies despite all the forms of genetic alterations that you mention. I have a citation below which equates treatment of cancer and malaria with combination therapies as analogous examples of evolution of drug resistance. You really are slow in understanding the mathematics of mutation and selection. You seem to confuse "adaptation", "evolution" and "point mutation". I wrote :Point mutations do not explain how cancer cells adapt to chemo agents to a significant extent.
Oh, I am not confused about these terms, but you are confused about the mathematics of mutation and selection. Even though Dr Schneider’s model only addresses random point mutation and natural selection, it demonstrates the most important mathematical parameter in the mutation and selection process. That parameter is the number of selection conditions. The hundred or so citations which I have posted of real examples of mutation and selection are not limited to random point mutation and natural selection, any mechanism of genetic alteration can occur in these examples and yet each show that additional selection pressures slow the evolutionary process and that includes cancer cell evolution as well. So learn some mathematics of mutation and selection and understand how this process actually works.

Again, I will explain how the process of mutation and selection actually works in words for those of you who are mathematically challenged. Mutation and selection is a sorting process for beneficial and detriment mutation as the population attempts to evolve to the selection pressure. If the population is subjected to simultaneous selection pressures, it becomes much more difficult mathematically for the population to evolve to these simultaneous selection pressures. This is what is demonstrated in the ev computer simulation of random point mutations and natural selection. Empirically, other forms of mutations do not change this underlying mathematical finding. The number of selection pressures has a profound effect on a population’s ability to evolve to these selection pressures. This is what is demonstrated in the citations I have and will continue to post, see below. This type of mathematical behavior is seen in multiple areas of mathematics and science including system optimization, database sorting and iterative problem solving techniques.

So, here are more examples of how mutation and selection actually works.

http://www.bioline.org.br/request?jp06094 (http://www.bioline.org.br/request?jp06094)
The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereas chloroquine and sulfadoxine/pyrimethamine could once cure most infections, this is no longer true and requires examination of alternative regimens. Not all treatment failures are drug resistant and other issues such as expired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policy after drug resistance is established suppresses infections rather than curing them, leading to increased transmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs. Antifolate drug resistance (i.e. pyrimethamine) means that new combinations are urgently needed particularly because addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance to each having been documented soon after drug introduction. Drug combinations delay further transmission of resistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currently recommended drug combinations for falciparum malaria are variants of artemisinin combination therapy where a rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisinins used include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine, sulfadoxine/pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard of care must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only to the successful treatment of individual patients but also for public health control of malaria.
And
Combination chemotherapy′s principles remain the same whether one is treating cancer or malaria. Full doses of effective drugs in combination should be used to result in cure and to avoid the generation of drug-resistance. Combination chemotherapy for falciparum malaria is currently available and should be the standard of care. Artemisinin compounds (an alternative possibly being quinine) are combined with a variety of partners to include mefloquine, pyronaridine, piperaquine, amodiaquine, chlorproguanil-dapsone and lumefantrine. Actual treatment regimens are undergoing rapid evolution and so a list of updated websites is provided rather than a table of treatment regimens which will be superseded in the future.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1469-0691.2006.01492.x (http://www.blackwell-synergy.com/doi/abs/10.1111/j.1469-0691.2006.01492.x)
The emergence of mutations in nucleic acids is one of the major factors underlying evolution, providing the working material for natural selection. Most bacteria are haploid for the vast majority of their genes and, coupled with typically short generation times, this allows mutations to emerge and accumulate rapidly, and to effect significant phenotypic changes in what is perceived to be real-time. Not least among these phenotypic changes are those associated with antibiotic resistance. Mechanisms of horizontal gene spread among bacterial strains or species are often considered to be the main mediators of antibiotic resistance. However, mutational resistance has been invaluable in studies of bacterial genetics, and also has primary clinical importance in certain bacterial species, such as Mycobacterium tuberculosis and Helicobacter pylori, or when considering resistance to particular antibiotics, especially to synthetic agents such as fluoroquinolones and oxazolidinones. In addition, mutation is essential for the continued evolution of acquired resistance genes and has, e.g., given rise to over 100 variants of the TEM family of β-lactamases. Hypermutator strains of bacteria, which have mutations in genes affecting DNA repair and replication fidelity, have elevated mutation rates. Mutational resistance emerges de novo more readily in these hypermutable strains, and they also provide a suitable host background for the evolution of acquired resistance genes in vitro. In the clinical setting, hypermutator strains of Pseudomonas aeruginosa have been isolated from the lungs of cystic fibrosis patients, but a more general role for hypermutators in the emergence of clinically relevant antibiotic resistance in a wider variety of bacterial pathogens has not yet been proven.
It is these types of citations coupled with the mathematical results of ev which shows why the theory of evolution is mathematically impossible. Multiple selection pressures interfere with the evolutionary process. This is how mutation and selection works mathematically and this is how mutation and selection works empirically. The theory of evolution is mathematically impossible.

[Dr Adequate]

I think the theory of evolution should be renamed to the theory of convolution. This ridiculous theory is so twisted maybe we should call it the theory of pretzelution, or how about the theory of speculation? Consider the following posts.

So let’s again consider lita’ gators strange twisted and speculative question whether it has anything to do with the mathematics and empirical behavior of mutation and selection.

So lita’ gator wants me to speculate about the birth of a new species, why should I do this when we have empirical evidence how mutation and selection actually works. If lita’ gator has an example evolution accelerating with combination selection pressures, let him present his evidence. In the meantime, I will leave the speculation to the masters of the art, you hyperspeculating evolutionarians.

Perhaps you are not aware that Paul Anagnostopoulos, a moderator of the James Randi educational forum has written the java, online version of Dr Schneider’s ev computer simulation of random point mutation and natural selection. Hundreds of cases from this model have been posted on this thread as well as the related thread on the Evolutionisdead forum. Now if you are interested in learning how mutation and selection actually works mathematically, you can either study the data that Paul, Myriad and I have posted in the past year or run the model yourself and study the data and mathematics of mutation and selection that way. In the meantime, get a note from your mother explaining why you have come late and have not done your homework.

Why pussycat, how could you get such an idea? Didn’t you read Dr Schneider’s peer reviewed and published paper where he said the following?

So you make several errors in your post, let’s start with your statement that its Paul’s mathematical model, you are wrong. The model was written by Dr Tom Schneider, the head of computational molecular biology at the National Cancer Institute. Second, it was Dr Schneider’s intention that the model be used to investigate the very features that are being discussed in this thread. Third, the citations I have and will continue to post demonstrate empirically exactly what Dr Schneider’s model shows mathematically, that is combination selection pressures is what slows down the evolutionary process and is the dominant parameter in his model. Now, whether I am a mathematically challenged creationist, perhaps you want to join Adequate’s camp and show us an example of multiple selection pressures accelerating evolution? Pussycat, I think you have been at the catnip a bit too much.

Nothing but a peer reviewed an published model of random point mutation and natural selection which shows that combination selection pressures profoundly slow evolution and then I have posted about 100 citations which demonstrate this empirically and I have more citations, see below. Now if you want to have an example of nothing, consider this:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

Nothing is the number of citations you have posted which demonstrates your silly contention in reality. You certainly are demonstrating elegance with all zero of your citations imaginary superhero, of course that elegance only exists in one of kjkent1’s 10^500 alternative universes.

I think you should proudly wear your badge of mathematically challenged evolutionarian because that is what you are. Who cares what you call me if it isn’t true? So stop whining and admit you don’t understand the mathematics of mutation and selection. That is a prerequisite to being an evolutionarian.

Oh, I am not confused about these terms, but you are confused about the mathematics of mutation and selection. Even though Dr Schneider’s model only addresses random point mutation and natural selection, it demonstrates the most important mathematical parameter in the mutation and selection process. That parameter is the number of selection conditions. The hundred or so citations which I have posted of real examples of mutation and selection are not limited to random point mutation and natural selection, any mechanism of genetic alteration can occur in these examples and yet each show that additional selection pressures slow the evolutionary process and that includes cancer cell evolution as well. So learn some mathematics of mutation and selection and understand how this process actually works.

Again, I will explain how the process of mutation and selection actually works in words for those of you who are mathematically challenged. Mutation and selection is a sorting process for beneficial and detriment mutation as the population attempts to evolve to the selection pressure. If the population is subjected to simultaneous selection pressures, it becomes much more difficult mathematically for the population to evolve to these simultaneous selection pressures. This is what is demonstrated in the ev computer simulation of random point mutations and natural selection. Empirically, other forms of mutations do not change this underlying mathematical finding. The number of selection pressures has a profound effect on a population’s ability to evolve to these selection pressures. This is what is demonstrated in the citations I have and will continue to post, see below. This type of mathematical behavior is seen in multiple areas of mathematics and science including system optimization, database sorting and iterative problem solving techniques.

So, here are more examples of how mutation and selection actually works.

http://www.bioline.org.br/request?jp06094 (http://www.bioline.org.br/request?jp06094)

And


http://www.blackwell-synergy.com/doi/abs/10.1111/j.1469-0691.2006.01492.x (http://www.blackwell-synergy.com/doi/abs/10.1111/j.1469-0691.2006.01492.x)

It is these types of citations coupled with the mathematical results of ev which shows why the theory of evolution is mathematically impossible. Multiple selection pressures interfere with the evolutionary process. This is how mutation and selection works mathematically and this is how mutation and selection works empirically. The theory of evolution is mathematically impossible.

* sigh *

So, you haven't thought of any new lies, done any math, found any evidence for your fantasies, grasped how multiple drug therapies work, offered a critique of my computer model, offered a counterexample to my computer model, or even, it would seem, though up any new magic words. Even your pathetic little magical ritual with the little gif of the laughing dog is the same. I notice your animal totem didn't ward off reality this time, either.

You've got nothing?

For the love of Ed, at least think of a new lie so's we can all have a good giggle.

[kleinman]

* sigh *
Here is your silly allegation of how mutation and selection works:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
So Adequate, you better take a deep breath because the only thing you have proved in this thread is that you are incompetent in the mathematics of mutation and selection. Oh, you have proved something else; you have proved you are a whining crybaby who is easily annoyed by mathematical and empirical facts that contradict your belief system. So prepare yourself to be annoyed for a long time because my google search on this topic gives more than a million hits and we’ll pull you confused evolutionarians out of the morass of your brainwashed thinking of how mutation and selection works.

[Dr Adequate]

Here is your silly allegation of how mutation and selection works:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

So Adequate, you better take a deep breath because the only thing you have proved in this thread is that you are incompetent in the mathematics of mutation and selection. Oh, you have proved something else; you have proved you are a whining crybaby who is easily annoyed by mathematical and empirical facts that contradict your belief system. So prepare yourself to be annoyed for a long time because my google search on this topic gives more than a million hits and we’ll pull you confused evolutionarians out of the morass of your brainwashed thinking of how mutation and selection works. So, you have no critique of my model and no couterexample.

But you do have a cartoon of a dog. I guess that's as close as you can get.

For some reason you have attributed your crazy ravings about cheese to me. Whom do you hope to deceive by this?

[Belz...]

I think the theory of evolution should be renamed to the theory of convolution. This ridiculous theory is so twisted maybe we should call it the theory of pretzelution, or how about the theory of speculation? Consider the following posts.

Preaching. Get to the argument.

Perhaps you are not aware that Paul Anagnostopoulos, a moderator of the James Randi educational forum has written the java, online version of Dr Schneider’s ev computer simulation of random point mutation and natural selection.

I don't care how many different versions of this "ev" thing there is. You cannot arbitrarily pick ONE, simplistic computer simulation and decide that this applies to reality.

Simulation < Reality. Get it ?

Hundreds of cases from this model have been posted on this thread as well as the related thread on the Evolutionisdead forum.

Yeah, but since REAL cases trump simulations...

Now if you are interested in learning how mutation and selection actually works mathematically

No, I'm not, actually. I'm interested in learning how mutation and selection actuall work, period. But, be my guest. Prove it MATHEMATICALLY. Not by CLAIMING that a computer model proves it wrong, but by POSTING the mathematical equations that prove it.

Do YOUR homework.

[krazyKemist]

I think the theory of evolution should be renamed to the theory of convolution. This ridiculous theory is so twisted maybe we should call it the theory of pretzelution, or how about the theory of speculation? Consider the following posts.

So let’s again consider lita’ gators strange twisted and speculative question whether it has anything to do with the mathematics and empirical behavior of mutation and selection.

So lita’ gator wants me to speculate about the birth of a new species, why should I do this when we have empirical evidence how mutation and selection actually works. If lita’ gator has an example evolution accelerating with combination selection pressures, let him present his evidence. In the meantime, I will leave the speculation to the masters of the art, you hyperspeculating evolutionarians.

Perhaps you are not aware that Paul Anagnostopoulos, a moderator of the James Randi educational forum has written the java, online version of Dr Schneider’s ev computer simulation of random point mutation and natural selection. Hundreds of cases from this model have been posted on this thread as well as the related thread on the Evolutionisdead forum. Now if you are interested in learning how mutation and selection actually works mathematically, you can either study the data that Paul, Myriad and I have posted in the past year or run the model yourself and study the data and mathematics of mutation and selection that way. In the meantime, get a note from your mother explaining why you have come late and have not done your homework.

Why pussycat, how could you get such an idea? Didn’t you read Dr Schneider’s peer reviewed and published paper where he said the following?

So you make several errors in your post, let’s start with your statement that its Paul’s mathematical model, you are wrong. The model was written by Dr Tom Schneider, the head of computational molecular biology at the National Cancer Institute. Second, it was Dr Schneider’s intention that the model be used to investigate the very features that are being discussed in this thread. Third, the citations I have and will continue to post demonstrate empirically exactly what Dr Schneider’s model shows mathematically, that is combination selection pressures is what slows down the evolutionary process and is the dominant parameter in his model. Now, whether I am a mathematically challenged creationist, perhaps you want to join Adequate’s camp and show us an example of multiple selection pressures accelerating evolution? Pussycat, I think you have been at the catnip a bit too much.

Nothing but a peer reviewed an published model of random point mutation and natural selection which shows that combination selection pressures profoundly slow evolution and then I have posted about 100 citations which demonstrate this empirically and I have more citations, see below. Now if you want to have an example of nothing, consider this:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

Nothing is the number of citations you have posted which demonstrates your silly contention in reality. You certainly are demonstrating elegance with all zero of your citations imaginary superhero, of course that elegance only exists in one of kjkent1’s 10^500 alternative universes.

I think you should proudly wear your badge of mathematically challenged evolutionarian because that is what you are. Who cares what you call me if it isn’t true? So stop whining and admit you don’t understand the mathematics of mutation and selection. That is a prerequisite to being an evolutionarian.

Oh, I am not confused about these terms, but you are confused about the mathematics of mutation and selection. Even though Dr Schneider’s model only addresses random point mutation and natural selection, it demonstrates the most important mathematical parameter in the mutation and selection process. That parameter is the number of selection conditions. The hundred or so citations which I have posted of real examples of mutation and selection are not limited to random point mutation and natural selection, any mechanism of genetic alteration can occur in these examples and yet each show that additional selection pressures slow the evolutionary process and that includes cancer cell evolution as well. So learn some mathematics of mutation and selection and understand how this process actually works.

Again, I will explain how the process of mutation and selection actually works in words for those of you who are mathematically challenged. Mutation and selection is a sorting process for beneficial and detriment mutation as the population attempts to evolve to the selection pressure. If the population is subjected to simultaneous selection pressures, it becomes much more difficult mathematically for the population to evolve to these simultaneous selection pressures. This is what is demonstrated in the ev computer simulation of random point mutations and natural selection. Empirically, other forms of mutations do not change this underlying mathematical finding. The number of selection pressures has a profound effect on a population’s ability to evolve to these selection pressures. This is what is demonstrated in the citations I have and will continue to post, see below. This type of mathematical behavior is seen in multiple areas of mathematics and science including system optimization, database sorting and iterative problem solving techniques.

So, here are more examples of how mutation and selection actually works.

http://www.bioline.org.br/request?jp06094 (http://www.bioline.org.br/request?jp06094)

And


http://www.blackwell-synergy.com/doi/abs/10.1111/j.1469-0691.2006.01492.x (http://www.blackwell-synergy.com/doi/abs/10.1111/j.1469-0691.2006.01492.x)

It is these types of citations coupled with the mathematical results of ev which shows why the theory of evolution is mathematically impossible. Multiple selection pressures interfere with the evolutionary process. This is how mutation and selection works mathematically and this is how mutation and selection works empirically. The theory of evolution is mathematically impossible.

yawn... Scratching...

And if, as you pretend, ev is pertinent to cancer therapy, how does it explain the less than 100% success of multiple drug chemotherapy ? Especially in cases where more than 8 agents are combined ? When your model says that over two selection pressures are sufficient to stop evolution ?

Time for some cat pictures ?

the Kemist

[Dr Adequate]

I don't care how many different versions of this "ev" thing there is. You cannot arbitrarily pick ONE, simplistic computer simulation and decide that this applies to reality.

Simulation < Reality. Get it ?

Yeah, but since REAL cases trump simulations... Do bear in mind that kleinman is lying about what ev shows. See the FAQ for more details.

[Mr. Scott]

Dr. Kleinman, I think it would help you a lot to understand how the upright human spine evolved imperfectly from four-legged creatures. You don't want to find yourself in malpractice court again, do you? Here are a few links you should find helpful:

Walking Tall (quicktime movie included) (http://www.pbs.org/wgbh/evolution/library/07/1/l_071_02.html)

In those ancient creatures, as in modern quadrupeds, the spine functioned more like a flexible suspension bridge, supporting the body's organs -- a role to which it is structurally well suited. The human spine has been transformed into a weight bearing column, putting it under unprecedented stresses and dooming us to the likelihood of back injuries and pain.

Human Origin (http://home13.inet.tele.dk/palm/homweb.htm)

In order to counteract this handicap and to keep the centre of gravity over the feet they evolved a bend of their loins so that the slightly arched spine sloped in behind, giving the spine an S-shape, making the pelvis slope forward. Then they could keep the upper part of the body over the feet, and they needed not to walk with the knees bent. This made their upright manner of walking more comfortable, but the price was the weak loin that is a characteristic of man.

Development, medicine, and evolution of the neck and shoulder (http://pharyngula.org/index/weblog/comments/development_medicine_and_evolution_of_the_neck_and _shoulder/)

In addition to telling us something about evolution, the study also gives us hints to the root causes of some serious human pathologies..

The Evolution of Low Back Pain (http://www.naturaljointmobility.info/spine%20works%20handout.htm)

In the chimpanzee, the strength of the spine increases with flexion of the lowest joints. This is because the origins of the back muscles on the pelvis are above the lowest spinal joints. With the changed shape of the human pelvis, this situation is reversed. The origins of the back muscles are now below the lowest joints. To any engineer this is obviously an over-centre mechanism and the strength of the spine will be reduced to almost nothing by flexion. This would mean that the human spine could be broken like a chicken leg where it connects to the pelvis.

This additional link is provided for the amusement of evolutionists:

Why Intelligent Design Theory Improves Medical Research (http://www.csm.org.uk/news.php?viewmessage=44)

Times science correspondent Mark Henderson who claims that creationism leads to junk medicine

[Belz...]

Do bear in mind that kleinman is lying about what ev shows. See the FAQ for more details.

Time for an update, methinks.

[kleinman]

So, you have no critique of my model and no couterexample.
You presented a model? The only thing you presented was this:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Even though you have not presented a single example of your drawing, I have presented about 100 counterexamples (and I will present more). In addition, these counterexamples are based on the results obtained from Dr Schneider’s peer reviewed and published computer simulation of random point mutations and natural selection.
But you do have a cartoon of a dog. I guess that's as close as you can get.
Why Adequate, I co-opted that cartoon from you, don’t you remember? I like using your cartoon to emphasize how silly your drawing is. Perhaps someday you will apply your mathematical skills to mutation and selection and actually learn how this phenomenon works. Even if you want to discredit Dr Schneider’s work on ev (which you shouldn’t because he got his mathematics of the model correct), there is abundant empirical evidence that shows how ridiculous your assertions are that you make with your graph.
For some reason you have attributed your crazy ravings about cheese to me. Whom do you hope to deceive by this?
Perhaps it is because your mathematically impossible theory stinks like limburger and you are trying to revive your cadaverous theory with a nonsensical drawing. Perhaps somewhere in the past you exhibited some mathematical skills but it certainly is not showing on the mathematics of mutation and selection. Since you still don’t understand how mutation and selection works mathematically, let me show you how it works empirically.

The first article discusses the evolution of RNA viruses. These viruses have high mutation rates, high reproductive rates and short generation times, all features which the ev model shows are needed in order for evolution to occur with multiple selection pressures. In addition, these viruses have short genome lengths. These are all features which favor evolution.
http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.micro.51.1.151?cookieSet=1&journalCode=micro (http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.micro.51.1.151?cookieSet=1&journalCode=micro)
RNA viruses exploit all known mechanisms of genetic variation to ensure their survival. Distinctive features of RNA virus replication include high mutation rates, high yields, and short replication times. As a consequence, RNA viruses replicate as complex and dynamic mutant swarms, called viral quasispecies. Mutation rates at defined genomic sites are affected by the nucleotide sequence context on the template molecule as well as by environmental factors. In vitro hypermutation reactions offer a means to explore the functional sequence space of nucleic acids and proteins. The evolution of a viral quasispecies is extremely dependent on the population size of the virus that is involved in the infections. Repeated bottleneck events lead to average fitness losses, with viruses that harbor unusual, deleterious mutations. In contrast, large population passages result in rapid fitness gains, much larger than those so far scored for cellular organisms. Fitness gains in one environment often lead to fitness losses in an alternative environment. An important challenge in RNA virus evolution research is the assignment of phenotypic traits to specific mutations. Different constellations of mutations may be associated with a similar biological behavior. In addition, recent evidence suggests the existence of critical thresholds for the expression of phenotypic traits. Epidemiological as well as functional and structural studies suggest that RNA viruses can tolerate restricted types and numbers of mutations during any specific time point during their evolution. Viruses occupy only a tiny portion of their potential sequence space. Such limited tolerance to mutations may open new avenues for combating viral infections.
This second article shows why combination therapy against viruses is necessary to prevent the evolution of resistance.
http://qjmed.oxfordjournals.org/cgi/reprint/91/9/593.pdf (http://qjmed.oxfordjournals.org/cgi/reprint/91/9/593.pdf)
Attention needs to be focused on (a) the development of combination therapy for the prolonged inhibition of HBV replication without the emergence of resistance, and (b) improved protocols for the treatment of HCV-infected patients with advanced disease and unfavourable virological characteristics.
See Adequate; take the data from the model you believe represents the real world and present empirical examples. It’s really very simple (if the model you are using represents reality). The reason why you can’t present any real examples of your graph is that your graph doesn’t represent reality of course; neither does the theory of evolution. Mutation and selection doesn’t work that way.
Reptiles turn into birds?
http://forums.randi.org/images/smilies/doglaugh.gif
Life arose in the primordial soup?
http://forums.randi.org/images/smilies/doglaugh.gif
You evolutionarians really like your mythology. This is what happens when the field of biology meets the SciFi channel. Too bad the mathematical and empirical evidence refutes your nonsense.

[kjkent1]

Were we able to observe the moments immediately surrounding and including the birth of a new species, what exactly would we see?So lita’ gator wants me to speculate about the birth of a new species, why should I do this when we have empirical evidence how mutation and selection actually works.Because, if your assertion is that evolution is impossible, then you must be prepared to explain how it is that the millions of varied life forms came to be -- including those which are now extinct, and those new forms which from time to time are discovered.

If your answer is "Genesis 1:1," then you are not a scientist, because you reject not only evolution, but also every other scientific principle of the universe.

Something from nothing is impossible. If you contend that God occasionally sticks his magic finger into the universe and creates a new species, then you need to explain how this is accomplished without leaving any energy trail.

I suggest that the instantaneous creation of a new species would require a very large amount of energy. Furthermore, God's appearance in this universe as a predicate to creating a new species (if that's how He does it), would also require a large amount of energy.

I'm no physicist, but I'll bet the energy required would likely be enough to vaporize a substantial portion of our planet.

So, Alan, if you expect to be taken seriously, then explain how God accomplishes the instantaneous creation of new species, without benefit of evolutionary theory.

If you can't, then Occam's razor takes effect, and despite your best efforts, evolution wins, because it's not just the simplest alternative explanation of how life for variation came to be -- it's the ONLY explanation.

[kleinman]

Were we able to observe the moments immediately surrounding and including the birth of a new species, what exactly would we see?So lita’ gator wants me to speculate about the birth of a new species, why should I do this when we have empirical evidence how mutation and selection actually works.Because, if your assertion is that evolution is impossible, then you must be prepared to explain how it is that the millions of varied life forms came to be -- including those which are now extinct, and those new forms which from time to time are discovered.
Really, you evolutionarians are still are having trouble understanding how mutation and selection actually works. When you acknowledge the mathematical and empirical facts of how mutation and selection actually works and that it makes your theory of evolution to be impossible then we can continue our discussions further. As it stands, the presuppositions that evolutionarians hold on to prevent them from understanding the mathematics and supporting empirical evidence of how mutation and selection actually works. Evolutionarian programming interferes with a proper understanding of how mutation and selection works in reality. We’ll continue to work on the phenomenon of mutation and selection until you evolutionarians finally understand how it actually works then we can go on to other topics. We don’t want to move the goalposts, do we?

[Dr Adequate]

You presented a model? The only thing you presented was this:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

Even though you have not presented a single example of your drawing, I have presented about 100 counterexamples. This is a new lie! Well done.

Of course, none of the experiments you've cited correspond in any way to the situation I'm modelling.

(and I will present more). In addition, these counterexamples are based on the results obtained from Dr Schneider’s peer reviewed and published computer simulation of random point mutations and natural selection.

Why Adequate, I co-opted that cartoon from you, don’t you remember? I like using your cartoon to emphasize how silly your drawing is. Perhaps someday you will apply your mathematical skills to mutation and selection and actually learn how this phenomenon works. Even if you want to discredit Dr Schneider’s work on ev (which you shouldn’t because he got his mathematics of the model correct), there is abundant empirical evidence that shows how ridiculous your assertions are that you make with your graph.

Perhaps it is because your mathematically impossible theory stinks like limburger and you are trying to revive your cadaverous theory with a nonsensical drawing. Perhaps somewhere in the past you exhibited some mathematical skills but it certainly is not showing on the mathematics of mutation and selection. Since you still don’t understand how mutation and selection works mathematically, let me show you how it works empirically.

The first article discusses the evolution of RNA viruses. These viruses have high mutation rates, high reproductive rates and short generation times, all features which the ev model shows are needed in order for evolution to occur with multiple selection pressures. In addition, these viruses have short genome lengths. These are all features which favor evolution.
http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.micro.51.1.151?cookieSet=1&journalCode=micro (http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.micro.51.1.151?cookieSet=1&journalCode=micro)

This second article shows why combination therapy against viruses is necessary to prevent the evolution of resistance.
http://qjmed.oxfordjournals.org/cgi/reprint/91/9/593.pdf (http://qjmed.oxfordjournals.org/cgi/reprint/91/9/593.pdf)

See Adequate; take the data from the model you believe represents the real world and present empirical examples. It’s really very simple (if the model you are using represents reality). The reason why you can’t present any real examples of your graph is that your graph doesn’t represent reality of course; neither does the theory of evolution. Mutation and selection doesn’t work that way.
Reptiles turn into birds?
http://forums.randi.org/images/smilies/doglaugh.gif
Life arose in the primordial soup?
http://forums.randi.org/images/smilies/doglaugh.gif
You evolutionarians really like your mythology. This is what happens when the field of biology meets the SciFi channel. Too bad the mathematical and empirical evidence refutes your nonsense. So, you've still got nothing except cartoons and insane gibberish about cheese.

[Dr Adequate]

Really, you evolutionarians are still are having trouble understanding how mutation and selection actually works. When you acknowledge the mathematical and empirical facts of how mutation and selection actually works and that it makes your theory of evolution to be impossible then we can continue our discussions further. As it stands, the presuppositions that evolutionarians hold on to prevent them from understanding the mathematics and supporting empirical evidence of how mutation and selection actually works. Evolutionarian programming interferes with a proper understanding of how mutation and selection works in reality. We’ll continue to work on the phenomenon of mutation and selection until you evolutionarians finally understand how it actually works then we can go on to other topics. We don’t want to move the goalposts, do we? What an interesting fantasy world you live in.

I was wondering, by the way --- what would you do if you thought that the gibberish you're reciting was actually true?

[kleinman]

What an interesting fantasy world you live in.
Your fantasy world is not so interesting. This is your fantasy:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
If infectious disease experts listened to your irrational nonsense they would use monotherapy to treat HIV, TB, HBV, HCV, Malaria,…, oncologists would use monotherapy to treat cancer, agriculture experts would use single herbicides to eliminate weeds…

Not only is your perception of reality wrong, if people were to listen to you, it would be destructive and harmful. Your fantasy world in not only uninteresting, it is wrong. Adequate, you are incompetent in the mathematics of mutation and selection. Every time you post on this thread and fail to give a real example of your silly graph, you demonstrate your incompetence.

[Dr Adequate]

Your fantasy world is not so interesting. This is your fantasy:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

If infectious disease experts listened to your irrational nonsense they would use monotherapy to treat HIV, TB, HBV, HCV, Malaria,…, oncologists would use monotherapy to treat cancer, agriculture experts would use single herbicides to eliminate weeds… What an exceptionally stupid lie.

Whom do you hope to deceive by telling it?


Not only is your perception of reality wrong, if people were to listen to you, it would be destructive and harmful. Your fantasy world in not only uninteresting, it is wrong. Adequate, you are incompetent in the mathematics of mutation and selection. Every time you post on this thread and fail to give a real example of your silly graph, you demonstrate your incompetence. So, you still have no criticism of my model and no counterexamples.

I notice that you are still attributing your idiotic garbage about cheese to me. We all know you're lying.

---

You still haven't answered my question --- what would you do if you thought you were telling the truth?

[kleinman]

So, you still have no criticism of my model and no counterexamples.
What model? Are you talking about your stupid and illogical graph? The one you have no real examples of. This is the incompetent mathematics you try to offer.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Here’s another counter example to your illogical fantasy.
http://www.nature.com/jid/journal/v85/n1/abs/5614578a.html (http://www.nature.com/jid/journal/v85/n1/abs/5614578a.html)
Endo B (melanotic) and W (amelanotic) human malignant melanomas originated from the same tumor, both known to be heterogeneous in drug sensitivity to ACNU([1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-cholethyl)-3-nitrosourea hydrochloride]), were treated experimentally with a combination therapy of ACNU and hyperthermia in mice. Whereas Endo W melanoma has no sensitivity, Endo B melanoma is sensitive to ACNU alone. However, in both types of melanomas, a marked synergistic effect of the combination therapy was noted. Histologically, marked degeneration of both tumor cells was detected. These results strongly suggest that thermochemotherapy may overcome the tumor heterogeneity in drug sensitivity.
Adequate, you better contact these authors and tell them that combination therapy is going to accelerate the evolution of resistance to their treatment.

Adequate, you really are the dimmest bulb of evolutionism posting on this thread; however I do enjoy annoying you with mathematical and empirical facts of how mutation and selection actually works. I’m enjoying posting counterexamples to your silly graph.

[Paul C. Anagnostopoulos]

Perhaps you are not aware that Paul Anagnostopoulos, a moderator of the James Randi educational forum has written the java, online version of Dr Schneider’s ev computer simulation of random point mutation and natural selection. Hundreds of cases from this model have been posted on this thread as well as the related thread on the Evolutionisdead forum. Now if you are interested in learning how mutation and selection actually works mathematically, you can either study the data that Paul, Myriad and I have posted in the past year or run the model yourself and study the data and mathematics of mutation and selection that way. In the meantime, get a note from your mother explaining why you have come late and have not done your homework.
Unfortunately, Ev does not model Kleinman's primary point of contention. It does not model cumulative application of simultaneous pressures. It can only model one or more pressures applied together. Furthermore, no one has ever run an Ev model that "stopped evolution," except when the Rcapacity problem was in play.

Or have I gotten behind the moving goalpost? Is that not Kleinman's current contention?

~~ Paul

[Belz...]

Reptiles turn into birds?

Strawman.

Life arose in the primordial soup

Armies of strawmen.

Really, you evolutionarians are still are having trouble understanding how mutation and selection actually works.

This from a guy who thinks a computer model trumps reality.

[Lamuella]

what's nice is that the thread is titled "annoying creationists" and does, indeed, feature an annoying creationist. Thank heavens for truth in advertising.

[Dr Adequate]

What model? Are you talking about your stupid and illogical graph? The one you have no real examples of. This is the incompetent mathematics you try to offer.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg


http://forums.randi.org/images/smilies/doglaugh.gif
So, you have no criticism of my model and no counterexamples.

Here’s another counter example to your illogical fantasy.
http://www.nature.com/jid/journal/v85/n1/abs/5614578a.html (http://www.nature.com/jid/journal/v85/n1/abs/5614578a.html)
This is not a counterexample to anything I have ever claimed.

Adequate, you better contact these authors and tell them that combination therapy is going to accelerate the evolution of resistance to their treatment. No matter how often you instruct me to tell halfwitted lies, I will not tell halfwitted lies, because I am not a halfwitted liar.


Adequate, you really are the dimmest bulb of evolutionism posting on this thread; however I do enjoy annoying you with mathematical and empirical facts of how mutation and selection actually works. I’m enjoying posting counterexamples to your silly graph. Of which you have none, you stupid liar.

---

I notice that you are still attributing your insane gibberish about cheese to me.

Everyone reading this thread knows that this is your lunatic babble, not mine.

What do you hope to gain by repeating this stupid lie?

[kleinman]

Perhaps you are not aware that Paul Anagnostopoulos, a moderator of the James Randi educational forum has written the java, online version of Dr Schneider’s ev computer simulation of random point mutation and natural selection. Hundreds of cases from this model have been posted on this thread as well as the related thread on the Evolutionisdead forum. Now if you are interested in learning how mutation and selection actually works mathematically, you can either study the data that Paul, Myriad and I have posted in the past year or run the model yourself and study the data and mathematics of mutation and selection that way. In the meantime, get a note from your mother explaining why you have come late and have not done your homework.Unfortunately, Ev does not model Kleinman's primary point of contention. It does not model cumulative application of simultaneous pressures. It can only model one or more pressures applied together. Furthermore, no one has ever run an Ev model that "stopped evolution," except when the Rcapacity problem was in play.
Oh really Paul, so when you put in the weight factors in your model for the selection conditions, was it an accident that you allowed the weight factors to be set equal to zero? It may not have been your intention to include this in the ev model, but it is in there and it demonstrates what happens if you reduce the number of selection conditions in the mutation and selection process. I understand that you are a biased evolutionarian and you and Dr Schneider intended to prove how evolution occurs mathematically and you have. Evolution is limited by the number of selection conditions imposed on the population and now you are trying to squirm out of this mathematical and empirical fact. But its too late Paul, the cat’s out of the bag and we now know how mutation and selection actually occurs because you inadvertently put that feature into the model. You are so cute when you squirm.

I’m sure you can convince your evolutionarian cohort that the primary purpose of ev is to show information can accumulate on a 256 base genome and that there were all kinds of 256 base replicants in the primordial soup but when you use longer genomes and reduce the number of selection conditions in the model then you see the actual behavior of mutation and selection. Ev models reality when you use realistic parameters in the model and it shows why the theory of evolution is mathematically impossible.

So tell us Paul, what were you trying to explain when you proposed your Rcapacity hypothesis? Weren’t you trying to explain why evolution ceased in the ev model? And what happens to evolution in the model when you reduce the number of selection conditions? I like hearing your squirmy answers to these questions.
Or have I gotten behind the moving goalpost? Is that not Kleinman's current contention?
Only in your dreams Paul will you argue away what ev shows by whining about moving goal posts. Ev shows exactly what happens in reality. Single selection conditions evolve far more rapidly then multiple selection condition. Of course, you can embrace Adequate’s silly hypothesis that multiple selection conditions accelerates evolution, but I’d rather see you try to squirm out of what your own mathematical model shows. But isn’t that the same thing?

You evolutionarians are really slow at learning the mathematics of mutation and selection, even when it’s your own model showing the results. Hey Paul, did I mention how much I like your work on the ev model? You really did a good job on it. You are a little confused on the results from the model but I have confidence that you will ultimately figure it out.

Dr Schneider may not be doing as much advertising of his ev model now but I’ll do my best to keep yours and his work in the limelight. It is such a good tool for understanding how mutation and selection actually works.
Really, you evolutionarians are still are having trouble understanding how mutation and selection actually works.This from a guy who thinks a computer model trumps reality.
Oh no Belz, I don’t think that a computer model trumps reality, I think that ev properly models reality and why is that, because ev shows that multiple selection pressures profoundly slows the evolutionary process. That effect is seen empirically as shown by the hundred or so citations that I have posted so far. Now in your mythological dream world of evolutionism you imagine multiple selection pressures accelerating evolution but the mathematical and empirical facts would contradict your fanciful thinking.

Belz, why don’t you embrace Adequate’s graph were he shows multiple selection pressures accelerating evolution and find a real example of this phenomenon and post this citation for us. That would make for an interesting debate.
what's nice is that the thread is titled "annoying creationists" and does, indeed, feature an annoying creationist. Thank heavens for truth in advertising.
I’m all for annoying evolutionarians with mathematical and empirical facts of how mutation and selection actually works. I particularly like doing this with an evolutionist written, peer reviewed and published model of random point mutation and natural selection. Paul, are you and Dr Schneider going to write any more mathematical models of mutation and selection, I really like your work; it is so annoyogenic to evolutionarians. Your interpretations of the results are flakey but I can correct these bizarre interpretations with empirical evidence.

[Mr. Scott]

Here’s another counter example to your illogical fantasy.
http://www.nature.com/jid/journal/v85/n1/abs/5614578a.html (http://www.nature.com/jid/journal/v85/n1/abs/5614578a.html)

Adequate, you better contact these authors and tell them that combination therapy is going to accelerate the evolution of resistance to their treatment.

I've read the abstract, and it doesn't seem to support your point, Kleinman. So, warming certain tumor cells makes a certain chemo more effective? Did I miss the meeting where synergy was discovered to be evidence of divine intervention?

On the other hand, I can see how one can make a shallow argument about combination therapy and intelligent design. For example, if I increase exercise, decrease eating, and change the types of food I eat, I will profoundly slow down and ultimately stop the evolution of my girth, prove the book of Genesis correct and Darwin wrong. Am I following you there, Alan?

I really don't think synergy is evidence for the supernatural.

Have a nice weekend.

[Dr Adequate]

Oh really Paul, so when you put in the weight factors in your model for the selection conditions, was it an accident that you allowed the weight factors to be set equal to zero? It may not have been your intention to include this in the ev model, but it is in there and it demonstrates what happens if you reduce the number of selection conditions in the mutation and selection process. I understand that you are a biased evolutionarian and you and Dr Schneider intended to prove how evolution occurs mathematically and you have. Evolution is limited by the number of selection conditions imposed on the population and now you are trying to squirm out of this mathematical and empirical fact. But its too late Paul, the cat’s out of the bag and we now know how mutation and selection actually occurs because you inadvertently put that feature into the model. You are so cute when you squirm.

I’m sure you can convince your evolutionarian cohort that the primary purpose of ev is to show information can accumulate on a 256 base genome and that there were all kinds of 256 base replicants in the primordial soup but when you use longer genomes and reduce the number of selection conditions in the model then you see the actual behavior of mutation and selection. Ev models reality when you use realistic parameters in the model and it shows why the theory of evolution is mathematically impossible.

So tell us Paul, what were you trying to explain when you proposed your Rcapacity hypothesis? Weren’t you trying to explain why evolution ceased in the ev model? And what happens to evolution in the model when you reduce the number of selection conditions? I like hearing your squirmy answers to these questions.

Only in your dreams Paul will you argue away what ev shows by whining about moving goal posts. Ev shows exactly what happens in reality. Single selection conditions evolve far more rapidly then multiple selection condition. Of course, you can embrace Adequate’s silly hypothesis that multiple selection conditions accelerates evolution, but I’d rather see you try to squirm out of what your own mathematical model shows. But isn’t that the same thing?

You evolutionarians are really slow at learning the mathematics of mutation and selection, even when it’s your own model showing the results. Hey Paul, did I mention how much I like your work on the ev model? You really did a good job on it. You are a little confused on the results from the model but I have confidence that you will ultimately figure it out.

Dr Schneider may not be doing as much advertising of his ev model now but I’ll do my best to keep yours and his work in the limelight. It is such a good tool for understanding how mutation and selection actually works.

Oh no Belz, I don’t think that a computer model trumps reality, I think that ev properly models reality and why is that, because ev shows that multiple selection pressures profoundly slows the evolutionary process. That effect is seen empirically as shown by the hundred or so citations that I have posted so far. Now in your mythological dream world of evolutionism you imagine multiple selection pressures accelerating evolution but the mathematical and empirical facts would contradict your fanciful thinking.

Belz, why don’t you embrace Adequate’s graph were he shows multiple selection pressures accelerating evolution and find a real example of this phenomenon and post this citation for us. That would make for an interesting debate.

I’m all for annoying evolutionarians with mathematical and empirical facts of how mutation and selection actually works. I particularly like doing this with an evolutionist written, peer reviewed and published model of random point mutation and natural selection. Paul, are you and Dr Schneider going to write any more mathematical models of mutation and selection, I really like your work; it is so annoyogenic to evolutionarians. Your interpretations of the results are flakey but I can correct these bizarre interpretations with empirical evidence. You've still got nothing?

That figures.

[fishbob]

Originally Posted by EV Evolution of Biological Information
Variations of the program could be used to investigate how population size, genome length, number of sites, size of recognition regions, mutation rate, selective pressure, overlapping sites and other factors affect the evolution.


. . . affect the evolution.
Looks like somebody cut off the rest of the sentence. That would be incredibly careless or quite credibly dishonest.

I wonder what the missing words before or after 'evolution' could be? Something to do with rates, mabye? Probably nothing to do with cheeze whiz.

[kleinman]

You've still got nothing?

That figures.
That’s right, we still have nothing from you except a silly graph, you remember the graph don’t you?
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
No real examples of your silly graph of mutation and selection. Now come on Adequate, give us a real example of your ridiculous graph, and stop being such a bore and continually demonstrating your mathematical incompetence.

[krazyKemist]

Dr. Kleinman, I think it would help you a lot to understand how the upright human spine evolved imperfectly from four-legged creatures. You don't want to find yourself in malpractice court again, do you? Here are a few links you should find helpful:

Walking Tall (quicktime movie included)


In those ancient creatures, as in modern quadrupeds, the spine functioned more like a flexible suspension bridge, supporting the body's organs -- a role to which it is structurally well suited. The human spine has been transformed into a weight bearing column, putting it under unprecedented stresses and dooming us to the likelihood of back injuries and pain.

Human Origin

In order to counteract this handicap and to keep the centre of gravity over the feet they evolved a bend of their loins so that the slightly arched spine sloped in behind, giving the spine an S-shape, making the pelvis slope forward. Then they could keep the upper part of the body over the feet, and they needed not to walk with the knees bent. This made their upright manner of walking more comfortable, but the price was the weak loin that is a characteristic of man.

Development, medicine, and evolution of the neck and shoulder

In addition to telling us something about evolution, the study also gives us hints to the root causes of some serious human pathologies..

The Evolution of Low Back Pain

In the chimpanzee, the strength of the spine increases with flexion of the lowest joints. This is because the origins of the back muscles on the pelvis are above the lowest spinal joints. With the changed shape of the human pelvis, this situation is reversed. The origins of the back muscles are now below the lowest joints. To any engineer this is obviously an over-centre mechanism and the strength of the spine will be reduced to almost nothing by flexion. This would mean that the human spine could be broken like a chicken leg where it connects to the pelvis.

I'd like to add a word: appendix !!!

Why did god make us all with appendixes, the stupid ?

the Kemist

[kleinman]

Why did god make us all with appendixes, the stupid ?
Why krazyKemist, I thought you were a mathematically challenged evolutionarian so you are off topic. Your question should be why did the appendix evolve? In fact, why not ask why anything evolved? Since you didn’t answer my Irreducible Complexity question about what the components of the DNA replicase system were doing before DNA could be replicated, here’s another question you evolutionarians can’t answer. The question is what is the selection pressure that would evolve a gene de novo? I’ll even phrase it this way, how do you select for something that doesn’t exist?

Feel free to claim there are a few gaps in the theory of evolution but there isn’t a gap in understanding how mutation and selection works mathematically. Ev shows that multiple selection pressures profoundly slow the evolutionary process and empirical evidence confirms this mathematical finding. Here is another example of the empirical evidence of this mathematical fact.

http://www.sciencemag.org/cgi/content/abstract/269/5224/696 (http://www.sciencemag.org/cgi/content/abstract/269/5224/696)
Combinations of antiretroviral drugs that prevent or delay the appearance of drug-resistant human immunodeficiency virus-type 1 (HIV-1) mutants are urgently required. Mutants resistant to 3'-azidothymidine (AZT, zidovudine) became phenotypically sensitive in vitro by mutation of residue 184 of viral reverse transcriptase to valine, which also induced resistance to (-)2'-deoxy-3'-thiacytidine (3TC). Furthermore, AZT-3TC coresistance was not observed during extensive in vitro selection with both drugs. In vivo AZT-3TC combination therapy resulted in a markedly greater decreased in serum HIV-1 RNA concentrations than treatment with AZT alone, even though valine-184 mutants rapidly emerged. Most samples assessed from the combination group remained AZT sensitive at 24 weeks of therapy, consistent with in vitro mutation studies.

[Dr Adequate]

That’s right, we still have nothing from you except a silly graph, you remember the graph don’t you?
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

No real examples of your silly graph of mutation and selection. Now come on Adequate, give us a real example of your ridiculous graph, and stop being such a bore and continually demonstrating your mathematical incompetence. So far as I know, no-one has done the experiment.

This is why I constructed a model. It's a scientist thing, you wouldn't understand.

Do you have a counterexample, or just a cartoon of a dog?

[Dr Adequate]

Why krazyKemist, I thought you were a mathematically challenged evolutionarian so you are off topic. Your question should be why did the appendix evolve? In fact, why not ask why anything evolved? Since you didn’t answer my Irreducible Complexity question about what the components of the DNA replicase system were doing before DNA could be replicated, here’s another question you evolutionarians can’t answer. The question is what is the selection pressure that would evolve a gene de novo? I’ll even phrase it this way, how do you select for something that doesn’t exist?

Feel free to claim there are a few gaps in the theory of evolution but there isn’t a gap in understanding how mutation and selection works mathematically. Ev shows that multiple selection pressures profoundly slow the evolutionary process and empirical evidence confirms this mathematical finding. Here is another example of the empirical evidence of this mathematical fact.

http://www.sciencemag.org/cgi/content/abstract/269/5224/696 (http://www.sciencemag.org/cgi/content/abstract/269/5224/696)
We all know you're lying, remember?

[cyborg]

For the folks watching at home half those 10,000 odd posts of Dr A.'s are just taken up with reminding us that every post kleinman makes is basically a lie.

[kleinman]

So far as I know, no-one has done the experiment.
Let’s make sure that everyone understands what experiment you are talking about:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
So you have come up with a graph that has no basis in reality and you are going to perform an experiment where multiple selection pressures accelerate evolution. So tell us Adequate, what elegant experiment you would propose. Name a couple of selection pressures you can dredge up from your evolutionarian programmed mind that would perform like this? If you had any understanding of how mutation and selection actually works, you would know that mutation and selection is a sorting phenomenon. So imaginary superhero of amathematics; name any mathematical sorting problem that converges more rapidly the greater the number of sorting conditions imposed. Perhaps you want to apply the law of large numbers, when you have an infinite number of selection conditions your model converges in a single generation?
http://forums.randi.org/images/smilies/doglaugh.gif

Here are a couple more citations for you mathematically challenged evolutionarians to ponder over the weekend. The first citation shows explicitly that use of sequential therapy of HIV quickly leads to resistance when compared to simultaneous combination therapy.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24062 (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24062)
Exposure to 3TC of HIV-1 mutant strains containing non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific mutations in their reverse transcriptase (RT) easily selected for double-mutant viruses that had acquired the characteristic 184-Ile mutation in their RT in addition to the NNRTI-specific mutations. Conversely, exposure of 3TC-resistant 184-Val mutant HIV-1 strains to nine different NNRTIs resulted in the rapid emergence of NNRTI-resistant virus strains at a time that was not more delayed than when wild-type HIV-1(IIIB) was exposed to the same compounds. The RTs of these resistant virus strains had acquired the NNRTI-characteristic mutations in addition to the preexisting 184-Val mutation. Surprisingly, when the 184-Ile mutant HIV-1 was exposed to a variety of NNRTIs, the 188-His mutation invariably occurred concomitantly with the 184-Ile mutation in the HIV-1 RT. Breakthrough of this double-mutant virus was markedly accelerated as compared with the mutant virus selected from the wild-type or 184-Val mutant HIV-1 strain. The double (184-Ile + 188-His) mutant virus showed a much more profound resistance profile against the NNRTIs than the 188-His HIV-1 mutant. In contrast with the sequential chemotherapy, concomitant combination treatment of HIV-1-infected cells with 3TC and a variety of NNRTIs resulted in a dramatic delay of virus breakthrough and resistance development.
This citation shows that monotherapy done sequentially quickly leads to resistance to both drugs while combination therapy of HBV slows the evolution of resistance.
http://www.journals.uchicago.edu/cgi-bin/resolve?JID990624PDF (http://www.journals.uchicago.edu/cgi-bin/resolve?JID990624PDF)
Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load 11 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.
And
Our study demonstrates that dual combination therapy with lamivudine and famciclovir after failure of lamivudine monotherapy is ineffective at suppressing HBV replication in chronically infected patients, despite the presence of the M550I mutation. We show the complex quasispecies nature of HBV genotypes under drug-selection pressure and the difficulty in predicting drug susceptibility on the basis of the dominant virus species in serum. Lamivudine monotherapy appears to “prime” the rapid emergence of famciclovir resistance following addition of this second drug. We suggest that the risk of emergence of nucleoside-analogue resistance will be reduced by initial use of potent drug combinations, rather than sequential therapy, as has been illustrated for human immunodeficiency virus–infected patients [15]. Trials of such combinations are urgently required.
Again, citations which show that single selection pressures allow for rapid evolution of resistance while combination selection pressures slow the evolution of resistance. This is how mutation and selection actually works. Mutation and natural selection is a mathematically impossible mechanism for transforming a reptile into a bird. This is a fantasy that has come about in the mathematically challenged minds of evolutionarians.

Again, I review for the mathematically challenged why mutation and selection works this way. Mutation and selection is a sorting process for beneficial and detrimental mutations. This process occurs most rapidly when there is only a single selection pressure. If there are multiple simultaneous selection pressures, the process is profoundly slowed. This type of mathematical behavior is seen in many areas of science including system optimization, database sorting and iterative problem solving techniques. This is why Adequate can find no examples of his silly graph which shows that multiple selection pressures accelerate evolution. You evolutionarians really need to learn the mathematics of mutation and selection. It would help you understand why there are so many examples of mutation and selection where increasing the number of selection pressures slows the evolutionary process and there are no examples where multiple selection pressures accelerate evolution. You all have a good weekend and I hope your selection pressures are few.

[quixotecoyote]

Hey Dr. A, spare me from having to go through the last 125 pages hunting. Where did the data points for your graph come from?

[Dr Adequate]

Let’s make sure that everyone understands what experiment you are talking about:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif
So you have come up with a graph that has no basis in reality and you are going to perform an experiment where multiple selection pressures accelerate evolution. . I did not say that I was going to perform the experiment. You are a liar and a fool.

So tell us Adequate, what elegant experiment you would propose. Name a couple of selection pressures you can dredge up from your evolutionarian programmed mind that would perform like this? Any selection pressures whatsoever which fit the specification of my model.

If you had any understanding of how mutation and selection actually works, you would know that mutation and selection is a sorting phenomenon. So imaginary superhero of amathematics; name any mathematical sorting problem that converges more rapidly the greater the number of sorting conditions imposed. I have of course claimed no such thing, you stupid stinking drooling liar. And everyone can read the notes explaining what I am modelling, and see that you are a revolting lying turd.

As you can see, and as everyone can see from the graph, the time taken for convergence increases with the number of selection pressures. But the rate of fixations per generation also increases.

This is because in any sorting task, other things being equal, parallel processing is faster than serial processing.

When you try to pretend that I have claimed anything different, everyone can see what a retarded lying whining twat you are.

http://forums.randi.org/images/smilies/doglaugh.gif

Here are a couple more citations for you mathematically challenged evolutionarians to ponder over the weekend. The first citation shows explicitly that use of sequential therapy of HIV quickly leads to resistance when compared to simultaneous combination therapy.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24062 (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24062)

This citation shows that monotherapy done sequentially quickly leads to resistance to both drugs while combination therapy of HBV slows the evolution of resistance.
http://www.journals.uchicago.edu/cgi-bin/resolve?JID990624PDF (http://www.journals.uchicago.edu/cgi-bin/resolve?JID990624PDF)

And

Again, citations which show that single selection pressures allow for rapid evolution of resistance while combination selection pressures slow the evolution of resistance. This is how mutation and selection actually works. Mutation and natural selection is a mathematically impossible mechanism for transforming a reptile into a bird. This is a fantasy that has come about in the mathematically challenged minds of evolutionarians.

Again, I review for the mathematically challenged why mutation and selection works this way. Mutation and selection is a sorting process for beneficial and detrimental mutations. This process occurs most rapidly when there is only a single selection pressure. If there are multiple simultaneous selection pressures, the process is profoundly slowed. This type of mathematical behavior is seen in many areas of science including system optimization, database sorting and iterative problem solving techniques. This is why Adequate can find no examples of his silly graph which shows that multiple selection pressures accelerate evolution. You evolutionarians really need to learn the mathematics of mutation and selection. It would help you understand why there are so many examples of mutation and selection where increasing the number of selection pressures slows the evolutionary process and there are no examples where multiple selection pressures accelerate evolution. You all have a good weekend and I hope your selection pressures are few. So, you've still got nothing?

[Dr Adequate]

Hey Dr. A, spare me from having to go through the last 125 pages hunting. Where did the data points for your graph come from? The essence of it is in the routine below. This gives one run through from a starting position where none of the beneficial mutations have occurred, to the point at which they're all fixed.

To produce the nice smooth curves on the graph, I ran it thousands of times and averaged them.

---

function t(selected: integer; genes: integer): integer;

var genome: array[0 .. 1, 1 .. pop, 1 .. 10] of boolean;
fitness: array[0 .. 1, 1 .. pop] of real;
c, g, h, g1, g2, i, j, o, n, fixed, generations: integer;
flag: boolean;

begin

o:=0; n:=1;
for i:=1 to pop do for j:=1 to genes do genome[0,i,j]:=false;
for i:=1 to pop do fitness[0,i]:=1;

generations:=0;

repeat
c:=0;

repeat
c:=c+1;
g1:=1+random(pop);
g2:=1+random(pop);
if fitness[o,g1]*random > fitness[o,g2]*random then g:=g1 else g:=g2;
for j:=1 to genes do genome[n,c,j]:=genome[o,g,j];
fitness[n,c]:=fitness[o,g];
if random(50)=0 then
begin
j:=1+random(10);
genome[n,c,j]:=not(genome[n,c,j]);
if (genome[n,c,j]) and (j<=selected) then fitness[n,c]:=fitness[n,c]*1.25 else fitness[n,c]:=fitness[n,c]/1.25;
end;
until c=pop;

fixed:=0;
for j:=1 to selected do
begin
flag:=true;
for i:=1 to pop do flag:=flag and genome[n,i,j];
if flag then fixed:=fixed+1;
end;
if fixed=selected then
begin
selected:=selected+1;
if selected<=genes then
for i:=1 to pop do if genome[n,i,selected] then fitness[n,i]:=fitness[n,i]*1.25;
end;

o:=1-o; n:=1-n;
generations:=generations+1;

until (fixed=genes);

t:=generations;

end;

---

Notes:

* If you call this function with parameters (1,n) then this gives you sequential selection pressures; call it with (n,n) and they're simultaneous.

* The genetic code is taken to be binary, for convenience in coding.

* The method of selection is that two genomes are chosen at random, and then they battle it out one-on-one to reproduce based on their fitness. This, I have found, is a good, computationally fast way of ensuring that the relative fitness is what you think it is.

[cyborg]

That is Pascal I assume?

[Dr Adequate]

That is Pascal I assume? Yes.

* eats quiche *

[Belz...]

Oh no Belz, I don’t think that a computer model trumps reality, I think that ev properly models reality

Yes, and that is EXACTLY why I said that you think it trumps reality: you have forgotten, ignored or otherwise hand-waved the fact that the model does not represent reality. It only models a few factors, so even if it were accurate, which also seems to be in dispute, you'd still lack the other factors necessary to make the determination you seem so adamant to stick to.

and why is that, because ev shows that multiple selection pressures profoundly slows the evolutionary process

Let me get this straight. You think that ev properly models reality because it agrees with a preconceived notion of yours ? Are you saying that, if ev showed the opposite, you'd think it DIDN'T model reality properly ?

That effect is seen empirically as shown by the hundred or so citations that I have posted so far.

You also said "mathematically", but I'm yet to see a single equation.

Now in your mythological dream world of evolutionism you imagine multiple selection pressures accelerating evolution

Klein, your attitude is despicable. Start arguing like an adult.

but the mathematical and empirical facts would contradict your fanciful thinking.

"Mathematical fact" ?

[Belz...]

Your question should be why did the appendix evolve?

A simple look at a scientific website will answer that question. The fact that you admit not to know the answer shows that you are not serious in your search.

By all means, tell us in your great wisdom why Gunderscored created the appendix.

[Anacoluthon64]

Time for an update, methinks.Dr A, if you intend updating the FAQ as suggested, you might consider including the following where you write thus:The mistake Kleinman has made, or one of them, is to take a realistic value for p (the probability of a point mutation for a given base) but not for n (the population). This gives a totally unrealistic value for the probability that a given substition will occur in the gene pool per generation, which is given by:

q = 1 - (1 - p/3)n

If, for example, we take a realistic value for p of 10-8, then for a measly million organisms, q is 0.3%. For a lousy billion, it's 96.4%.

If we use a more realistic order of magnitude for the bacteria, say something like the 1014 present in a single human gut, then my calculator isn't accurate enough to tell us the difference between q and 1.

…For the assumed values of p = 10-8 and n = 1014, the value of q is less than 1 by an amount smaller than 10–144,764. In other words, the probability that the substitution will not occur is less than 1:10144,764.

I'll be happy to provide you with the mathematics behind this should you so wish.

'Luthon64

[krazyKemist]

Why krazyKemist, I thought you were a mathematically challenged evolutionarian so you are off topic. Your question should be why did the appendix evolve? In fact, why not ask why anything evolved? Since you didn’t answer my Irreducible Complexity question about what the components of the DNA replicase system were doing before DNA could be replicated, here’s another question you evolutionarians can’t answer. The question is what is the selection pressure that would evolve a gene de novo? I’ll even phrase it this way, how do you select for something that doesn’t exist?

Dr. Kleinman, here's an example of a little ignorance on your part on the actual theory of evolution : see, the hypothesis is that the appendix is what is called a vestigial organ, that is something that was useful to our ancestors, and being quite useless or even harmful for us, as anybody who's had appendicitis could tell you. Trying to turn back this question to us is a quite clumsy attempt to shift the attention away. Now you will ask what evidence we have that the appendix was useful to our ancestors, right ?
And with this, you will ignore this simple, embarassing question : as an engineer, doesn't it strike you as pretty bad engineering if god actually made humans as they are (this is the creationist position, isn't it ?) ? Honestly ?

As for "Irreducible Complexity", I must admit it is one of the poorest argument ever designed by creationists, for anybody with a chemistry, biochemistry or molecular biology degree. Must we really talk about snowflakes, catalytic RNA, autoassembly of membranes, protein folding and crystal packing all over again ? I believe some of these were discussed earlier ?

And one of the funniest things is that creationists never discuss the most mysterious issue of all in abiogenesis, and it is not at all that simple molecules can form complex assemblies following natural laws. I can discuss it with you if you wish. It's pretty interesting and educative.

Feel free to claim there are a few gaps in the theory of evolution but there isn’t a gap in understanding how mutation and selection works mathematically. Ev shows that multiple selection pressures profoundly slow the evolutionary process and empirical evidence confirms this mathematical finding. Here is another example of the empirical evidence of this mathematical fact.

And here we go again... sigh... I, and other people here have explained to you, time and again, why ev doesn't model reality as it is:

- Assumption that point mutation is the only type of mutation
- Assumption that mutation of a gene affects one and only one gene, and one and only one aspect of the phenotype
- Assumption that transfer of genetic material (recombination, plasmids, naked DNA, viruses, ect.) between individuals is insignificant in the process of adaptation of a population at large
- Assumption that only one solution exists for a given problem (I can give you examples of that not being the case in biology, if you wish)
- And, of course, assumption that we know everything about the processes of life (and why are you so afraid of things you don't know ?)

All these things make ev a pretty bad model of reality as we know it. And now you will say that these assumptions are correct, right ? May I ask on what grounds ?

the Kemist

[Dr Adequate]

Your question should be why did the appendix evolve? Ah, the Argument from Undesign. No, you're right, nothing as dumb as the appendix could have evolved, so it must have been designed by a really, really stupid God.

[Dr Adequate]

All these things make ev a pretty bad model of reality as we know it. Do remember that he's lying about what ev shows, as the figures he himself has posted demonstrate.

Figures:

G=1000, mutation rate = 1 mutation per 1000 bases per generation, gamma = 16, binding site width = 6:
Population \ generation for convergence
2 \ failed to converge
4 , 66547
8 , 15916
16 , 17257
32 , 16416
64 , 9082
128 , 9378
256 , 4078
512 , 3685
1024 , 2793
2048 , 2080
4096 , 2565
6000 , 1541
8192 , 1798
16384 , 1001
32768 , 743
65536 , 633
131072 , 483
262144 , 702
524288 , 642
1048576 , 438

Lie:

ev demonstrates decreasing rates of convergence with increasing population.

Figures:

The following data from ev is based on a mutation rate of 1 mutation/256 bases/generation, G was varied, and the weight factors were set to 0 or 1 for the following series of cases. All other parameters were left at default values. The top row in the table gives the weight factors for missed binding sites, spurious binding sites in the gene and spurious binding sites outside the gene.

G \111 \110 \101 \011 \100 \010 \001
8192 \20237 \881 \22324 \20 \1 \13 \19
16384 \49963 \424 \41260 \20 \1 \21 \28
32768 \140958\436 \284,000+\20 \1 \9 \20

There are a couple of interesting numbers in this table highlighted in red. These two cases with two selection conditions actually took more generations to evolve than the three selection condition case.

Lie:

Ev shows that multiple selection pressures profoundly slow the evolutionary process.

[T'ai Chi]

..see, the hypothesis is that the appendix is what is called a vestigial organ, that is something that was useful to our ancestors, and being quite useless or even harmful for us, as anybody who's had appendicitis could tell you.


Anything can be harmful, that is not a good argument "krazyKemist". For example, I can accidently bite by cheek. Therefore teeth are harmful?

It is actually thought to have immune and other functions. See http://www.sciam.com/askexpert_question.cfm?articleID=000CAE56-7201-1C71-9EB7809EC588F2D7 to get educated and to quit yourself from using the sloppy argument in the future.

[Paul C. Anagnostopoulos]

Oh really Paul, so when you put in the weight factors in your model for the selection conditions, was it an accident that you allowed the weight factors to be set equal to zero?
Nope, not an accident. But notice how there is no capability for turning on the selection pressures sequentially and cumulatively. So we can either have them all on, or just two, or just one. Any comparative measure of the "speed of evolution" in these cases is irrelevant, since they are not evolving the same function. You keep singing the praises of the single pressure model in Ev without regard for the fact that you are comparing apples and oranges.


So tell us Paul, what were you trying to explain when you proposed your Rcapacity hypothesis? Weren’t you trying to explain why evolution ceased in the ev model?
We don't know if it ceased, because we never ran it long enough. It does slow down precipitously, because there are not enough bases in the binding sites to code a unique pattern. You were going to run some experiments where Rcapacity was not an issue yet the same sort of precipitous slowdown occured. You never ran those experiments. I ran some, and no precipitous slowdown occured.

This doesn't really matter, because you refuse to acknowledge that a binding site can be narrow enough to thwart the evolution of a unique pattern. That is the stoopid position you must take so that you can claim that we have seen evolution "stop" in Ev.

~~ Paul

[delphi_ote]

Anything can be harmful, that is not a good argument "krazyKemist". For example, I can accidently bite by cheek. Therefore teeth are harmful?
Kemist's argument is fine. Your argument is harmful to thinking people. We're talking about natural selection here. It selects for adaptations (which could potentially a very small chance of being slightly harmful) that increase the probability an organism will have offspring. Last time I checked, the ability to eat certainly falls into this category.

In the future, please remember that many people who post here are intelligent. Try to think before you post something this inane again.

[Dr Adequate]

Oh, by the way, I've been asked to update my FAQ; and I've kept copies of kleinman's stupidity to treasure over the years, every time he's told a particularly dumb lie; so I guess I can do that. Watch this space.

[Belz...]

Anything can be harmful, that is not a good argument "krazyKemist". For example, I can accidently bite by cheek. Therefore teeth are harmful?

Only if they do more harm than good, which is decidedly not usually the case.

[ksbluesfan]

Here's a new public forum in which you can annoy creationists.

http://www.parade.com/articles/editions/2007/edition_07-29-2007/Intelligence_Report

Pararde magazine is a 16 page "magazine" within many major US newspapers. This past Sunday, July 19, 2007, they ran this story:


The Creation Museum, which opened in May in Petersburg, Ky., certainly has created controversy. It offers a biblical alternative to mainstream views on geology, evolution and biology, yet the exhibits include fossils that, scientists say, provide evidence of being much older than the age of the Earth as determined by the Bible. And while fossils also indicate that dinosaurs became extinct more than 64 million years before man appeared, the museum’s 40-foot-high rooms feature animatronic dinos moving alongside early humans. The privately funded museum, designed by a former Universal Studios exhibit director, even depicts dinosaurs among the animals on Noah’s ark. Let us know what you think at Parade.com.


There is a poll that asks the question "Do you believe dinosaurs could have existed alongside early humans?" When I voted, 31% believed it was possible (woe to you USA). At the bottom of the page, you can read the comments of others or add your own comment (registration is required). There are some real gems in the comments, such as this one.

No scientific or historical fact in the Bible has ever been shown to be wrong. If you think not, better check a knowlegable source, not just your bias. Congrats to the AIG museum!

Have fun!

[kleinman]

I see you mathematically challenged evolutionarians are still having difficulty understanding the mathematics of mutation and selection. I can see that your brainwashing has been very thorough but I’ll continue to show you empirical data which shows that multiple selection pressures slows evolution profoundly.
Variations of the program could be used to investigate how population size, genome length, number of sites, size of recognition regions, mutation rate, selective pressure, overlapping sites and other factors affect the evolution. . . . affect the evolution.
Looks like somebody cut off the rest of the sentence. That would be incredibly careless or quite credibly dishonest.

I wonder what the missing words before or after 'evolution' could be? Something to do with rates, mabye? Probably nothing to do with cheeze whiz.
I almost missed this post. Fishbob is bobbing for fish stories. Now why don’t you get Dr Schneider’s paper a see if I cut something out? http://nar.oxfordjournals.org/cgi/content/full/28/14/2794 (http://nar.oxfordjournals.org/cgi/content/full/28/14/2794)
When you discover that I haven’t cut anything out, you can contact Dr Schneider at toms@ncifcrf.gov and whine about his grammar.
Hey Dr. A, spare me from having to go through the last 125 pages hunting. Where did the data points for your graph come from?
I can help you with that quixotecoyote, here’s were Adequate’s strange imaginations arose from his primordial soup.
http://forums.randi.org/showpost.php?p=2607145&postcount=4163 (http://forums.randi.org/showpost.php?p=2607145&postcount=4163)
Now Adequate finally will try to post some nonsense code.
function t(selected: integer; genes: integer): integer;

var genome: array[0 .. 1, 1 .. pop, 1 .. 10] of boolean;
fitness: array[0 .. 1, 1 .. pop] of real;
c, g, h, g1, g2, i, j, o, n, fixed, generations: integer;
flag: boolean;

begin

o:=0; n:=1;
for i:=1 to pop do for j:=1 to genes do genome[0,i,j]:=false;
for i:=1 to pop do fitness[0,i]:=1;

generations:=0;

repeat
c:=0;

repeat
c:=c+1;
g1:=1+random(pop);
g2:=1+random(pop);
if fitness[o,g1]*random > fitness[o,g2]*random then g:=g1 else g:=g2;
for j:=1 to genes do genome[n,c,j]:=genome[o,g,j];
fitness[n,c]:=fitness[o,g];
if random(50)=0 then
begin
j:=1+random(10);
genome[n,c,j]:=not(genome[n,c,j]);
if (genome[n,c,j]) and (j<=selected) then fitness[n,c]:=fitness[n,c]*1.25 else fitness[n,c]:=fitness[n,c]/1.25;
end;
until c=pop;

fixed:=0;
for j:=1 to selected do
begin
flag:=true;
for i:=1 to pop do flag:=flag and genome[n,i,j];
if flag then fixed:=fixed+1;
end;
if fixed=selected then
begin
selected:=selected+1;
if selected<=genes then
for i:=1 to pop do if genome[n,i,selected] then fitness[n,i]:=fitness[n,i]*1.25;
end;

o:=1-o; n:=1-n;
generations:=generations+1;

until (fixed=genes);

t:=generations;

end;
Adequate thinks he can fool people with this nonsense so let’s see what happens when we run this code fragment through a Pascal compiler.
In function `t':
pas:3: undeclared identifier `pop' (first use in this routine)
pas:3: (Each undeclared identifier is reported only once
pas:3: for each routine it appears in.)
pas:3: subrange bounds must be of ordinal type
pas:4: subrange bounds must be of ordinal type
pas:11: undeclared identifier `genome' (first use in this routine)
pas:12: undeclared identifier `fitness' (first use in this routine)
pas:56: syntax error at end of input
:dl:
The numbers above correspond to the line numbers in Adequate’s code fragment with errors in them. So not only is Adequate afraid to post his entire code, the code fragment he does post has syntax errors, he fails to describe what his selection conditions are. Adequate, you are completely wrong about how mutation and selection actually works and your error filled code fragment is proof of nothing other than you are incompetent in the mathematics of mutation and selection.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
:dl:
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
and why is that, because ev shows that multiple selection pressures profoundly slows the evolutionary processLet me get this straight. You think that ev properly models reality because it agrees with a preconceived notion of yours ? Are you saying that, if ev showed the opposite, you'd think it DIDN'T model reality properly ?
Oh no, I don’t believe that ev properly models mutation and selection properly because it agrees with a preconceived notion of mine. I believe that ev properly models mutation and selection because it agrees with the massive amount of empirical data available of real examples of mutation and selection. Examples cited already includes the evolution of HIV when subjected to multiple selection pressures, the evolution of HBV when subjected to multiple selection pressures, the evolution of HCV when subjected to multiple selection pressures, the evolution of Gonorrhea when subjected to single selection pressures, the evolution of MRSA when subjected to single selection pressures, the evolution of TB when subjected to single and multiple selection pressures, the evolution of Malaria with single and multiple selection pressures, the evolution of mosquito larvae when subjected to single and multiple selection pressures, the evolution of weeds when subjected to single and multiple selection pressures, the evolution of rodents when subjected to single and multiple selection pressures…

These numerous examples of mutation and selection which have been repeated over and over by many different scientists show exactly how mutation and selection works. Mutation and selection is a sorting process for beneficial and detrimental mutations. If you increase the number of selection conditions, this slows down the evolutionary process profoundly. This is what Dr Schneider’s ev program shows and this is what the empirical evidence of mutation and selection shows. Of course, feel free to post and example of multiple selection pressures accelerating evolution.
I'll be happy to provide you with the mathematics behind this should you so wish.
Why don’t you provide a real example where multiple selection pressures accelerating evolution? You evolutionarians also don’t understand how population affects the mathematics of mutation and selection. Study Dr Schneider’s ev program and see how population affects the rate of evolution.
Why krazyKemist, I thought you were a mathematically challenged evolutionarian so you are off topic. Your question should be why did the appendix evolve? In fact, why not ask why anything evolved? Since you didn’t answer my Irreducible Complexity question about what the components of the DNA replicase system were doing before DNA could be replicated, here’s another question you evolutionarians can’t answer. The question is what is the selection pressure that would evolve a gene de novo? I’ll even phrase it this way, how do you select for something that doesn’t exist?Dr. Kleinman, here's an example of a little ignorance on your part on the actual theory of evolution : see, the hypothesis is that the appendix is what is called a vestigial organ, that is something that was useful to our ancestors, and being quite useless or even harmful for us, as anybody who's had appendicitis could tell you. Trying to turn back this question to us is a quite clumsy attempt to shift the attention away. Now you will ask what evidence we have that the appendix was useful to our ancestors, right ? And with this, you will ignore this simple, embarassing question : as an engineer, doesn't it strike you as pretty bad engineering if god actually made humans as they are (this is the creationist position, isn't it ?) ? Honestly ?
So you don’t know what the function of the components of the DNA replicase system were before DNA could be replicated so you would rather talk about the appendix. You are more than a little ignorant of the mathematics of mutation and selection. You are totally ignorant of the mathematics of mutation and selection.
Oh really Paul, so when you put in the weight factors in your model for the selection conditions, was it an accident that you allowed the weight factors to be set equal to zero?Nope, not an accident. But notice how there is no capability for turning on the selection pressures sequentially and cumulatively. So we can either have them all on, or just two, or just one. Any comparative measure of the "speed of evolution" in these cases is irrelevant, since they are not evolving the same function. You keep singing the praises of the single pressure model in Ev without regard for the fact that you are comparing apples and oranges.
So what if your model doesn’t have the capabilities of turning on the selection pressures sequentially and cumulatively. Evolutionarians are already discrediting what the model shows so I’d rather post real examples of mutation and selection which reveals how the process actually works. I’ll leave it to you and Dr Schneider to put those features in your model if you are really interested in how mutation and selection actually works. Then maybe you can provide some real science to advance the treatment of cancer (after all, Dr Schneider does work for the National Cancer Institute). Sadly though, evolutionarians are more interested in advancing their belief system rather than treating cancer or HIV.
So tell us Paul, what were you trying to explain when you proposed your Rcapacity hypothesis? Weren’t you trying to explain why evolution ceased in the ev model?We don't know if it ceased, because we never ran it long enough. It does slow down precipitously, because there are not enough bases in the binding sites to code a unique pattern. You were going to run some experiments where Rcapacity was not an issue yet the same sort of precipitous slowdown occured. You never ran those experiments. I ran some, and no precipitous slowdown occured.
There is no such thing as your Rcapacity issue. Your model shows that each of the individual selection conditions easily can be satisfied in a tiny number of generations despite longer genome lengths. It is only when you try to run the model and satisfy all three selection conditions simultaneously that the program slows “precipitously”. This is exactly what happens as demonstrated by the numerous citations posted of real examples of mutation and selection.
This doesn't really matter, because you refuse to acknowledge that a binding site can be narrow enough to thwart the evolution of a unique pattern. That is the stoopid position you must take so that you can claim that we have seen evolution "stop" in Ev.
Paul, how far do you have to go into denial of what your own computer model reveals of the mathematics of mutation and selection? What your model shows is how difficult it becomes to sort detrimental and beneficial mutations as you lengthen the genome with three selection conditions. Reduce the number of selection conditions to one and your model can easily sort for the beneficial and detrimental mutation. That is the essential lesson of mutation and selection you learn from your model. It doesn’t matter whether you are evolving binding sites or any other sequence of bases. Your evolutionarian brainwashed and biased belief system is blocking you from understanding this simple lesson. I’ll continue to post real examples of this phenomenon for as many years as it takes until you understand this mathematical and real fact of how mutation and selection actually works.
Anything can be harmful, that is not a good argument "krazyKemist". For example, I can accidently bite by cheek. Therefore teeth are harmful?Kemist's argument is fine. Your argument is harmful to thinking people. We're talking about natural selection here. It selects for adaptations (which could potentially a very small chance of being slightly harmful) that increase the probability an organism will have offspring. Last time I checked, the ability to eat certainly falls into this category.
krazyKemist’s arguments are mathematically and empirically baseless when it comes to his discussion of mutation and selection so he tries to change the subject. Of course that is typical for evolutionarians. Since you evolutionarians refuse to understand the mathematics of mutation and selection, let’s give you more examples of how mutation and selection actually works, that is multiple selection pressures profoundly slow the evolutionary process.

http://www.medscape.com/viewarticle/521671_3 (http://www.medscape.com/viewarticle/521671_3)
A major goal of HAART is to suppress plasma HIV RNA below detectable levels by combining 3 or more antiretroviral agents from 1 or more classes. The use of agents from different classes lessens the development of resistance.[34] However, antiretroviral regimens containing drugs from more than 2 classes are not routinely recommended for patients who are treatment naive, because those in whom a 3-class regimen fails may become resistant to drugs in all 3 classes, leaving them with fewer options for subsequent therapy. A HAART regimen should have acceptable short- and long-term toxicity and must fit the patient's comorbidity profile and lifestyle.[35] Currently recommended initial HAART regimens specify the use of 2 NRTIs and either an NNRTI or a PI.[2]

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7538547&dopt=AbstractPlus (http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7538547&dopt=AbstractPlus)
L-697,661 is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase (RT) inhibitor. Its tolerability and activity in combination with zidovudine were evaluated in a 48-week double-blind study. One hundred nineteen zidovudine-naive HIV-1-infected patients with CD4 cell counts of 200-500/mm3 received either combination therapy, L-697,661 alone, or zidovudine alone. Activity was assessed by CD4 cell count changes. Selection for L-697,661-resistant virus was monitored by susceptibility testing of RT expressed by circulating viral RNA. Therapy was generally well tolerated. All groups receiving zidovudine exhibited transient increases in CD4 cell counts, while the L-697,661 monotherapy group showed a significant decline and yielded RT > 100-fold resistant to L-697,661 and associated with substitutions at RT residue 181. The RT from patients receiving combination therapy was maximally 15-fold less susceptible to L-697,661. Hence, cotreatment with zidovudine prevents selection of HIV-1 variants that are highly resistant to L-697,661 in patients naive to both compounds.
Again, these examples demonstrate how mutation and selection actually works. Combined selection pressures slow the evolutionary process. Some day you dim bulbs of evolutionism may understand this mathematical and empirical fact.


kleinman, it appears that you are simply cutting and pasting this information on a repetitive basis, this being the most recent example. In the future, simply include links to the posts containing your cites you wish to address. Then add whatever new commentary or information that you are attempting to present. (Reasonably short excerpts of previously posted information is fine; however, I do not want to see massive reproduction of information as you have done in this post. If you continue to simply reproduce your previous posts, you will be flooding the forum which may result in further actions.

[Dr Adequate]

I see you mathematically challenged evolutionarians are still having difficulty understanding the mathematics of mutation and selection. I can see that your brainwashing has been very thorough but I’ll continue to show you empirical data which shows that multiple selection pressures slows evolution profoundly.

I almost missed this post. Fishbob is bobbing for fish stories. Now why don’t you get Dr Schneider’s paper a see if I cut something out? http://nar.oxfordjournals.org/cgi/content/full/28/14/2794 (http://nar.oxfordjournals.org/cgi/content/full/28/14/2794)
When you discover that I haven’t cut anything out, you can contact Dr Schneider at toms@ncifcrf.gov (toms@ncifcrf.gov?subject=Tom%20Schneider's%20Home %20Page%20(index.html)) and whine about his grammar.

I can help you with that quixotecoyote, here’s were Adequate’s strange imaginations arose from his primordial soup.
http://forums.randi.org/showpost.php?p=2607145&postcount=4163 (http://forums.randi.org/showpost.php?p=2607145&postcount=4163)
Now Adequate finally will try to post some nonsense code.

Adequate thinks he can fool people with this nonsense so let’s see what happens when we run this code fragment through a Pascal compiler.

http://forums.randi.org/images/smilies/doglaugh.gif
The numbers above correspond to the line numbers in Adequate’s code fragment with errors in them. So not only is Adequate afraid to post his entire code, the code fragment he does post has syntax errors, he fails to describe what his selection conditions are. Adequate, you are completely wrong about how mutation and selection actually works and your error filled code fragment is proof of nothing other than you are incompetent in the mathematics of mutation and selection.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif


Oh no, I don’t believe that ev properly models mutation and selection properly because it agrees with a preconceived notion of mine. I believe that ev properly models mutation and selection because it agrees with the massive amount of empirical data available of real examples of mutation and selection. Examples cited already includes the evolution of HIV when subjected to multiple selection pressures, the evolution of HBV when subjected to multiple selection pressures, the evolution of HCV when subjected to multiple selection pressures, the evolution of Gonorrhea when subjected to single selection pressures, the evolution of MRSA when subjected to single selection pressures, the evolution of TB when subjected to single and multiple selection pressures, the evolution of Malaria with single and multiple selection pressures, the evolution of mosquito larvae when subjected to single and multiple selection pressures, the evolution of weeds when subjected to single and multiple selection pressures, the evolution of rodents when subjected to single and multiple selection pressures…

These numerous examples of mutation and selection which have been repeated over and over by many different scientists show exactly how mutation and selection works. Mutation and selection is a sorting process for beneficial and detrimental mutations. If you increase the number of selection conditions, this slows down the evolutionary process profoundly. This is what Dr Schneider’s ev program shows and this is what the empirical evidence of mutation and selection shows. Of course, feel free to post and example of multiple selection pressures accelerating evolution.

Why don’t you provide a real example where multiple selection pressures accelerating evolution? You evolutionarians also don’t understand how population affects the mathematics of mutation and selection. Study Dr Schneider’s ev program and see how population affects the rate of evolution.

So you don’t know what the function of the components of the DNA replicase system were before DNA could be replicated so you would rather talk about the appendix. You are more than a little ignorant of the mathematics of mutation and selection. You are totally ignorant of the mathematics of mutation and selection.

So what if your model doesn’t have the capabilities of turning on the selection pressures sequentially and cumulatively. Evolutionarians are already discrediting what the model shows so I’d rather post real examples of mutation and selection which reveals how the process actually works. I’ll leave it to you and Dr Schneider to put those features in your model if you are really interested in how mutation and selection actually works. Then maybe you can provide some real science to advance the treatment of cancer (after all, Dr Schneider does work for the National Cancer Institute). Sadly though, evolutionarians are more interested in advancing their belief system rather than treating cancer or HIV.

There is no such thing as your Rcapacity issue. Your model shows that each of the individual selection conditions easily can be satisfied in a tiny number of generations despite longer genome lengths. It is only when you try to run the model and satisfy all three selection conditions simultaneously that the program slows “precipitously”. This is exactly what happens as demonstrated by the numerous citations posted of real examples of mutation and selection.

Paul, how far do you have to go into denial of what your own computer model reveals of the mathematics of mutation and selection? What your model shows is how difficult it becomes to sort detrimental and beneficial mutations as you lengthen the genome with three selection conditions. Reduce the number of selection conditions to one and your model can easily sort for the beneficial and detrimental mutation. That is the essential lesson of mutation and selection you learn from your model. It doesn’t matter whether you are evolving binding sites or any other sequence of bases. Your evolutionarian brainwashed and biased belief system is blocking you from understanding this simple lesson. I’ll continue to post real examples of this phenomenon for as many years as it takes until you understand this mathematical and real fact of how mutation and selection actually works.

krazyKemist’s arguments are mathematically and empirically baseless when it comes to his discussion of mutation and selection so he tries to change the subject. Of course that is typical for evolutionarians. Since you evolutionarians refuse to understand the mathematics of mutation and selection, let’s give you more examples of how mutation and selection actually works, that is multiple selection pressures profoundly slow the evolutionary process.

http://www.medscape.com/viewarticle/521671_3 (http://www.medscape.com/viewarticle/521671_3)


http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7538547&dopt=AbstractPlus (http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7538547&dopt=AbstractPlus)

Again, these examples demonstrate how mutation and selection actually works. Combined selection pressures slow the evolutionary process. Some day you dim bulbs of evolutionism may understand this mathematical and empirical fact. Hello, moron?

You remember I said that population was constant?

So, hey, why don't you declare pop as a constant?

Is that too much for your tiny little mind?

Do try to bear in mind that I have a PhD in math, and a BSc in MCS, and have been programming computers since I was seven, whereas you, let's be fair, are an innumerate halfwit. Therefore, when you don't understand what I say, it's because I'm right and you're wrong.

Go and fix your stupid error, and see if you can then call the function.

I notice that you've told a couple of stupid lies about me: that I am "afraid" to post the entire code, and that I haven't said what the selection conditions are.

Why do you tell such stupid lies?

I've said what the rest of the code is: it calls the function thousands of times and averages the results. I am not "afraid" to show you how a for loop works, or how to take the average of a set of numbers, and if you ask me nicely, I shall do so. And the selection conditions are as I stated when I produced the graph, and as specified by the code. They're not a secret, you lying twat, they're right there in the code for everyone to read.

[kleinman]

I've said what the rest of the code is: it calls the function thousands of times and averages the results. I am not "afraid" to show you how a for loop works. And the selection are for the new mutations, as I have said: the precise details are given by the code.
Let’s review what Adequate is alleging.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
You’ve got no code which proves this and you’ve got no real examples of you’re nonexistent code. Mutation and selection simply does not work the way you allege and you’re tantrums will not make what you say to be true.

Adequate, let me show you again how to post a citation of how mutation and selection actually works.

http://links.jstor.org/sici?sici=0027-8424(19961112)93%3A23%3C13152%3ACCTFHI%3E2.0.CO%3B 2-D (http://links.jstor.org/sici?sici=0027-8424(19961112)93%3A23%3C13152%3ACCTFHI%3E2.0.CO%3B 2-D)
Exposure to 3TC of HIV-1 mutant strains containing non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific mutations in their reverse transcriptase (RT) easily selected for double-mutant viruses that had acquired the characteristic 184-Ile mutation in their RT in addition to the NNRTI-specific mutations. Conversely, exposure of 3TC-resistant 184-Val mutant HIV-1 strains to nine different NNRTIs resulted in the rapid emergence of NNRTI-resistant virus strains at a time that was not more delayed than when wild-type HIV-1 was exposed to the same compounds. The RTs of these resistant virus strains had acquired the NNRTI-characteristic mutations in addition to the preexisting 184-Val mutation. Surprisingly, when the 184-Ile mutant HIV-1 was exposed to a variety of NNRTIs, the 188-His mutation invariably occurred concomitantly with the 184-Ile mutation in the HIV-1 RT. Breakthrough of this double-mutant virus was markedly accelerated as compared with the mutant virus selected from the wild-type or 184-Val mutant HIV-1 strain. The double (184-Ile + 188-His) mutant virus showed a much more profound resistance profile against the NNRTIs than the 188-His HIV-1 mutant. In contrast with the sequential chemotherapy, concomitant combination treatment of HIV-1-infected cells with 3TC and a variety of NNRTIs resulted in a dramatic delay of virus breakthrough and resistance development.
See Adequate, you don’t have to throw a tantrum, just post an example of your ridiculous assertion, of course you can’t because mutation and selection doesn’t work that way. Evolution by mutation and selection is slowed (dramatically as the above citation shows) by increasing the number of selection conditions; it is not accelerated as you so irrationally speculate. Adequate, you really are incompetent in the mathematics of mutation and selection. What did you get your PhD in? Was that amathematics?

[Paul C. Anagnostopoulos]

There is no such thing as your Rcapacity issue. Your model shows that each of the individual selection conditions easily can be satisfied in a tiny number of generations despite longer genome lengths. It is only when you try to run the model and satisfy all three selection conditions simultaneously that the program slows “precipitously”.
Let's see what function is evolving when only one selection pressure is applied:

mistake for missed site: a gene that binds pretty much everywhere

mistake for spurious binding within gene: a gene that does not bind within the boundaries of the gene and binds randomly everywhere else

mistake for spurious binding outside gene: a gene that does not bind outside the boundaries of the gene, except possibly at binding sites, and binds randomly within the gene

Now let's recall what is evolving when all three selection pressures are applied:

a gene that binds at all binding sites and nowhere else

Notice how the single-pressure functions are different from the three-pressure function. Now carefully note that Rcapacity does not matter in the single-pressure scenarios. In case you've forgotten:

When binding sites are to be distinguished from all other sites, a reasonably unique pattern must evolve in the binding sites that does not appear anywhere else. This pattern is illustrated by the sequence logo. The number of bits of information required in the pattern is specified by Rfrequency. As the pattern evolves, the number of bits in the sequence logo, Rsequence, approaches Rfrequency. If the bit capacity of the binding sites does not allow Rsequence to approach Rfrequency, then it is much more difficult to evolve a perfect creature.


What your model shows is how difficult it becomes to sort detrimental and beneficial mutations as you lengthen the genome with three selection conditions. Reduce the number of selection conditions to one and your model can easily sort for the beneficial and detrimental mutation.
But this is not interesting if the evolved function is different in the two scenarios. That is why you used to mention that the selection conditions must be applied sequentially and cumulatively, so that the final function is the same as when all three conditions are applied together. We have never done this with Ev.

~~ Paul

[Dr Adequate]

Let’s review what Adequate is alleging.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

You’ve got no code which proves this and you’ve got no real examples of you’re nonexistent code. Mutation and selection simply does not work the way you allege and you’re tantrums will not make what you say to be true.

Adequate, let me show you again how to post a citation of how mutation and selection actually works.

http://links.jstor.org/sici?sici=0027-8424(19961112)93%3A23%3C13152%3ACCTFHI%3E2.0.CO%3B 2-D (http://links.jstor.org/sici?sici=0027-8424(19961112)93%3A23%3C13152%3ACCTFHI%3E2.0.CO%3B 2-D)

See Adequate, you don’t have to throw a tantrum, just post an example of your ridiculous assertion, of course you can’t because mutation and selection doesn’t work that way. Evolution by mutation and selection is slowed (dramatically as the above citation shows) by increasing the number of selection conditions; it is not accelerated as you so irrationally speculate. Adequate, you really are incompetent in the mathematics of mutation and selection. What did you get your PhD in? Was that amathematics? Are you trying to say that you're still too dumb to get it to work?

If not, what is the point of your flatulent ravings?

[krazyKemist]

Anything can be harmful, that is not a good argument "krazyKemist". For example, I can accidently bite by cheek. Therefore teeth are harmful?

It is actually thought to have immune and other functions. See http://www.sciam.com/askexpert_question.cfm?articleID=000CAE56-7201-1C71-9EB7809EC588F2D7 to get educated and to quit yourself from using the sloppy argument in the future.

Uhhh... I use my teeth to chew food. Sometimes, yes I bite my own tongue, but on the whole, I prefer having teeth to not having teeth. Most animals do better with teeth than without. Tonsils and spleen are also useful if not completely essential for life. Same for fingers and limbs.

And you use your appendix for :confused: what exactly ? Back-up tissue is fine, doesn't mean the thing has any function in the adult to begin with. You can also use blood from an umbilical cord for bone marrow transplant, but I don't think you would think it a marvelous idea to trail it around (the cord, I mean) as an adult. Doesn't change my main point : it is bad engineering, if it can cause you to die because of the way it's made. And thanks for the link it's very interesting.

the Kemist

[kleinman]

There is no such thing as your Rcapacity issue. Your model shows that each of the individual selection conditions easily can be satisfied in a tiny number of generations despite longer genome lengths. It is only when you try to run the model and satisfy all three selection conditions simultaneously that the program slows “precipitously”.Let's see what function is evolving when only one selection pressure is applied:

mistake for missed site: a gene that binds pretty much everywhere

mistake for spurious binding within gene: a gene that does not bind within the boundaries of the gene and binds randomly everywhere else

mistake for spurious binding outside gene: a gene that does not bind outside the boundaries of the gene, except possibly at binding sites, and binds randomly within the gene

Now let's recall what is evolving when all three selection pressures are applied:

a gene that binds at all binding sites and nowhere else

Notice how the single-pressure functions are different from the three-pressure function. Now carefully note that Rcapacity does not matter in the single-pressure scenarios. In case you've forgotten:

When binding sites are to be distinguished from all other sites, a reasonably unique pattern must evolve in the binding sites that does not appear anywhere else. This pattern is illustrated by the sequence logo. The number of bits of information required in the pattern is specified by Rfrequency. As the pattern evolves, the number of bits in the sequence logo, Rsequence, approaches Rfrequency. If the bit capacity of the binding sites does not allow Rsequence to approach Rfrequency, then it is much more difficult to evolve a perfect creature.
So you are now proposing that evolution has a goal? You are trying to squirm out of what your own model is showing you. The only reason binding sites be distinguished from all other sites is that you put three selection conditions in your model to determine this. If the binding sites are not distinguished, this affects the fitness of that creature to reproduce because you have defined your model that way. However, you can individually evolve any one of the three selection conditions in your model very rapidly. That is, you can evolve binding sites where they should be, you eliminate spurious binding sites in the non-binding site portion of the genome or you can eliminate spurious binding in the gene very rapidly if done as individual selection pressures. It is only when you try to evolve all three conditions simultaneously that the model becomes profound slow with the longer genome cases. This is exactly analogous to the hundred or so citations of real examples of mutation and selection which show the same mathematical fact. Combination selection pressures profoundly slow down the ability of a population to evolve to these selection pressures.
What your model shows is how difficult it becomes to sort detrimental and beneficial mutations as you lengthen the genome with three selection conditions. Reduce the number of selection conditions to one and your model can easily sort for the beneficial and detrimental mutation.But this is not interesting if the evolved function is different in the two scenarios. That is why you used to mention that the selection conditions must be applied sequentially and cumulatively, so that the final function is the same as when all three conditions are applied together. We have never done this with Ev.
It may not be interesting to you because you are a devout evolutionarian and this shows that your theory of evolution is mathematically impossible. If you were interested in how mutation and selection actually works, you would understand that if multiple selection pressures are applied sequentially they are able to evolve much more rapidly then when applied concurrently. This is explicitly stated in the previous citation I have posted. That is interesting because not only does it prove your theory of evolution to be mathematically impossible, it has important applications to many areas of science and medicine. You evolutionarians would rather advance you mathematically impossible belief system than advance the understanding of how mutation and selection actually works. Now don’t worry Paul, I’ll keep posting examples of how mutation and selection actually works and perhaps some day you will understand what your own mathematical model actually shows. Between these posts, we can watch Adequate throw tantrums.

[Dr Adequate]

So you are now proposing that evolution has a goal? You are trying to squirm out of what your own model is showing you. The only reason binding sites be distinguished from all other sites is that you put three selection conditions in your model to determine this. If the binding sites are not distinguished, this affects the fitness of that creature to reproduce because you have defined your model that way. However, you can individually evolve any one of the three selection conditions in your model very rapidly. That is, you can evolve binding sites where they should be, you eliminate spurious binding sites in the non-binding site portion of the genome or you can eliminate spurious binding in the gene very rapidly if done as individual selection pressures. It is only when you try to evolve all three conditions simultaneously that the model becomes profound slow with the longer genome cases. This is exactly analogous to the hundred or so citations of real examples of mutation and selection which show the same mathematical fact. Combination selection pressures profoundly slow down the ability of a population to evolve to these selection pressures.

It may not be interesting to you because you are a devout evolutionarian and this shows that your theory of evolution is mathematically impossible. If you were interested in how mutation and selection actually works, you would understand that if multiple selection pressures are applied sequentially they are able to evolve much more rapidly then when applied concurrently. This is explicitly stated in the previous citation I have posted. That is interesting because not only does it prove your theory of evolution to be mathematically impossible, it has important applications to many areas of science and medicine. You evolutionarians would rather advance you mathematically impossible belief system than advance the understanding of how mutation and selection actually works. Now don’t worry Paul, I’ll keep posting examples of how mutation and selection actually works and perhaps some day you will understand what your own mathematical model actually shows. Between these posts, we can watch Adequate throw tantrums. There don't appear to be any new lies in this drivel.

[kleinman]

There don't appear to be any new lies in this drivel.
Again for all of you who haven’t read this entire thread, here is what Adequate is asserting.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
So we continue to wait for Adequate to cite an example where multiple selection pressures accelerate evolution. Again Adequate let me show you how you post a citation to support your hypothesis; of course this citation supports my hypothesis and the mathematics which ev demonstrates that multiple selection pressures slow the evolutionary process.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10669360&dopt=AbstractPlus (http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10669360&dopt=AbstractPlus)
Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.
Simple isn’t it Adequate? Of course, you first need a reasonable mathematical model to explain the empirical findings and you don’t have a reasonable mathematical model. If fact, you don’t even have a model, you only have a silly gif (and a lot of whining that you think explains your silly gif).

[Dr Adequate]

Again for all of you who haven’t read this entire thread, here is what Adequate is asserting.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

So we continue to wait for Adequate to cite an example where multiple selection pressures accelerate evolution. Again Adequate let me show you how you post a citation to support your hypothesis; of course this citation supports my hypothesis and the mathematics which ev demonstrates that multiple selection pressures slow the evolutionary process.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10669360&dopt=AbstractPlus (http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10669360&dopt=AbstractPlus)

Simple isn’t it Adequate? Of course, you first need a reasonable mathematical model to explain the empirical findings and you don’t have a reasonable mathematical model. If fact, you don’t even have a model, you only have a silly gif (and a lot of whining that you think explains your silly gif). To summarise:

You have no critque of my model.

You have no counterexample to my model.

You have no evidence supporting your delusions.

You have no computer model supporting your delusions.

You haven't thought of any new lies.

[kleinman]

To summarise:

You have no critque of my model.

You have no counterexample to my model.

You have no evidence supporting your delusions.

You have no computer model supporting your delusions.

You haven't thought of any new lies.
You have no model.

I have given over 100 counterexamples and I have another for you at the end of this post. We are still waiting for you to post your first example of your model.

I have only the evidence of a peer reviewed and published mathematical model of mutation and selection and over 100 citations showing empirical evidence of the results of this model.

So what is your assertion? Let’s post it again.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
You say that multiple selection pressures accelerate evolution and I say multiple selection pressures profoundly slow evolution. You have a silly gif and no examples of your silly gif, I have the results from the ev computer simulation which is peer reviewed and published. In addition, I have posted over 100 real examples of this mathematical result. Here Adequate, have another citation. This one is for the crowd over at the National Cancer Institute as well since the writer of the simulation, Dr Tom Schneider, which shows the results I am using to prove my case, works there.

http://cancerres.aacrjournals.org/cgi/content/full/59/11/2511 (http://cancerres.aacrjournals.org/cgi/content/full/59/11/2511)

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment.
and
These results have several significant implications for the hormonal therapy of PCa: (a) the selection for rare tumor cells with mutant ARs indicates that AR antagonists may improve responses to androgen ablation therapy initially but subsequently accelerate the growth of surviving tumor cells; (b) alternative methods to further block the AR-mediated signaling that appears critical for tumor cell survival, such as targeting AR-associated coactivator proteins, downstream target genes, or signal transduction pathways that interact with the AR, may enhance responses to androgen ablation monotherapy or combined androgen blockade; and (c) the additive or synergistic effects of cytotoxic chemotherapy used early in conjunction with androgen ablation therapy may be very effective if, as this study suggests, only a relatively small number of tumor cells survive combined androgen blockade.
So Adequate, when are you going to post your first real example of your silly gif?

[quixotecoyote]

Not that I object, but why do you keep posting the parts where Dr. A provides evidence and you do not?

eta:My mistake, you actually posted those last two excerpts yourself, which when parsed ay the following:

Applying multiple selection pressures (androgen blockade & flutamide) to the cancer is speeding the evolution of the cancer. This requires further countermeasures.

If this is not what your excerpt is saying, you need to explain it better

[joobz]

function t(selected: integer; genes: integer): integer;
var genome: array[0 .. 1, 1 .. pop, 1 .. 10] of boolean;
fitness: array[0 .. 1, 1 .. pop] of real;
c, g, h, g1, g2, i, j, o, n, fixed, generations: integer;
flag: boolean;

begin

o:=0; n:=1;
for i:=1 to pop do for j:=1 to genes do genome[0,i,j]:=false;
for i:=1 to pop do fitness[0,i]:=1;

generations:=0;

repeat
c:=0;

repeat
c:=c+1;
g1:=1+random(pop);
g2:=1+random(pop);
if fitness[o,g1]*random > fitness[o,g2]*random then g:=g1 else g:=g2;
for j:=1 to genes do genome[n,c,j]:=genome[o,g,j];
fitness[n,c]:=fitness[o,g];
if random(50)=0 then
begin
j:=1+random(10);
genome[n,c,j]:=not(genome[n,c,j]);
if (genome[n,c,j]) and (j<=selected) then fitness[n,c]:=fitness[n,c]*1.25 else fitness[n,c]:=fitness[n,c]/1.25;
end;
until c=pop;

fixed:=0;
for j:=1 to selected do
begin
flag:=true;
for i:=1 to pop do flag:=flag and genome[n,i,j];
if flag then fixed:=fixed+1;
end;
if fixed=selected then
begin
selected:=selected+1;
if selected<=genes then
for i:=1 to pop do if genome[n,i,selected] then fitness[n,i]:=fitness[n,i]*1.25;
end;

o:=1-o; n:=1-n;
generations:=generations+1;

until (fixed=genes);

t:=generations;

end;

Adequate thinks he can fool people with this nonsense so let’s see what happens when we run this code fragment through a Pascal compiler.

pas:3: undeclared identifier `pop' (first use in this routine)



Hello, moron?

You remember I said that population was constant?

So, hey, why don't you declare pop as a constant?


:D :D
That's the funniest thing I've seen Kleinman do in a long time.
Thanks for the laugh.

[Dr Adequate]

You have no model. I guess this is a new lie.

Everyone can see that you're lying, kleinman.


I have given over 100 counterexamples and I have another for you at the end of this post. We are still waiting for you to post your first example of your model.

I have only the evidence of a peer reviewed and published mathematical model of mutation and selection and over 100 citations showing empirical evidence of the results of this model.

So what is your assertion? Let’s post it again.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

You say that multiple selection pressures accelerate evolution and I say multiple selection pressures profoundly slow evolution. You have a silly gif and no examples of your silly gif, I have the results from the ev computer simulation which is peer reviewed and published. In addition, I have posted over 100 real examples of this mathematical result. Here Adequate, have another citation. This one is for the crowd over at the National Cancer Institute as well since the writer of the simulation, Dr Tom Schneider, which shows the results I am using to prove my case, works there.

http://cancerres.aacrjournals.org/cgi/content/full/59/11/2511 (http://cancerres.aacrjournals.org/cgi/content/full/59/11/2511)

and

So Adequate, when are you going to post your first real example of your silly gif? So, to summarise:

You have no critque of my model.

You have no counterexample to my model.

You have no evidence supporting your delusions.

You have no computer model supporting your delusions.

Youhave thought of another crazy lie, which everyone reading this thread can see is a lie.

Why do you tell lies when you know you're going to get caught?

[quixotecoyote]

I was going to append my earlier post again, but the thread is moving too fast.

I came across the term 'extinction pressure' in literature related to the evolution of bedbugs. Could that be what Kleinman is acutally referring to?

[kleinman]

You have no model.I guess this is a new lie.

Everyone can see that you're lying, kleinman.
Really? Which is it, your silly graph with no real examples of this type of mathematical behavior or is it your code fragment with compile time errors?

Here’s another example which shows that multiple selection pressures slow evolution.
http://en.wikipedia.org/wiki/Antiretroviral_drug (http://en.wikipedia.org/wiki/Antiretroviral_drug)
The life cycle of HIV can be as short as about 1.5 days: from viral entry into a cell; through replication, assembly, and release of additional viruses; to infection of other cells. HIV lacks proofreading enzymes to correct errors made when it converts its RNA into DNA via reverse transcription. Its short life cycle and high error rate cause the virus to mutate very rapidly, resulting in a high genetic variability of HIV. Most of the mutations either are inferior to the parent virus (often lacking the ability to reproduce at all) or convey no advantage, but some of them have a natural selection superiority to their parent and can enable them to slip past defenses such as the human immune system and antiretroviral drugs. The more active copies of the virus, the greater the possibility that one resistant to antiretroviral drugs will be made, so antiretroviral combination therapy defends against resistance by suppressing HIV replication as much as possible.

Combinations of antiretrovirals create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility of a superior mutation. If a mutation arises that conveys resistance to one of the drugs being taken, the other drugs continue to suppress reproduction of that mutation. With rare exceptions, no individual antiretroviral drug has been demonstrated to suppress an HIV infection for long; these agents must be taken in combinations in order to have a lasting effect. As a result the standard of care is to use combinations of antiretroviral drugs. Combinations usually comprise two nucleoside-analogue RTIs and one non-nucleoside-analogue RTI or protease inhibitor.[2]
So Adequate, when are you going to post an example which shows that multiple selection pressures accelerate evolution? Why not post your full code which mathematically shows that multiple selection pressures accelerate evolution? You have got no examples of your ridiculous assertion and you have no model which shows that multiple selection pressures accelerate evolution. All you have is whining and tantrums. The theory of evolution by mutation and selection is mathematically impossible. If you understood how mutation and selection works mathematically, you would agree with this, but you don’t Dr Adequate, PhD in amathematics.

[Dr Adequate]

Really? Which is it, your silly graph with no real examples of this type of mathematical behavior or is it your code fragment with compile time errors?

Here’s another example which shows that multiple selection pressures slow evolution.
http://en.wikipedia.org/wiki/Antiretroviral_drug (http://en.wikipedia.org/wiki/Antiretroviral_drug)

So Adequate, when are you going to post an example which shows that multiple selection pressures accelerate evolution? Why not post your full code which mathematically shows that multiple selection pressures accelerate evolution? You have got no examples of your ridiculous assertion and you have no model which shows that multiple selection pressures accelerate evolution. All you have is whining and tantrums. The theory of evolution by mutation and selection is mathematically impossible. If you understood how mutation and selection works mathematically, you would agree with this, but you don’t Dr Adequate, PhD in amathematics. To summarise:

You have no critique of my model.

You have no counterexample to my model.

You are still so frightened of my model that you babble out the hysterical lie that I "have no model".

You have no evidence supporting your delusions.

You have no computer model supporting your delusions.

You haven't thought of any new lies.

[Mr. Scott]

Dr. Kleinman, is Dennis Powell an evolutionist?

[Belz...]

So... has Klein actually shown his mathematical proof, or does he just keep claiming that he simply has it ?

[kleinman]

So, you mathematically challenged evolutionarians still haven’t figured out how mutation and selection actually works. So again, here’s how mutation and selection works. Mutation and selection is a sorting problem of beneficial and detrimental mutations. The mathematics of mutation and selection is very similar to systems optimization, database sorting and a variety of iterative problem solving solutions seen all throughout science and mathematics. The basic principle of these types of problems is that the fewer the number of sorting conditions, the easier and more rapidly you can solve these problems. Dr Schneider’s ev program elegantly demonstrates this effect with the profoundly slow convergence of his model when all three selection (sorting) conditions are applied and the extremely rapid convergence of his model when only a single selection (sorting) condition is applied. This same mathematical effect is seen in the empirical data as shown in the citations I have and will continue to post, that is multiple simultaneous selection (sorting) conditions profoundly slows the evolutionary process. So let’s see what you dim bulbs of evolutionism have to say today about the mathematics of mutation and selection.
To summarise:
Yes Adequate, let’s summarize what you have to say.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Let’s not forget your code fragment that you have posted that doesn’t compile. I think we can say that your view of the mathematics of mutation and selection does not compute.
http://www.randi.org/forumlive/images/icons/icon5.gif Annoying
You are not at all annoying pussycat but I can see why you would want to change the subject. After all, your silly theory of evolution has been proved mathematically impossible and the empirical data confirms this. Mutation and selection simply does not work the way you evolutionarians allege. So how does mutation and selection work? Here’s another example which shows how mutation and selection works.

http://aac.asm.org/cgi/content/full/49/5/1671 (http://aac.asm.org/cgi/content/full/49/5/1671)
The inclusion of ZDV with ABC, 3TC, and TDF as quadruple therapy appears to result in a greater degree of viral suppression than that seen with the suboptimal triple combination of ABC, 3TC, and TDF, although these regimens have not been directly compared. It is conceivable that the inclusion of ZDV with ABC, 3TC, and TDF provided sufficient antiviral coverage to prevent selection of the K65R substitution. A possible reason for the early virologic nonresponsiveness with certain of these triple-NRTI regimens is a low genetic barrier to resistance on the part of the combination that allows the rapid emergence of M184V with or without K65R. The combination of TDF and ddI or TDF and ABC, either in a triple-NRTI regimen or as the dual-NRTI backbone in combination with a PI or NNRTI, are currently not recommended. In contrast, the 3TC and ABC combination and the 3TC and TDF combination seem to be effective NRTI backbones when they are used together with an NNRTI or a PI. Triple-NRTI regimens containing ZDV continue to play an important role in ART as an alternative to PI- and NNRTI-containing regimens as initial therapy, as simplified therapy, and in some quadruple regimens (5, 21, 25, 29; J. A. Bartlett, J. Johnson, G. Herrera, N. Sosa, A. E. Rodriguez, and M. S. Shaefer, Abstr. XIV Int. AIDS Conf., abstr. TuOrB1189, 2002; M. Markowitz, J. M. Lang, E. DeJesus, C. Hill-Zabala, E. R. Lanier, Q. Liao, K. Pappa, and M. Shaefer, Abstr. Int. AIDS Soc. 2nd Conf. Pathogen. Treatment, abstr. 42, 2003). Evidence also suggests that a triple-NRTI regimen that includes ZDV remains a rational treatment approach for many patients, especially those who initiate therapy with low viral loads (Ait Khaled et al., Abstr. XI Int. HIV Drug Res. Workshop; Melby et al., Abstr. 8th Conf. Retrov. Opportunistic Infect.). Several studies have suggested that the triple combination of ZDV, ABC, and 3TC is less potent than two NRTIs plus either a PI or an NNRTI (12, 25, 29). Although the difference in potency between PIs and triple NRTIs may often be overcome by an adherence advantage among patients with lower baseline viral loads, this may not be the case when regimens consisting of triple NRTIs are compared with those containing EFV and two NRTIs (12, 25, 29).
Why Adequate, perhaps you want to explain why four drug therapy works better than three drug therapy for the treatment of HIV? Didn’t you say that the greater the number of selection pressures the more rapidly evolution proceeds? There seems to be a contradiction between your assertion and reality.

I think you evolutionarians need to go back to the drawing board. The theory of evolution by mutation and selection is mathematically impossible.

[Mr. Scott]

I can see why you would want to change the subject.

The subject is creationists, evolutionists, and being annoying. I don't see why you chose to refuse to answer my question.

Is Dennis Powell an evolutionist?

[krazyKemist]

Not that I object, but why do you keep posting the parts where Dr. A provides evidence and you do not?

eta:My mistake, you actually posted those last two excerpts yourself, which when parsed ay the following:

Applying multiple selection pressures (androgen blockade & flutamide) to the cancer is speeding the evolution of the cancer. This requires further countermeasures.

If this is not what your excerpt is saying, you need to explain it better

Just a little precision: flutamide is an antiandrogen, and is supposed to be blocking androgen-stimulated mitosis. Androgen blocade is usually effected with two drugs : an antiandrogen (at AR level) and a LHRH superagonist (to stop secretion of testo from the testis, so there's less androgen competing with the antiandrogen for receptor binding).

But what Kleinman doesn't know is that the androgen receptor is actually already mutated (under no drug influence) in most if not all prostate cancer cases (no prostate cancer cell lines exist with a native receptor. None.). It tends to be activated permanently without the need for androgens, making an antiandrogen less efficient. This effect becomes more pronounced with time as the cells adapt to the absence of androgens (no new mutations are needed for this; the expression level of a kinase can simply be elevated to do the trick). The effect is also known for ER+ breast cancer (even if the ER is that case is not mutated). The paper actually proposes blocade at coactivator level as a way to circumvent this.

the Kemist

[kjkent1]

So, you mathematically challenged evolutionarians still haven’t figured out how mutation and selection actually works. So again, here’s how mutation and selection works. Mutation and selection is a sorting problem of beneficial and detrimental mutations. The mathematics of mutation and selection is very similar to systems optimization, database sorting and a variety of iterative problem solving solutions seen all throughout science and mathematics. The basic principle of these types of problems is that the fewer the number of sorting conditions, the easier and more rapidly you can solve these problems. Dr Schneider’s ev program elegantly demonstrates this effect with the profoundly slow convergence of his model when all three selection (sorting) conditions are applied and the extremely rapid convergence of his model when only a single selection (sorting) condition is applied. This same mathematical effect is seen in the empirical data as shown in the citations I have and will continue to post, that is multiple simultaneous selection (sorting) conditions profoundly slows the evolutionary process.Despite your continued protestations, you cannot explain away the fact that there exists a myriad of biological organisms, and both a fossil and genetic audit trail backwards through the ages.

For each of your articles on various drug therapies, none concludes absolute success. In fact, the opposite is true -- resistance eventually appears in some subset of the test population during each experiment.

And, that is all that is required to falsify your claims.

Schneider's ev model "is" elegant. It shows information gain from a random start using an extremely simple set of selection conditions and random point mutation. But, it is not a complete model of the evolutionary landscape, because it does not utilize anything more than point mutation, nor does it select for anything other than missed and/or spurious bindings.

In sum, what you have shown throughout this thread is that:

(1) information gain in an mathematically modeled genome occurs;
(2) evolution occurs despite the imposition of a host of narrowly targeted experiments specifically intended to stop the evolutionary process;
(3) you have no alternative scientific theory to evolution;
(4) you believe in magic (the instantaneous creation of all life forms by means of an unknowable power which is beyond the realm of scientific understanding).

The sad thing about all this is that you're obviously a very bright person. But, you allow your religious fervor to overwhelm your analytical powers, with the result that no one will seriously entertain your arguments.

At best, you may reasonably argue that the history of organic life on Earth requires more than point mutation and selection for missed and spurious bindings. But, the evidence demonstrates conclusively that the additional processes necessary to achieving the evolution of life exist -- they have been observed and verified. So, it's unreasonable to infer that because a small subset of evolutionary processes is insufficient to explain the existence of life, that evolution by any means is therefore impossible.

The true inference is that life is here, and evidence of its evolution is everywhere. And, while the Christian Bible is certainly a great read, it's no more scientific than the "Lord of the Rings."

[Dr Adequate]

So, you mathematically challenged evolutionarians still haven’t figured out how mutation and selection actually works. So again, here’s how mutation and selection works. Mutation and selection is a sorting problem of beneficial and detrimental mutations. The mathematics of mutation and selection is very similar to systems optimization, database sorting and a variety of iterative problem solving solutions seen all throughout science and mathematics. The basic principle of these types of problems is that the fewer the number of sorting conditions, the easier and more rapidly you can solve these problems. Dr Schneider’s ev program elegantly demonstrates this effect with the profoundly slow convergence of his model when all three selection (sorting) conditions are applied and the extremely rapid convergence of his model when only a single selection (sorting) condition is applied. This same mathematical effect is seen in the empirical data as shown in the citations I have and will continue to post, that is multiple simultaneous selection (sorting) conditions profoundly slows the evolutionary process. So let’s see what you dim bulbs of evolutionism have to say today about the mathematics of mutation and selection.

Yes Adequate, let’s summarize what you have to say.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

Let’s not forget your code fragment that you have posted that doesn’t compile. I think we can say that your view of the mathematics of mutation and selection does not compute.

You are not at all annoying pussycat but I can see why you would want to change the subject. After all, your silly theory of evolution has been proved mathematically impossible and the empirical data confirms this. Mutation and selection simply does not work the way you evolutionarians allege. So how does mutation and selection work? Here’s another example which shows how mutation and selection works.

http://aac.asm.org/cgi/content/full/49/5/1671 (http://aac.asm.org/cgi/content/full/49/5/1671)
So, you've got nothing?

Why Adequate, perhaps you want to explain why four drug therapy works better than three drug therapy for the treatment of HIV? We've done so, remember? You were too stupid to understand the explanation, remember? So you started screaming hysterical nonsense about cheese, remember?

Didn’t you say that the greater the number of selection pressures the more rapidly evolution proceeds? There seems to be a contradiction between your assertion and reality. No.


I think you evolutionarians need to go back to the drawing board. The theory of evolution by mutation and selection is mathematically impossible. Remember, reciting this stupid trash over and over won't make it true. You remember I explained that to you? About your lies not giving you magic powers to change reality? Remember that?

[Dr Adequate]

So... has Klein actually shown his mathematical proof, or does he just keep claiming that he simply has it ? You're actually asking whether kleinman is lying?

Of course he's lying.

For one thing, his math skills would disgrace a teenager. If there was a mathematical disproof of evolution, he'd be the last person in the world to understand it.

And for another thing, he's kleinman.

[Paul C. Anagnostopoulos]

So you are now proposing that evolution has a goal? You are trying to squirm out of what your own model is showing you. The only reason binding sites be distinguished from all other sites is that you put three selection conditions in your model to determine this. If the binding sites are not distinguished, this affects the fitness of that creature to reproduce because you have defined your model that way. However, you can individually evolve any one of the three selection conditions in your model very rapidly. That is, you can evolve binding sites where they should be, you eliminate spurious binding sites in the non-binding site portion of the genome or you can eliminate spurious binding in the gene very rapidly if done as individual selection pressures. It is only when you try to evolve all three conditions simultaneously that the model becomes profound slow with the longer genome cases. This is exactly analogous to the hundred or so citations of real examples of mutation and selection which show the same mathematical fact. Combination selection pressures profoundly slow down the ability of a population to evolve to these selection pressures.
What you are saying here is that I can easily make a wheel spin, easily make a seat, and easily make gasoline explode, but when I try to build a car it gets more "complicated." Big woop.

Note that if there is only one pressure, then there are no spurious bindings, because the word spurious only makes sense when the three-pressure function is evolving. You'll see that I did not use the word spurious in my post, except to refer to the controls in the dialog.

Note also that you completely ignored the subject of my post: Rcapacity.


... If you were interested in how mutation and selection actually works, you would understand that if multiple selection pressures are applied sequentially they are able to evolve much more rapidly then when applied concurrently. ...
You mean when multiple selection pressures are applied sequentially and cumulatively. Otherwise the same function is not evolving. Unfortunately, we have never performed such experiments with Ev. So what the hell are you talking about?

~~ Paul

[Dr Adequate]

You mean when multiple selection pressures are applied sequentially and cumulatively. Otherwise the same function is not evolving. Unfortunately, we have never performed such experiments with Ev. So what the hell are you talking about? Well, he would appear to be telling lies.

I'm shocked, I tell you, shocked!

[Dr Adequate]

Let's see if we can explain it in language that kleinman would understand. Suppose a stupid lunatic thinks he hears a magic sky fairy telling him to gather two of every kind of animal.

Because he's a halfwit, he goes wandering around at random looking for the animals.

Now, consider the following two options:

(1) He collects the animals he stumbles across in strict alphabetical order, starting with aardvarks and working his way along the list. If he happens to see an animal, and it's not the next one on his list, he ignores it.

(2) When he sees an animal, if he hasn't already got a pair, he collects it.

Which method do you think would be faster?

NOTE FOR COMPLETE MORONS, I.E. KLEINMAN: the fact that both methods take longer the more animals there are on the list does not somehow magically mean that the first method is better.

[kleinman]

Are you evolutionarians still having trouble understanding the mathematics of mutation and selection? Don’t worry; we’ll help you understand how it works.
So you are now proposing that evolution has a goal? You are trying to squirm out of what your own model is showing you. The only reason binding sites be distinguished from all other sites is that you put three selection conditions in your model to determine this. If the binding sites are not distinguished, this affects the fitness of that creature to reproduce because you have defined your model that way. However, you can individually evolve any one of the three selection conditions in your model very rapidly. That is, you can evolve binding sites where they should be, you eliminate spurious binding sites in the non-binding site portion of the genome or you can eliminate spurious binding in the gene very rapidly if done as individual selection pressures. It is only when you try to evolve all three conditions simultaneously that the model becomes profound slow with the longer genome cases. This is exactly analogous to the hundred or so citations of real examples of mutation and selection which show the same mathematical fact. Combination selection pressures profoundly slow down the ability of a population to evolve to these selection pressures.What you are saying here is that I can easily make a wheel spin, easily make a seat, and easily make gasoline explode, but when I try to build a car it gets more "complicated." Big woop.
Why sure it is a big woop Paul, that’s why your theory of evolution is mathematically impossible. Your own model shows that three selection pressures profoundly slow the rate of evolution on longer genomes. Apply only a single selection pressure in your model and the rate of convergence for this single selection pressure is 10’s of thousands of times faster than when the model is converging this selection condition in combination with the other two selection conditions. This same affect is seen in the empirical evidence. See the citation which I have posted below.
Note that if there is only one pressure, then there are no spurious bindings, because the word spurious only makes sense when the three-pressure function is evolving. You'll see that I did not use the word spurious in my post, except to refer to the controls in the dialog.
So what? Each of the individual selection conditions, evolving the binding sites, eliminating the spurious binding in the genes and eliminating the spurious binding outside the binding site region easily evolve on the longer genomes when done individually. It is only when the model tries to evolve all three conditions simultaneously that the evolutionary process is profoundly slowed. This is the main lesson that your model has to teach about the mathematics of mutation and selection because this is what is observed empirically in real mutation selection situations. Single selection conditions are far more easily evolved by mutation and selection than multiple concurrent selection conditions. That is how mutation and selection works in reality.
Note also that you completely ignored the subject of my post: Rcapacity.
I haven’t ignored your concept of Rcapacity; I have shown you that it is not real. The reason ev does not converge with longer genomes is the three simultaneous selections. Each of the three selection conditions are easily satisfied individually, it is only when you try to converge the selection conditions simultaneously that the model becomes profoundly slow. And you know what? That is how mutation and selection behaves in reality. Single selection pressures can be adapted to very easily by viruses and bacteria, it is when you apply multiple selection pressures simultaneously that the mutation selection process for evolution becomes profoundly slow. Read the citation below, it clearly demonstrates this fact.
... If you were interested in how mutation and selection actually works, you would understand that if multiple selection pressures are applied sequentially they are able to evolve much more rapidly then when applied concurrently. ...You mean when multiple selection pressures are applied sequentially and cumulatively. Otherwise the same function is not evolving. Unfortunately, we have never performed such experiments with Ev. So what the hell are you talking about?
I think you are confused Paul. Evolution is not about function, it is about fitness of a population to reproduce.
Let's see if we can explain it in language that kleinman would understand.
Oh Adequate, I understand your language perfectly, here let’s post again what you have said about how mutation and selection works.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
And let’s not forget your code fragment that doesn’t compile. So you have a silly graph which you say shows that multiple selection pressures accelerate evolution but you don’t have a real example of this. I contend that multiple selection pressures slow evolution and you say multiple selection pressures accelerate evolution. I have a peer reviewed and published model of random point mutations which shows this and you have, well a silly graph and a noncompiling code fragment. Let me show you again how to post a citation which supports your contention (well, supports my contention because you don’t have any examples to support your contention).

http://jac.oxfordjournals.org/cgi/content/full/56/2/353 (http://jac.oxfordjournals.org/cgi/content/full/56/2/353)
Objectives: The aim of this study was to evaluate the ability of levofloxacin and ciprofloxacin alone and in combination with either ceftazidime, cefepime, imipenem, piperacillin–tazobactam or amikacin to select for antibiotic-resistant mutants of Pseudomonas aeruginosa and Acinetobacter spp.

Methods: Clinical strains of P. aeruginosa (n = 5) and Acinetobacter spp. (n = 5) susceptible to all the drugs used in the study were assayed. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MICs were determined after five serial passages on antibiotic-gradient plates containing each antibiotic alone or in combination with levofloxacin or ciprofloxacin. Acquisition of resistance was defined as an increase of 4-fold from the starting MIC. In single-step studies, the frequency of spontaneous mutations was calculated after a passage on plates containing antibiotics alone and in combinations at concentrations equal to the highest NCCLS breakpoints.

Results: Serial passages on medium containing single antibiotics resulted in increased MICs for each antibiotic; MIC increases were limited by antibiotics in combination. A decrease in the number of strains with MICs above the NCCLS breakpoints occurred when fluoroquinolones were combined with a second antibiotic for both P. aeruginosa and Acinetobacter spp. isolates. Frequencies of mutation were higher for antibiotics alone than for combinations.

Conclusions: Use of combinations of fluoroquinolones with ß-lactams and amikacin reduces the risk for in vitro selection of resistant P. aeruginosa and Acinetobacter spp.
See Adequate, isn’t that simple and in a language everyone can understand. It is another example which shows why the theory of evolution is mathematically impossible.

[Dr Adequate]

Are you evolutionarians still having trouble understanding the mathematics of mutation and selection? Don’t worry; we’ll help you understand how it works.

Why sure it is a big woop Paul, that’s why your theory of evolution is mathematically impossible. Your own model shows that three selection pressures profoundly slow the rate of evolution on longer genomes. Apply only a single selection pressure in your model and the rate of convergence for this single selection pressure is 10’s of thousands of times faster than when the model is converging this selection condition in combination with the other two selection conditions. This same affect is seen in the empirical evidence. See the citation which I have posted below.

So what? Each of the individual selection conditions, evolving the binding sites, eliminating the spurious binding in the genes and eliminating the spurious binding outside the binding site region easily evolve on the longer genomes when done individually. It is only when the model tries to evolve all three conditions simultaneously that the evolutionary process is profoundly slowed. This is the main lesson that your model has to teach about the mathematics of mutation and selection because this is what is observed empirically in real mutation selection situations. Single selection conditions are far more easily evolved by mutation and selection than multiple concurrent selection conditions. That is how mutation and selection works in reality.

I haven’t ignored your concept of Rcapacity; I have shown you that it is not real. The reason ev does not converge with longer genomes is the three simultaneous selections. Each of the three selection conditions are easily satisfied individually, it is only when you try to converge the selection conditions simultaneously that the model becomes profoundly slow. And you know what? That is how mutation and selection behaves in reality. Single selection pressures can be adapted to very easily by viruses and bacteria, it is when you apply multiple selection pressures simultaneously that the mutation selection process for evolution becomes profoundly slow. Read the citation below, it clearly demonstrates this fact.

I think you are confused Paul. Evolution is not about function, it is about fitness of a population to reproduce.

Oh Adequate, I understand your language perfectly, here let’s post again what you have said about how mutation and selection works.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

And let’s not forget your code fragment that doesn’t compile. So you have a silly graph which you say shows that multiple selection pressures accelerate evolution but you don’t have a real example of this. I contend that multiple selection pressures slow evolution and you say multiple selection pressures accelerate evolution. I have a peer reviewed and published model of random point mutations which shows this and you have, well a silly graph and a noncompiling code fragment. Let me show you again how to post a citation which supports your contention (well, supports my contention because you don’t have any examples to support your contention).

http://jac.oxfordjournals.org/cgi/content/full/56/2/353 (http://jac.oxfordjournals.org/cgi/content/full/56/2/353)

See Adequate, isn’t that simple and in a language everyone can understand. It is another example which shows why the theory of evolution is mathematically impossible. So, you've still got nothing? Just the same old lies over and over?

Poor kleinman.

BTW, am I to take it from your pitiful bleating about a "non-compiling code fragment" that you don't know how to declare a constant or call a function?

Well, feel free to come crawling to me for help.

[joobz]

And let’s not forget your code fragment that doesn’t compile.
Don't worry, Kleinman. We won't. Why would we forget an example of your complete ineptitude?
http://forums.randi.org/showpost.php?p=2816395&postcount=5066

[kleinman]

So, you've still got nothing?
It’s a bit sad to see how slow you mathematically challenged evolutionarians are in understanding the mathematics of mutation and selection. I think a prolonged session of citations posting is just the thing to clear your brainwashed and biased thought processes.

http://links.jstor.org/sici?sici=0027-8424(19930615)90%3A12%3C5653%3ARIVSOH%3E2.0.CO%3B2-N#abstract (http://links.jstor.org/sici?sici=0027-8424(19930615)90%3A12%3C5653%3ARIVSOH%3E2.0.CO%3B2-N#abstract)
Resistant variants of human immunodeficiency virus type 1 (HIV-1) have been selected by limited passage in MT4 cells of both wild-type and 3'-azido-3'-deoxythymidine (AZT, zidovudine)-resistant strains with the nucleoside analogues (-)-2'-deoxy-3'-thiacytidine (3TC) and (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC). Virus variants selected independently were crossresistant to both inhibitors. This rapid in vitro selection of resistant virus has not previously been seen with nucleoside analogues but is reminiscent of that observed with the nonnucleoside reverse transcriptase inhibitors. However, passage of wild-type virus with a combination of AZT and FTC appreciably delayed emergence of FTC-resistant virus. DNA sequence analysis of the reverse transcriptase coding region from FTC-resistant virus revealed changes at codon 184 in the highly conserved Tyr, Met, Asp, Asp (YMDD) region. When the mutation Met$^{184}->Val was introduced into the infectious clone HXB2, this change alone accounted for the resistance (>1000-fold) seen with both 3TC and FTC, and for a 5- to 15-fold reduction in sensitivity to their (+) enantiomers. It had no effect on susceptibility to AZT or nevirapine and minimal effect on susceptibility to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. To determine the influence of this mutation in a background of mutations conferring resistance to AZT and nonnucleoside reverse transcriptase inhibitors, a series of HIV-1 variants were created by site-directed mutagenesis. All mutants with Met$^{184}->Val were crossresistant to 3TC and FTC. The Met$^{184}->Val mutation did not influence nevirapine resistance, but resistance to AZT was suppressed. Similar suppression of AZT resistance was seen with Tyr$^{181}->Cys. Interestingly, when both Met$^{184}->Val and Tyr$^{181}->Cys substitutions were present, highly resistant virus reverted to complete AZT sensitivity. Assessment of the interactive effects of multiple drug-resistance mutations may help to establish a rationale for using these drugs in the future therapy of HIV disease.
See Adequate, doesn’t that feel better?

[Dr Adequate]

It’s a bit sad to see how slow you mathematically challenged evolutionarians are in understanding the mathematics of mutation and selection. I think a prolonged session of citations posting is just the thing to clear your brainwashed and biased thought processes.

http://links.jstor.org/sici?sici=0027-8424(19930615)90%3A12%3C5653%3ARIVSOH%3E2.0.CO%3B2-N#abstract (http://links.jstor.org/sici?sici=0027-8424(19930615)90%3A12%3C5653%3ARIVSOH%3E2.0.CO%3B2-N#abstract)

See Adequate, doesn’t that feel better? So, you have no evidence for your halfwitted fantasies?

That figures.

[kleinman]

And let’s not forget your code fragment that doesn’t compile.Don't worry, Kleinman. We won't. Why would we forget an example of your complete ineptitude?
Wow joobz, did you get the compiler errors out of Adequate’s nonsense code? Now if you only could remove Adequate’s logic errors, of course, as an alchemical engineer, logic errors are a way of life to you. Joobz, perhaps you could post a real example of Adequate’s irrational logic?

If any of you were wondering what happened to the alchemists from the dark ages, here’s your answer, they became evolutionarians. Here’s an example of how an alchemist, whoops, an evolutionarian thinks.
Envision a system of millions of forming and destructive chemical reactions. Now, envision that intermediates of there reactions associate through non-covalent means and that this complex becomes protected against the destructive reactive pathway, perhaps by a reversible precipitation. These new complexes result in a localized increased of new chemical species. These chemical species then progress in a new series of reaction... that is what I mean through cooperative means. I acknowledge this is complete speculation, but well within the range of chemical possibility. As long as there was enough free energy for these reaction to occur.
You see, if the sun beats down long enough on lead, it turns into gold.

Hey joobz, I see you got yourself a new avatar, were you tired of being the clown fish, can’t brain?

[Dr Adequate]

Wow joobz, did you get the compiler errors out of Adequate’s nonsense code? Now if you only could remove Adequate’s logic errors, of course, as an alchemical engineer, logic errors are a way of life to you. Joobz, perhaps you could post a real example of Adequate’s irrational logic?

If any of you were wondering what happened to the alchemists from the dark ages, here’s your answer, they became evolutionarians. Here’s an example of how an alchemist, whoops, an evolutionarian thinks.
[/COLOR][/COLOR]
You see, if the sun beats down long enough on lead, it turns into gold.[/FONT]

Hey joobz, I see you got yourself a new avatar, were you tired of being the clown fish, can’t brain? Am I to gather from your snivelling about compiler errors that you're still too dumb to write a constant declaration?

This is fun, isn't it? Either you have to admit that the function works, or you have to admit that you're too dumb to follow simple instructions, or you can run away from the question like the whining little coward you are.

[joobz]

Wow joobz, did you get the compiler errors out of Adequate’s nonsense code? Now if you only could remove Adequate’s logic errors, of course, as an alchemical engineer, logic errors are a way of life to you. Joobz, perhaps you could post a real example of Adequate’s irrational logic?

If any of you were wondering what happened to the alchemists from the dark ages, here’s your answer, they became evolutionarians. Here’s an example of how an alchemist, whoops, an evolutionarian thinks.
[/color][/color]
You see, if the sun beats down long enough on lead, it turns into gold.[/font]

Hey joobz, I see you got yourself a new avatar, were you tired of being the clown fish, can’t brain?

You see a code with pop invoked 8 times, but don't bother calling it?
:D

[kleinman]

This is fun, isn't it?
Sure it’s fun, but a bit unfair for you. You have taken a ridiculous, mathematically impossible position that multiple selection pressures accelerate evolution with no real examples of your silly graph while I have the results of a peer reviewed and published model of mutation and selection which supports my position that multiple selection pressures slow the evolutionary process. In addition I have a massive number of citations which give empirical support to my contention. It is really unfair to you poor mathematically challenged evolutionarians.
You see a code with pop invoked 8 times, but don't bother calling it?
I don’t need to, ev and the huge number of citations which I have posted have already made the theory of evolution go pop. Hey joobz, do you remember you said evolution could not be stopped, read the following citation.

http://aac.asm.org/cgi/content/full/50/3/975 (http://aac.asm.org/cgi/content/full/50/3/975)
Hypermutable Pseudomonas aeruginosa strains are found with high frequency in the lungs of patients with chronic infections and are associated with high antibiotic resistance rates. The in vivo consequences of hypermutation for treatment in a mouse model of lung infection using strain PAO1 and its hypermutable derivative PAO mutS are investigated. Groups of 30 mice were treated for 3 days with humanized regimens of ciprofloxacin (CIP), tobramycin (TOB), CIP plus TOB, or placebo, and mortality, total lung bacterial load, and 4x- and 16x-MIC mutants were recorded. The rates of mutation and the initial in vivo frequencies of mutants (at the onset of treatment) were also estimated and the in vitro- and in vivo-selected mutants characterized. Since both strains had identical MICs, the same pharmacokinetic/pharmacodynamic (PK/PD) parameters were obtained: area under the 24-h concentration-time curve (fAUC)/MIC = 385 for CIP and maximum concentration of drug in serum (fCmax)/MIC = 19 for TOB. Despite adequate PK/PD parameters, persistence of high bacterial numbers and amplification (50,000-fold) of resistant mutants (MexCD-OprJ hyperexpression) were documented with CIP treatment for PAO mutS, in contrast to complete resistance suppression for PAO1 (P < 0.01), showing that conventional PK/PD parameters may not be applicable to infections by hypermutable strains. On the other hand, the efficacy of TOB monotherapy in terms of mortality reduction and bacterial load was very low regardless of the strain but not due to resistance development, since mutants were not selected for PAO1 and were only modestly amplified for PAO mutS. Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAO mutS (P < 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutable P. aeruginosa using appropriate combined regimens.
This really is fun.

[kjkent1]

Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAOmutS (P < 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutable P. aeruginosa using appropriate combined regimens.This really is fun.Well, I hate to spoil your fun, but I'm gonna hand you your ass...again.

Because, the follow up to the study that you quote above shows a remarkably different result, and it completely falsifies your hypothesis:

Mechanisms and Dynamics of In Vitro and In Vivo Resistance Development to Single or Combined Antipseudomonal Agents: Influence of High Mutation Rates.

Plasencia V, Borrell N, Maciá MD, Moya B, Pérez JL, Oliver A.
Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta. Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS). Palma de Mallorca, Spain.

We studied the mechanisms and dynamics of resistance development to ceftazidime (CAZ) alone or combined with tobramycin (TOB) or ciprofloxacin (CIP) in vitro and in vivo (mouse model of lung infection using humanized antibiotic regimens). Strains PAO1 and its hypermutable derivative PAODelta mutS were used, and the results were compared with those previously obtained for CIP, TOB and CIP+TOB under the same conditions. An important (200-fold) amplification of resistant mutants was documented in mice infected by PAODelta mutS under CAZ treatment compared to placebo, whereas the median number of resistant mutants was below the detection limits for mice infected by PAO1. These results were intermediate between the high amplification of ciprofloxacin (50.000-fold) and the low amplification of tobramycin (10-fold). All single CAZ resistant mutants selected in vitro or in vivo hyperproduced AmpC. On the other hand, the 3 combinations studied were found to be highly effective in the prevention of in vivo resistance development in mice infected with PAODelta mutS, although the highest therapeutic efficacy (in terms of mortality and total bacterial load reduction) compared to the individual regimens was obtained with CIP+TOB, and the lowest with CAZ+CIP. Nevertheless, resistant mutants to the 3 combinations tested were readily selected in vitro for PAODelta mutS (mutation rates from 1.2X10(-9) to 5.8X10(-11)) but not for PAO1, highlighting the potential risk for antimicrobial resistance development associated with the presence of hypermutable strains, even when using combined therapy. All 5 independent CAZ-TOB PAODelta mutS double mutants studied presented the same resistance mechanism (AmpC hyperproduction + an aminoglycoside resistance mechanism not related to MexXY), whereas 4 different combinations of resistance mechanisms were documented in the 5 CAZ-CIP double mutants.
PMID: 17470655 [PubMed - as supplied by publisher]

Mighty kleinman has struck out.

[quixotecoyote]

]I don’t need to, ev...



WHOA. Hold it right there. You've been trumpeting about ev being a computer model to disprove evolution, but you don't even know how to declare a constant to run Dr. A's experiment? I can't believe it! You are actually even more inept than I previously imagined. How on Earth do you expect anyone to take you at all seriously when you just demonstrated complete incompetence in the primary area you were claiming as evidence?

[joobz]

WHOA. Hold it right there. You've been trumpeting about ev being a computer model to disprove evolution, but you don't even know how to declare a constant to run Dr. A's experiment? I can't believe it! You are actually even more inept than I previously imagined. How on Earth do you expect anyone to take you at all seriously when you just demonstrated complete incompetence in the primary area you were claiming as evidence?
Yes, this was the same feeling I had when Kleinman claimed to have taught thermodynamics. After this assertion, he went on to provide kinetic arguments that he claimed were "thermodynamic". Based upon the usage he was invoking, such a claim was the epitome of foolishness.

Now, his claims of having done research in heat transfer computational modeling are even more circumspect. The simple ability to run someone else's code is beyond him. The ability understand probability theory is beyond him. The ability to present any mathematical argument to support his case is beyond him.

I wonder why he would think anyone would believe the stuff he says.

[quixotecoyote]

Plus the last two citations he posted were shown by myself and kjent1 to prove the exact opposite position than he was claiming. I'm sure others have pointed out his previous citation issues. I'm suspicious that anyone could hurt their own case so much on purpose.

kleinman, are you for real?

[Belz...]

The theory of evolution by mutation and selection is mathematically impossible.

No.

There. I've disproved your claim.

[Mr. Scott]

Dr. Kleinman, in your opinion, given that the human spine evolved from supporting a four-legged creature to its present day upright stance with its resulting issues in medical diagnosis and treatment, is this an example of micro evolution or macro evolution?

http://forums.randi.org/imagehosting/673646b07a2d095a2.jpg

[Anacoluthon64]

Now Adequate finally will try to post some nonsense code.

…

Adequate thinks he can fool people with this nonsense so let’s see what happens when we run this code fragment through a Pascal compiler.

…

The numbers above correspond to the line numbers in Adequate’s code fragment with errors in them. So not only is Adequate afraid to post his entire code, the code fragment he does post has syntax errors, he fails to describe what his selection conditions are. Adequate, you are completely wrong about how mutation and selection actually works and your error filled code fragment is proof of nothing other than you are incompetent in the mathematics of mutation and selection.Half a tonne of tuppenny lies,
Half a tonne of "cheesel."
That's the way delusion goes,
pop! goes the weasel.

kleinman, I'm afraid you're the naif who just lost Pascal's Wager.

'Luthon64

[Taffer]

Wow, he's still at it.

A quick browse of this page shows me that he is still equating evolution with the emergence of a particular trait.

Do others agree that it's time for a Frank and Earnest discussion?

[kleinman]

Breach of civility removed. Please keep it civil and polite, kleinman.

Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAOmutS (P < 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutable P. aeruginosa using appropriate combined regimens. Well, I hate to spoil your fun, but I'm gonna hand you your ass...again.
So how is lita’ gator going to “hand you your ass…again”? Why, he is going to post from an article he doesn’t understand. Here is his post.
We studied the mechanisms and dynamics of resistance development to ceftazidime (CAZ) alone or combined with tobramycin (TOB) or ciprofloxacin (CIP) in vitro and in vivo (mouse model of lung infection using humanized antibiotic regimens). Strains PAO1 and its hypermutable derivative PAODelta mutS were used, and the results were compared with those previously obtained for CIP, TOB and CIP+TOB under the same conditions. An important (200-fold) amplification of resistant mutants was documented in mice infected by PAODelta mutS under CAZ treatment compared to placebo, whereas the median number of resistant mutants was below the detection limits for mice infected by PAO1. These results were intermediate between the high amplification of ciprofloxacin (50.000-fold) and the low amplification of tobramycin (10-fold). All single CAZ resistant mutants selected in vitro or in vivo hyperproduced AmpC. On the other hand, the 3 combinations studied were found to be highly effective in the prevention of in vivo resistance development in mice infected with PAODelta mutS, although the highest therapeutic efficacy (in terms of mortality and total bacterial load reduction) compared to the individual regimens was obtained with CIP+TOB, and the lowest with CAZ+CIP. Nevertheless, resistant mutants to the 3 combinations tested were readily selected in vitro for PAODelta mutS (mutation rates from 1.2X10(-9) to 5.8X10(-11)) but not for PAO1, highlighting the potential risk for antimicrobial resistance development associated with the presence of hypermutable strains, even when using combined therapy. All 5 independent CAZ-TOB PAODelta mutS double mutants studied presented the same resistance mechanism (AmpC hyperproduction + an aminoglycoside resistance mechanism not related to MexXY), whereas 4 different combinations of resistance mechanisms were documented in the 5 CAZ-CIP double mutants.
What lita’ gator doesn’t understand is that Pseudomonas can become resistant to particular antibiotic classes without ever being exposed to those classes. How does pseudomonas accomplish this? It is not by mutation and selection. Here’s a portion from a paper where these authors explain how Pseudomonas accomplishes the acquisition of resistance to particular antibiotic without being subjected to these selection pressures.
http://jac.oxfordjournals.org/cgi/content/full/48/4/553 (http://jac.oxfordjournals.org/cgi/content/full/48/4/553)
Emergence of resistance during therapy has been repeatedly associated with poor clinical outcome in patients with P. aeruginosa infections.1,7 In the case reported here, ciprofloxacin monotherapy failed to eradicate the ongoing infection and led to the rapid emergence of a gyrB/overexpressed MexAB-OprM double mutant. This mutant was not only strongly resistant to fluoroquinolones (128 x MIC of ciprofloxacin), but also no longer susceptible to the antipseudomonal ß-lactams ticarcillin (16 x MIC), cefsulodin and aztreonam. The MexAB-OprM system is indeed known to mediate resistance to numerous structurally unrelated antibiotics, including ß-lactams (except imipenem), quinolones, tetracyclines and chloramphenicol.8 The bad clinical response under ciprofloxacin monotherapy prompted medical staff to initiate a new treatment with ceftazidime (100 mg/kg/day) and amikacin (15 mg/kg/day), which rapidly cured the patient of his infection.

A recent cohort study of 271 patients with P. aeruginosa infections showed that fluoroquinolone resistance tends to develop quite frequently (8%) during ciprofloxacin treatment.7 In the case of our patient, it could be tempting to draw the conclusion that fluoroquinolone monotherapy is more prone than combination therapy to select multidrug-resistant mutants in vivo and thus is not a valid option in P. aeruginosa infections. However, emergence of MexAB-OprM mutants has been observed in patients treated with ß-lactams and fluoroquinolones, ß-lactams and aminoglycosides, or fluoroquinolones and aminoglycosides.5 Similarly, in another study, combination therapy with aminoglycosides did not appear to prevent the emergence of resistance to ciprofloxacin.7

Overexpression of the multidrug efflux system MexAB-OprM3,5,8,9 as well as occurrence of mutations in gyrB2 are known to confer moderate resistance to fluoroquinolones (e.g. MIC of ciprofloxacin <4 mg/L). Importantly, our observation demonstrates that acquisition of both mechanisms may provide clinical strains with a high degree of fluoroquinolone resistance and lead to clinical failure. Other examples of cumulative effects between efflux pumps (MexAB-OprM or MexCD-OprJ) and target alterations (gyrA, parC) have been reported recently.3,10 Thus, it becomes more and more evident that high-level resistance to fluoroquinolones in P. aeruginosa not only results from sequential acquisition of mutations in the target genes gyrA, gyrB and parC, but may also be associated with overexpression of efflux pumps.
Lita’ gator, what you don’t understand about these papers is that there are two mechanisms of developing resistance that Pseudomonas uses. One is the mutation and selection process and the other is the overexpression of efflux pumps. The mutation selection process of target genes in Pseudomonas evolves resistance to each selection process (antibiotic) individually while the overexpression of efflux pumps can give resistance to multiple antibiotics that Pseudomonas has never been exposed to. Once again, lita’ gator, your objection is overruled by the facts.
I don’t need to, ev...]WHOA. Hold it right there. You've been trumpeting about ev being a computer model to disprove evolution, but you don't even know how to declare a constant to run Dr. A's experiment? I can't believe it! You are actually even more inept than I previously imagined. How on Earth do you expect anyone to take you at all seriously when you just demonstrated complete incompetence in the primary area you were claiming as evidence?
Really, do you want me to show you my credentials as a computer programmer? I have already posted my academic credentials including my PhD in mechanical engineering. I have also indicated on this thread to those interested where they can find my PhD thesis which was based on a computer model solving a nonlinear partial differential equation. I have also published computer solutions to other nonlinear partial differential equations. I have taught graduate level engineering courses that included the use of computer solutions to mathematical equations. In addition, I have years of commercial experience working with complex computer simulations used in building real systems. Noticed I didn’t make you wade through now 128 pages of this thread for this information even though it was already in there. But when you asked Adequate the following:
Hey Dr. A, spare me from having to go through the last 125 pages hunting. Where did the data points for your graph come from?
What did Adequate give you? He gave you a code fragment that won’t compile. Ev is a mature computer model that Dr Schneider has been working on for more than 20 years. He has published the results in a reputable journal and the full executable code is available online. It is not some stupid bluff that Adequate is trying to use to pull the blinds over naïve eyes like yours.
WHOA. Hold it right there. You've been trumpeting about ev being a computer model to disprove evolution, but you don't even know how to declare a constant to run Dr. A's experiment? I can't believe it! You are actually even more inept than I previously imagined. How on Earth do you expect anyone to take you at all seriously when you just demonstrated complete incompetence in the primary area you were claiming as evidence?Yes, this was the same feeling I had when Kleinman claimed to have taught thermodynamics. After this assertion, he went on to provide kinetic arguments that he claimed were "thermodynamic". Based upon the usage he was invoking, such a claim was the epitome of foolishness.

Now, his claims of having done research in heat transfer computational modeling are even more circumspect. The simple ability to run someone else's code is beyond him. The ability understand probability theory is beyond him. The ability to present any mathematical argument to support his case is beyond him.

I wonder why he would think anyone would believe the stuff he says.
So, let’s see. There are only two people posting on this thread using their real names, Paul and myself. Delphi has revealed his real name but does not post under that name. You can look into my background which some of you have. Now you cowardly evolutionarians post under pseudonyms which is appropriate for a pseudoscientific theory. Joobz claims to be a PhD in chemical engineering and is a professor at a university. Post your real name and the university you teach at. I wonder what your fellow professors would say about this.
Envision a system of millions of forming and destructive chemical reactions. Now, envision that intermediates of there reactions associate through non-covalent means and that this complex becomes protected against the destructive reactive pathway, perhaps by a reversible precipitation. These new complexes result in a localized increased of new chemical species. These chemical species then progress in a new series of reaction... that is what I mean through cooperative means. I acknowledge this is complete speculation, but well within the range of chemical possibility. As long as there was enough free energy for these reaction to occur.
:dl:
Hey joobz, if enough sunlight hits lead, does it turn into gold?
The theory of evolution by mutation and selection is mathematically impossible.No.

There. I've disproved your claim.
I must admit your argument is concise Belz. Too bad it doesn’t have any mathematical or empirical basis.
Dr. Kleinman, in your opinion, given that the human spine evolved from supporting a four-legged creature to its present day upright stance with its resulting issues in medical diagnosis and treatment, is this an example of micro evolution or macro evolution?
Pussycat, the discussion topic for this thread is the mathematics of mutation and selection. The central issue is the mathematical behavior of the ev computer simulation of random point mutations and natural selection and whether what it shows is realistic and has captured the essentials of the evolutionary process by mutation and selection. When you evolutionarians finally admit how mutation and selection actually works, we can go on to other discussion topics. This is probably going to take a long time because you mathematically challenged evolutionarians are having a hard time understanding how mutation and selection actually works. I don’t blame you for trying to change the subject (is that moving the goalposts?) since mutation and selection is the core principle of your theory and it simply does not work like you allege. Pussycat, why don’t you post a citation which shows that multiple selection pressures accelerate evolution?

Don’t you think it is time to post a citation which shows how mutation and selection actually works? That is that multiple selection pressures slow down the evolutionary process profoundly. So here is another example which shows this.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1692562 (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1692562)
Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection. Use of combinations of antimalarials that do not share the same resistance mechanisms will reduce the chance of selection because the chance of a resistant mutant surviving is the product of the per parasite mutation rates for the individual drugs, multiplied by the number of parasites in an infection that are exposed to the drugs. Artemisinin derivatives are particularly effective combination partners because (i) they are very active antimalarials, producing up to 10,000-fold reductions in parasite biomass per asexual cycle; (ii) they reduce malaria transmissibility; and (iii) no resistance to these drugs has been reported yet. There are good arguments for no longer using antimalarial drugs alone in treatment, and instead always using a combination with artemisinin or one of its derivatives.
Now if you listen to Adequate’s silly evolutionarian bluff, you could say there is a good argument for using antimalarial drugs as monotherapy, which is multiple selection pressures accelerate evolution. Of course the mathematical and empirical evidence says the exact opposite but don’t let that keep you evolutionarians from believing your strange and unscientific and mathematically impossible mythology.

[kleinman]

A quick browse of this page shows me that he is still equating evolution with the emergence of a particular trait.
Wow, what a powerful argument. Emergence of a particular trait by mutation and selection is not evolution. So now we have the theory of evolution by mutation and selection and we have the theory of emergence by mutation and selection. Taffer, do you want to give us an example where multiple selection pressures accelerate evolution?

[quixotecoyote]

Why should she? We've already highlighted two that you gave us.

[Belz...]

I must admit your argument is concise Belz. Too bad it doesn’t have any mathematical or empirical basis.

WARNING WARNING. IRONY OVERLOAD. EMERGENCY SHUTDOWN.

:id:

Too late. Damn.

[Dr Adequate]

Wow, what a powerful argument. Emergence of a particular trait by mutation and selection is not evolution We can all see that he didn't say that, so we all know that you're lying.

[Dr Adequate]

Breach of civility removed. Please keep it civil and polite, kleinman.


So how is lita’ gator going to “hand you your ass…again”? Why, he is going to post from an article he doesn’t understand. Here is his post.

What lita’ gator doesn’t understand is that Pseudomonas can become resistant to particular antibiotic classes without ever being exposed to those classes. How does pseudomonas accomplish this? It is not by mutation and selection. Here’s a portion from a paper where these authors explain how Pseudomonas accomplishes the acquisition of resistance to particular antibiotic without being subjected to these selection pressures.
http://jac.oxfordjournals.org/cgi/content/full/48/4/553 (http://jac.oxfordjournals.org/cgi/content/full/48/4/553)

Lita’ gator, what you don’t understand about these papers is that there are two mechanisms of developing resistance that Pseudomonas uses. One is the mutation and selection process and the other is the overexpression of efflux pumps. The mutation selection process of target genes in Pseudomonas evolves resistance to each selection process (antibiotic) individually while the overexpression of efflux pumps can give resistance to multiple antibiotics that Pseudomonas has never been exposed to. Once again, lita’ gator, your objection is overruled by the facts.

Really, do you want me to show you my credentials as a computer programmer? I have already posted my academic credentials including my PhD in mechanical engineering. I have also indicated on this thread to those interested where they can find my PhD thesis which was based on a computer model solving a nonlinear partial differential equation. I have also published computer solutions to other nonlinear partial differential equations. I have taught graduate level engineering courses that included the use of computer solutions to mathematical equations. In addition, I have years of commercial experience working with complex computer simulations used in building real systems. Noticed I didn’t make you wade through now 128 pages of this thread for this information even though it was already in there. But when you asked Adequate the following:

What did Adequate give you? He gave you a code fragment that won’t compile. Ev is a mature computer model that Dr Schneider has been working on for more than 20 years. He has published the results in a reputable journal and the full executable code is available online. It is not some stupid bluff that Adequate is trying to use to pull the blinds over naïve eyes like yours.

So, let’s see. There are only two people posting on this thread using their real names, Paul and myself. Delphi has revealed his real name but does not post under that name. You can look into my background which some of you have. Now you cowardly evolutionarians post under pseudonyms which is appropriate for a pseudoscientific theory. Joobz claims to be a PhD in chemical engineering and is a professor at a university. Post your real name and the university you teach at. I wonder what your fellow professors would say about this.

:dl:
Hey joobz, if enough sunlight hits lead, does it turn into gold?

I must admit your argument is concise Belz. Too bad it doesn’t have any mathematical or empirical basis.

Pussycat, the discussion topic for this thread is the mathematics of mutation and selection. The central issue is the mathematical behavior of the ev computer simulation of random point mutations and natural selection and whether what it shows is realistic and has captured the essentials of the evolutionary process by mutation and selection. When you evolutionarians finally admit how mutation and selection actually works, we can go on to other discussion topics. This is probably going to take a long time because you mathematically challenged evolutionarians are having a hard time understanding how mutation and selection actually works. I don’t blame you for trying to change the subject (is that moving the goalposts?) since mutation and selection is the core principle of your theory and it simply does not work like you allege. Pussycat, why don’t you post a citation which shows that multiple selection pressures accelerate evolution?

Don’t you think it is time to post a citation which shows how mutation and selection actually works? That is that multiple selection pressures slow down the evolutionary process profoundly. So here is another example which shows this.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1692562 (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1692562)

Now if you listen to Adequate’s silly evolutionarian bluff, you could say there is a good argument for using antimalarial drugs as monotherapy, which is multiple selection pressures accelerate evolution. Of course the mathematical and empirical evidence says the exact opposite but don’t let that keep you evolutionarians from believing your strange and unscientific and mathematically impossible mythology. You ask us whether we wish you to show us your "credentials as a computer programmer".

You have done so, and are doing so.

Are we to gather from your whining about "a code fragment that won’t compile" that you still don't know how to declare constants in Pascal?

Poor kleinman.

[Paul C. Anagnostopoulos]

So what? Each of the individual selection conditions, evolving the binding sites, eliminating the spurious binding in the genes and eliminating the spurious binding outside the binding site region easily evolve on the longer genomes when done individually.
The individual selection condition is not eliminating spurious bindings! There are no real bindings evolving, so there can't be spurious ones. It is simply eliminating bindings altogether, which is a completely different thing.


It is only when the model tries to evolve all three conditions simultaneously that the evolutionary process is profoundly slowed.
Is that because three simultaneous conditions are theoretically slower, or because three simultaneous conditions are evolving something completely different from the individual conditions? For example, I wonder if the simultaneous conditions are evolving the elimination of spurious bindings?


I haven’t ignored your concept of Rcapacity; I have shown you that it is not real.
So you think Rsequence can approach Rfrequency even if the binding sites are too narrow to distinguish them from all the other sites. The fact that you believe this makes me think you do not understand what is evolving in Ev.

~~ Paul

[kleinman]

Wow, what a powerful argument. Emergence of a particular trait by mutation and selection is not evolution.We can all see that he didn't say that, so we all know that you're lying.
Let’s repeat for everyone what Taffer said.
A quick browse of this page shows me that he is still equating evolution with the emergence of a particular trait.
Adequate, we all know what a twisted convoluted mind you have, after all here is how you think mutation and selection works.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
So are you talking about evolution or emergence silly evolutionarian? Give us an example of multiple selection pressures accelerating either emergence of resistance or evolution. You can’t because your graph is nonsense and mutation and selection does not work the way you allege. Whether you want to call it emergence of resistance or evolution, mutation and selection slows profoundly when you have multiple selection pressures.
So what? Each of the individual selection conditions, evolving the binding sites, eliminating the spurious binding in the genes and eliminating the spurious binding outside the binding site region easily evolve on the longer genomes when done individually.The individual selection condition is not eliminating spurious bindings! There are no real bindings evolving, so there can't be spurious ones. It is simply eliminating bindings altogether, which is a completely different thing.
Paul, you understand how your model works better than this. When your weight matrix finds a match to within the threshold you have located a binding site. When you set the two spurious binding conditions to zero, sequences of bases will evolve at their proper locations that match the weight matrix within the threshold limit. You are trying to squirm out of what your model shows because this was not your original intention. What your model in fact shows is how multiple selection conditions affects evolution by mutation and selection. It just so happens that this fits the empirical data (I have another example posted below) very nicely. It also fits Delphi’s reference to fitness landscape in Wikipedia. Your program shows exactly how the mutation selection process works but you have gone into denial because it does not fit your belief system.
It is only when the model tries to evolve all three conditions simultaneously that the evolutionary process is profoundly slowed.Is that because three simultaneous conditions are theoretically slower, or because three simultaneous conditions are evolving something completely different from the individual conditions? For example, I wonder if the simultaneous conditions are evolving the elimination of spurious bindings?
Dr Schneider defined a mathematically explicit selection condition with his weight matrix. Spurious binding occurs when a sequence of bases is matched by the weight matrix where a binding site should not occur. It doesn’t matter whether the spurious binding condition is applied as an individual selection condition or in combination with the other selection conditions. A match is counted as a mistake when the weight matrix finds a match where it should not occur (when that selection condition is nonzero). The three simultaneous selection conditions evolve sequence of bases which find matches to the weight matrix where binding sites are expected to be found and different sequences of bases that don’t match the weight matrix where binding sites are not expected to be found. If you did your coding properly (and I think you did), your model will eliminate spurious binding when all three selection conditions are applied (and the genome is short enough to allow the model to converge).
I haven’t ignored your concept of Rcapacity; I have shown you that it is not real.So you think Rsequence can approach Rfrequency even if the binding sites are too narrow to distinguish them from all the other sites. The fact that you believe this makes me think you do not understand what is evolving in Ev.
Paul, I think that the weight matrix can always find sequence of bases that give matches no matter how large or small the width of the binding site is and no matter how long or short the genome is. It is only when you try to eliminate spurious binding and evolve the binding sites simultaneously that the model has trouble converging. The simultaneous selection conditions confound the selection process. As you lengthen the genome in the model, you lengthen the non-binding site region of the genome. It is mistakes in this region which ultimately slow and then stop the convergence of your model. Large binding site widths give you a little reprieve from this effect because it keeps down the number of mistakes in the non-binding site region but ultimately, as you lengthen the genome (and the non-binding site region), errors in this region slow and then stop convergence of the model.

Now Paul, you can ask the following question. Do errors (spurious binding) in the non-binding region have any relationship to reality? While you are pondering this, ponder the following citation as well.

http://www.natap.org/2006/ResisWksp/ResisWksp_02.htm (http://www.natap.org/2006/ResisWksp/ResisWksp_02.htm)
Abstract
BACKGROUND: A-848837 is a novel specific inhibitor of the HCV RNA-dependent RNA polymerase with excellent PK in animals. Given the high mutation and replication rate of HCV, it is likely that mutant viruses with decreased susceptibility to antiviral regimens will emerge during therapy. Understanding the in vitro resistance profiles of the HCV inhibitors is therefore of considerable interest. (This drug is a prototype for a potential future Abbott polymerase inhibitor drug).

METHODS: The anti-HCV activity of A-848837 was determined in HCV replicon cells by the reduction of HCV RNA. HCV replicon colonies resistance to the inhibitors were selected by treating the HCV subgenomic 1b-N replicon cells with A-848837 at a concentration 10 times above its corresponding IC50 in the presence of neomycin. Genotypes of the resistant colonies were determined by sequencing the NS5B polymerase gene. Individual mutations were introduced into a luciferase-expressing replicon by site-directed mutagenesis. The susceptibility of the mutants was evaluated by a trans-replication assay.

RESULTS: A-848837 displayed potent activity in the HCV replicon tissue culture with an IC50 of 2 and 4 nM against genotypes 1a and 1b, respectively (not active against other genotypes). Following selection with A-848837, replicon colonies were found to be approximately 33- to >800-fold resistant to A-848837. Each colony found one to three of the following mutations: G46A, S368T, I392F, M414T, Y448H, Q514R, G554D, D559G, and Y586C within NS5B polymerase gene. Molecular clones containing the above amino acid substitutions displayed 4- to 255-fold reduced susceptibility to A-848837. In contrast, all mutants retained full susceptibility to the polymerase inhibitor thiophene-2-carboxylic acid (Shire polymerase inhibitor), HCV protease inhibitor, and interferon (IFN). Furthermore, combination of A-848837 with IFN or protease inhibitor produced an additive to synergistic effect in replicon cells. All mutants except I392F exhibited reduced replication capacity compared to the wild-type replicon.

CONCLUSION: This study suggested that single amino acid substitutions at any of several positions could result in reduced susceptibility to A-848837. However, combination of this inhibitor with IFN or protease inhibitor may be synergistic in controlling replication.
and
Selection and characterization of mutations conferring resistance to a HCV RNA dependent RNA polymerase inhibitor A-848837 in vitro"]The combination of 20 times EC50 IFN plus 20 times EC50 A-848837 displayed an apparent synergistic effect. Simultaneous treatment with both drugs was able to reduce RNA to an undetectable level after passage 4. [/COLOR]

No resistant colonies were identified when neomycin was added at passage 6, indicating that replicon cells were cured by the combination treatment.
There is so much evidence how mutation and selection actually works, I find it amazing that evolutionarians have so little understanding of this process. Multiple selection pressures slow evolution. That is what the mathematics of ev shows, that is what Delphi’s Wikipedia reference to the fitness landscape shows and that is what the massive amount of empirical evidence of mutation and selection shows.

[kjkent1]

Lita’ gator, what you don’t understand about these papers is that there are two mechanisms of developing resistance that Pseudomonas uses. One is the mutation and selection process and the other is the overexpression of efflux pumps. The mutation selection process of target genes in Pseudomonas evolves resistance to each selection process (antibiotic) individually while the overexpression of efflux pumps can give resistance to multiple antibiotics that Pseudomonas has never been exposed to.Unlike you, Alan, I freely concede when I am in error and I graciously accept new knowledge. So the issue of efflux pump overexpression is quite interesting.

However, there is no evidence that my posted article attributed the subject organism's resistance to anything other than mutation and selection. Thus, you are inventing a theory to avoid an otherwise inescapable finding which falsifies your theory.

If the authors of my posted article found that efflux pump overexpression was the cause of the resistance, then they would have so stated. Instead, they referred to the risk of resistance associated with "hypermutable" organisms -- a clear indicator of mutation and natural selection -- not efflux pump overexpression.

[krazyKemist]

What lita’ gator doesn’t understand is that Pseudomonas can become resistant to particular antibiotic classes without ever being exposed to those classes. How does pseudomonas accomplish this? It is not by mutation and selection. Here’s a portion from a paper where these authors explain how Pseudomonas accomplishes the acquisition of resistance to particular antibiotic without being subjected to these selection pressures.

Lita’ gator, what you don’t understand about these papers is that there are two mechanisms of developing resistance that Pseudomonas uses. One is the mutation and selection process and the other is the overexpression of efflux pumps. The mutation selection process of target genes in Pseudomonas evolves resistance to each selection process (antibiotic) individually while the overexpression of efflux pumps can give resistance to multiple antibiotics that Pseudomonas has never been exposed to. Once again, lita’ gator, your objection is overruled by the facts.

Ahhh... Finally. We are making some progress it seems. You have just admitted (with the usual boring, frustrated-teenager insults) that adaptation (resistance is an adaptation, right ? You've used it that way quite freely when we were talking about cancer therapy) may be the product of something else than a new mutation. As in "overexpression of already existing genes". And that a single new feature/gene may allow the adaptation of an organism to several antibiotics/selection pressures.

But doesn't that contradict all the importance you are giving to ev in explaining anything and everything about evolution, life and medicinal research ? Remember the assumptions you are making when declaring that ev describes exactly how evolution and adaptation works. Don't you think that what you've discussed until now is a terrible oversimplification of how adaptation works ? Again, honestly ?

And to answer your comment about helicase and replicase, consider this : what you are doing is applying an ID/creationist belief to the theory of evolution. That belief is purpose (as in "what was the purpose of helicase before it was integrated in the DNA replicating system ?"). You seem to have the same problem with Taffer's statement about believing evolution being about developping a particular (predestined, if you prefer) trait. It is not. It's about following the laws of nature to generate complexity. What you are actually telling is that a lake is formed because the water molecules like that particular spot, and want to go there. What we're saying is that the lake formed because there's a depression in the ground allowing the water to pool there. The latter explanation uses only laws of nature (science), the first a water spirit (religion).

I remember having the exact same discussion with my two creationist friends, whom were considerably more civil than you are. When I pointed this out to them, they could only answer me back, "but don't you need humans (and by extension, your life) to have a purpose ?"

the Kemist

[joobz]

Breach of civility removed. Please keep it civil and polite, kleinman.
So, let’s see. There are only two people posting on this thread using their real names, Paul and myself. Delphi has revealed his real name but does not post under that name. You can look into my background which some of you have. Now you cowardly evolutionarians post under pseudonyms which is appropriate for a pseudoscientific theory. Joobz claims to be a PhD in chemical engineering and is a professor at a university. Post your real name and the university you teach at. I wonder what your fellow professors would say about this.

:dl:
Hey joobz, if enough sunlight hits lead, does it turn into gold?
What's your point? I've shown this thread to some of them, and they see nothing wrong with the context of the original posting.

Although, they got a big laugh at...
your coding blunders
your definition of thermodynamics
your application of a model
Your stupid attempt at probability theory


ETA: I'll post again when I see kleinman make another NEW, completely foolish mistake.

[Paul C. Anagnostopoulos]

Paul, you understand how your model works better than this. When your weight matrix finds a match to within the threshold you have located a binding site. When you set the two spurious binding conditions to zero, sequences of bases will evolve at their proper locations that match the weight matrix within the threshold limit. You are trying to squirm out of what your model shows because this was not your original intention.
And every other position will also bind to the gene. Do you agree that this is not the same function as the one that evolves when all three pressures are active?


Dr Schneider defined a mathematically explicit selection condition with his weight matrix. Spurious binding occurs when a sequence of bases is matched by the weight matrix where a binding site should not occur. It doesn’t matter whether the spurious binding condition is applied as an individual selection condition or in combination with the other selection conditions.
Yes it does. A match can only be "spurious" if there are other matches that are not spurious. If there is only one pressure being applied, then there are no spurious bindings. There are simply bindings or no bindings. The point of this semantic argument is that the same function is not evolving when only one pressure is being applied.


The three simultaneous selection conditions evolve sequence of bases which find matches to the weight matrix where binding sites are expected to be found and different sequences of bases that don’t match the weight matrix where binding sites are not expected to be found. If you did your coding properly (and I think you did), your model will eliminate spurious binding when all three selection conditions are applied (and the genome is short enough to allow the model to converge).
Correct. And it will not do so when only one selection condition is applied.


Paul, I think that the weight matrix can always find sequence of bases that give matches no matter how large or small the width of the binding site is and no matter how long or short the genome is. It is only when you try to eliminate spurious binding and evolve the binding sites simultaneously that the model has trouble converging.
This is because Rcapacity only matters when you're applying all three pressures. Otherwise you are not distinguishing binding sites from other positions.


Now Paul, you can ask the following question. Do errors (spurious binding) in the non-binding region have any relationship to reality?
Yes, they do. The entire mechanism of gene expression control depends on it.

~~ Paul

[Belz...]

Am I the only one who thinks that Klein is spamming, here ?

[Apathia]

Am I the only one who thinks that Klein is spamming, here ?

Earlier I suggested he was being deliberately annoying to the extent of troll behavior.
However, Paul assures us of Dr. K's total sincerity.
I still check in on it with a morbid fascination.

[kleinman]

So you mathematically challenged evolutionarians are still having difficulty shedding light on the mathematics of mutation and selection. Since you are having this difficulty understanding what ev shows mathematically, that is multiple selection pressures profoundly slow the evolutionary process, I will post more empirical examples which show this. But first, your interrogatories.
Lita’ gator, what you don’t understand about these papers is that there are two mechanisms of developing resistance that Pseudomonas uses. One is the mutation and selection process and the other is the overexpression of efflux pumps. The mutation selection process of target genes in Pseudomonas evolves resistance to each selection process (antibiotic) individually while the overexpression of efflux pumps can give resistance to multiple antibiotics that Pseudomonas has never been exposed to.Unlike you, Alan, I freely concede when I am in error and I graciously accept new knowledge. So the issue of efflux pump overexpression is quite interesting.

However, there is no evidence that my posted article attributed the subject organism's resistance to anything other than mutation and selection. Thus, you are inventing a theory to avoid an otherwise inescapable finding which falsifies your theory.

If the authors of my posted article found that efflux pump overexpression was the cause of the resistance, then they would have so stated. Instead, they referred to the risk of resistance associated with "hypermutable" organisms -- a clear indicator of mutation and natural selection -- not efflux pump overexpression.
If that is the case lita’ gator; when are you going to so graciously accept the mathematical and empirical fact that multiple selection pressures accelerate evolution? The evidence is overwhelming; I’ll post a couple more citations below.
What lita’ gator doesn’t understand is that Pseudomonas can become resistant to particular antibiotic classes without ever being exposed to those classes. How does pseudomonas accomplish this? It is not by mutation and selection. Here’s a portion from a paper where these authors explain how Pseudomonas accomplishes the acquisition of resistance to particular antibiotic without being subjected to these selection pressures.

Lita’ gator, what you don’t understand about these papers is that there are two mechanisms of developing resistance that Pseudomonas uses. One is the mutation and selection process and the other is the overexpression of efflux pumps. The mutation selection process of target genes in Pseudomonas evolves resistance to each selection process (antibiotic) individually while the overexpression of efflux pumps can give resistance to multiple antibiotics that Pseudomonas has never been exposed to. Once again, lita’ gator, your objection is overruled by the facts.Ahhh... Finally. We are making some progress it seems. You have just admitted (with the usual boring, frustrated-teenager insults) that adaptation (resistance is an adaptation, right ? You've used it that way quite freely when we were talking about cancer therapy) may be the product of something else than a new mutation. As in "overexpression of already existing genes". And that a single new feature/gene may allow the adaptation of an organism to several antibiotics/selection pressures.
Now listen krazy, I have to address my comments to the intellectual level of the audience. So let’s consider the Pseudomonas efflux pump. This pump has the capability to pump out a variety of chemically unique and unrelated toxins. Why don’t the Pseudomonas bacteria maintain this pump all the time in its population? Do you think that humans subjecting these bacteria to antibiotics are the first time Pseudomonas ever was subjected to a toxin?
But doesn't that contradict all the importance you are giving to ev in explaining anything and everything about evolution, life and medicinal research ? Remember the assumptions you are making when declaring that ev describes exactly how evolution and adaptation works. Don't you think that what you've discussed until now is a terrible oversimplification of how adaptation works ? Again, honestly ?
Oh, ev doesn’t explain everything about evolution, but it does explain something about the mathematics of mutation and selection. The things that it does show is what happens when you have multiple selection pressures, profoundly slows the evolutionary process. It also shows what happens to the rate of evolution as you lengthen the genome, it profoundly slows the evolutionary process (if you have multiple selection pressures). It also shows what happens to the rate of evolution as you increase population, it only marginally accelerates the evolutionary process. So what does it explain, it gives a mathematical basis to explain the evolutionary process seen with HIV, HBV, HCV, TB, Malaria, cancer, weeds,… Oh, it does do one additional thing; it shows that mutation and selection can not evolve a reptile to a bird. You have no selection conditions to accomplish this task and you have far to many genes to transform when mutation and selection is only efficient with single selection conditions, especially for slowly reproducing species like reptiles.
And to answer your comment about helicase and replicase, consider this : what you are doing is applying an ID/creationist belief to the theory of evolution. That belief is purpose (as in "what was the purpose of helicase before it was integrated in the DNA replicating system ?"). You seem to have the same problem with Taffer's statement about believing evolution being about developping a particular (predestined, if you prefer) trait. It is not. It's about following the laws of nature to generate complexity. What you are actually telling is that a lake is formed because the water molecules like that particular spot, and want to go there. What we're saying is that the lake formed because there's a depression in the ground allowing the water to pool there. The latter explanation uses only laws of nature (science), the first a water spirit (religion).
This is a very bizarre statement krazy. Not only is it a failure to answer the question of what helicase and replicase were doing before DNA could be replicated, it completely abandons scientific principles. Science examines and attempts to explain cause and affect processes. You have now degraded the theory of evolution to there is no purpose, it just happens. Your ridiculous attempt at an analogy that evolution is like water filling a depression in the ground lacks something, gravity.
I remember having the exact same discussion with my two creationist friends, whom were considerably more civil than you are. When I pointed this out to them, they could only answer me back, "but don't you need humans (and by extension, your life) to have a purpose ?"
I’m still waiting to have a discussion with an evolutionarian who is not a whining crybaby. Now that you have made a contorted attempt to respond to what helicase and gyrase were doing before DNA could be replicated, why don’t you give us an example of multiple selection pressures accelerating evolution? Oh, that’s right, you have modified the theory of evolution, it is now the theory of evolution by mutation and hole in the ground filling with water (without gravity).
What's your point? I've shown this thread to some of them, and they see nothing wrong with the context of the original posting.
You’ve shown them this and they see nothing wrong with it?
Envision a system of millions of forming and destructive chemical reactions. Now, envision that intermediates of there reactions associate through non-covalent means and that this complex becomes protected against the destructive reactive pathway, perhaps by a reversible precipitation. These new complexes result in a localized increased of new chemical species. These chemical species then progress in a new series of reaction... that is what I mean through cooperative means. I acknowledge this is complete speculation, but well within the range of chemical possibility. As long as there was enough free energy for these reaction to occur.
http://forums.randi.org/images/smilies/doglaugh.gif
Joobz, you have already admitted that you have no idea how ribose could form nonenzymatically and even if you could, I’ve already shown you that it is an unstable molecule with a short half life. You can’t even explain how one of the simplest yet most ubiquitous molecules in life could form spontaneously. Then you go on to speculate that all life can form this way. This is the foundation for the theory of evolution and abiogenesis, irrational speculation, baseless extrapolation, denial of empirical facts and ignorance of mathematics.

Now joobz, is there enough free energy to turn lead into gold?
Paul, you understand how your model works better than this. When your weight matrix finds a match to within the threshold you have located a binding site. When you set the two spurious binding conditions to zero, sequences of bases will evolve at their proper locations that match the weight matrix within the threshold limit. You are trying to squirm out of what your model shows because this was not your original intention.And every other position will also bind to the gene. Do you agree that this is not the same function as the one that evolves when all three pressures are active?
Setting the spurious binding site selection conditions to zero does not mean that every locus in the genome represents a binding site. You may or may not have binding sites at these positions. These sequences will remain random when you don’t impose a selection condition on these portions of the genome. Only the binding site locations will evolve to match the weight matrix. Any other binding site outside the binding site region would be coincidental.
Dr Schneider defined a mathematically explicit selection condition with his weight matrix. Spurious binding occurs when a sequence of bases is matched by the weight matrix where a binding site should not occur. It doesn’t matter whether the spurious binding condition is applied as an individual selection condition or in combination with the other selection conditions.Yes it does. A match can only be "spurious" if there are other matches that are not spurious. If there is only one pressure being applied, then there are no spurious bindings. There are simply bindings or no bindings. The point of this semantic argument is that the same function is not evolving when only one pressure is being applied.
But these “spurious” sites only affect the population when you impose the selection condition. Then “spurious” sites affect the fitness of the population. You need to remember something here Paul. Ev is an idealized model of random point mutation and natural selection. Are you going to try an argue that the sequences that ev is evolving represents codons which will actually transcribe to real proteins which will in turn bind to these binding sites? What ev captures is the essential mathematical behavior of the mutation and selection process, not the evolution of binding sites. Ev simple evolves sequences of bases that satisfy the selection conditions. Ev is sorting the mutations such that beneficial mutations get passed on to future generations according to the selection conditions defined.
The three simultaneous selection conditions evolve sequence of bases which find matches to the weight matrix where binding sites are expected to be found and different sequences of bases that don’t match the weight matrix where binding sites are not expected to be found. If you did your coding properly (and I think you did), your model will eliminate spurious binding when all three selection conditions are applied (and the genome is short enough to allow the model to converge).Correct. And it will not do so when only one selection condition is applied.
You and krazyKemist need to get together and get your story straight. He says there is no purpose to evolution and you are saying that evolution must evolve a particular function. I contend that evolution is the response to selective pressures such that variations which improve the fitness of the population to reproduce are passed along to the next generation. When you run the ev model with the three selection conditions applied, this process becomes profoundly slow on realistic length genomes. When you apply only a single selection pressure in the model, the population can adapt far more rapidly than it can to all three selection conditions simultaneously. Strange as it may seem to you Paul, that is what the empirical evidence shows as well.
Paul, I think that the weight matrix can always find sequence of bases that give matches no matter how large or small the width of the binding site is and no matter how long or short the genome is. It is only when you try to eliminate spurious binding and evolve the binding sites simultaneously that the model has trouble converging.This is because Rcapacity only matters when you're applying all three pressures. Otherwise you are not distinguishing binding sites from other positions.
Paul, you continue to miss the most important point that your model shows, that is three selection conditions evolve far more slowly than single selection conditions. However, let’s say for discussion that your Rcapacity concept has validity. How would you extend this concept to the mutation and selection process seen with viruses and bacteria? I have already shown and will continue to show how multiple selection conditions slow the evolution of these creatures (and other situations as well).
Now Paul, you can ask the following question. Do errors (spurious binding) in the non-binding region have any relationship to reality?Yes, they do. The entire mechanism of gene expression control depends on it.
Well then, you should be able to demonstrate empirical examples of this. We already have huge volumes of empirical evidence of how mutation and selection actually works and it is not evolving binding sites. What ev is demonstrating is that particular sequences of bases can evolve at particular positions of the genome and this process becomes profoundly slow when you have multiple selection conditions evolving simultaneously on realistic length genomes. This effect is seen over and over in the empirical evidence, two more citations are posted below.
Am I the only one who thinks that Klein is spamming, here ?
Belz, you think I am spamming? Actually I think the theory of evolution is a bunch of boloney.
Earlier I suggested he was being deliberately annoying to the extent of troll behavior.
However, Paul assures us of Dr. K's total sincerity.
I still check in on it with a morbid fascination.
Apathia, I only annoy evolutionarians with mathematical and empirical facts. You evolutionarians are very morbid, are you interested in watching the decomposition of the theory of evolution? Let’s show you with some more mathematical and empirical facts of how mutation and selection actually works.

Since you evolutionarians are so slow to understand how mutation and selection actually works, I’ll explain it to you again. Mutation and selection is a sorting process of beneficial and detrimental mutation. As with all sorting processes, this process becomes slower if you increase the number of selection (sorting) conditions. Ev is an elegant demonstration of this effect. This type of mathematical behavior is seen in numerous areas of science including systems optimization, database sorting and iterative problem solving. This effect is nicely explained in Delphi’s Wikipedia reference to the fitness landscape. Evolution by mutation and selection becomes a profoundly slow process when you have multiple selection (sorting) conditions. Only creatures such as viruses and bacteria with huge populations, extremely high reproductive and mutation rates can achieve sufficient number of reproductive cycles to overcome three simultaneous selective pressures and this can take years despite their evolutionary advantages. These mathematical and empirical facts show why it is impossible for reptiles to evolve to birds. There are no selection conditions to do this and there are far too many genes which need to be transformed in order to accomplish this metamorphosis in the small number of generations and small populations available to these life forms in which to accomplish such a task.

So, how does mutation and selection actually work? Here are a couple of more examples which show.

http://jac.oxfordjournals.org/cgi/content/full/52/1/11 (http://jac.oxfordjournals.org/cgi/content/full/52/1/11)

The mutant selection window is an antimicrobial concentration range extending from the minimal concentration required to block the growth of wild-type bacteria up to that required to inhibit the growth of the least susceptible, single-step mutant. The upper boundary is also called the mutant prevention concentration (MPC). Placing antimicrobial concentrations inside the window is expected to enrich resistant mutant subpopulations selectively, whereas placing concentrations above the window is expected to restrict selective enrichment. Since window dimensions are characteristic of each pathogen–antimicrobial combination, they can be linked with antimicrobial pharmacokinetics to rank compounds and dosing regimens in terms of their propensity to enrich mutant fractions of bacterial populations. For situations in which antimicrobial concentrations cannot be kept above the window, restricting the enrichment of mutants requires combination therapy.
And
Consideration of the mutant selection window leads to the suggestion that antimicrobial concentrations between MIC(99) and MPC enrich mutant subpopulations selectively (standard MIC is often quantitatively similar to MIC(99)). Such conditions may suppress most infections,39,60 especially when host defences effectively eliminate pathogens. However, when large numbers of patients are treated at concentrations inside the selection window, susceptibility decreases gradually. Eventually a point is reached at which the antimicrobial agent becomes ineffective. According to these ideas, restricting the development of resistance requires that antimicrobial concentrations at the site of infection be kept above MPC. If that cannot be done for a given agent–pathogen combination, the agent should be used as part of a combination therapy involving agents with different targets. Such an approach is likely to be required for plasmid-borne resistance.

The effects of lethal action have not been integrated into the mutant selection window hypothesis, although they are certainly important to the development of resistance. The most obvious effect is the reduction in bacterial load. This facilitates host defence-mediated removal of bacteria and reduces the probability that new mutants will arise. However, an agent that kills susceptible cells but not mutants will enrich pre-existing mutants. Thus desirable agents should also kill resistant mutants.24,61–63 For such compounds, therapeutic drug concentrations may not need to be kept above MPC throughout therapy to restrict mutant enrichment.

Whether exceeding the MPC is sufficient to restrict the development of resistance requires clinical testing. Such tests are important because numerical considerations, such as mutation frequencies and relevant drug concentrations, could depend significantly on whether the microbes are growing on agar plates or in host organisms. Moreover, fluctuations in antimicrobial pharmacokinetics could require dosing adjustments to make MPC an effective threshold. Animal and clinical studies now seem justified, since a mutant selection window can be measured for many pathogen–antimicrobial combinations.64

http://www.anopheles.org/showabstract.php?pmid=10697872 (http://www.anopheles.org/showabstract.php?pmid=10697872)
Resistance to antimalarial drugs arises when spontaneously occurring mutants with gene mutations or amplifications which confer reduced drug susceptibility are selected, and are then transmitted. Simultaneous use of two or more antimalarials with different modes of action and which therefore do not share the same resistance mechanisms will reduce the chance of selection, because the chance of a resistant mutant surviving is the product of the parasite mutation rates for the individual drugs, multiplied by the number of parasites in an infection that are exposed to the drugs. The artemisinin derivatives are very active antimalarials, which produce large reductions in parasite biomass per asexual cycle, and reduce malaria transmissibility. To date no resistance to these drugs has been reported. These drugs therefore make particularly effective combination partners. This suggests that antimalarial drugs should not be used alone in treatment, but always in combination, as in the treatment of tuberculosis or HIV, and that the combination should include artemisinin or one of its derivatives.
Simultaneous selection pressures slow evolution, which is how mutation and selection works.

[Belz...]

Simultaneous selection pressures slow evolution, which is how mutation and selection works.

That's starting to be very circular.

So you mathematically challenged evolutionarians are still having difficulty shedding light on the mathematics of mutation and selection.

2+2 = 4.

There. I've just posted more mathematical proof of anything than you ever did.

[Dr Adequate]

Let’s repeat for everyone what Taffer said.

Adequate, we all know what a twisted convoluted mind you have, after all here is how you think mutation and selection works.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

So are you talking about evolution or emergence silly evolutionarian? Give us an example of multiple selection pressures accelerating either emergence of resistance or evolution. You can’t because your graph is nonsense and mutation and selection does not work the way you allege. Whether you want to call it emergence of resistance or evolution, mutation and selection slows profoundly when you have multiple selection pressures.

Paul, you understand how your model works better than this. When your weight matrix finds a match to within the threshold you have located a binding site. When you set the two spurious binding conditions to zero, sequences of bases will evolve at their proper locations that match the weight matrix within the threshold limit. You are trying to squirm out of what your model shows because this was not your original intention. What your model in fact shows is how multiple selection conditions affects evolution by mutation and selection. It just so happens that this fits the empirical data (I have another example posted below) very nicely. It also fits Delphi’s reference to fitness landscape in Wikipedia. Your program shows exactly how the mutation selection process works but you have gone into denial because it does not fit your belief system.

Dr Schneider defined a mathematically explicit selection condition with his weight matrix. Spurious binding occurs when a sequence of bases is matched by the weight matrix where a binding site should not occur. It doesn’t matter whether the spurious binding condition is applied as an individual selection condition or in combination with the other selection conditions. A match is counted as a mistake when the weight matrix finds a match where it should not occur (when that selection condition is nonzero). The three simultaneous selection conditions evolve sequence of bases which find matches to the weight matrix where binding sites are expected to be found and different sequences of bases that don’t match the weight matrix where binding sites are not expected to be found. If you did your coding properly (and I think you did), your model will eliminate spurious binding when all three selection conditions are applied (and the genome is short enough to allow the model to converge).

Paul, I think that the weight matrix can always find sequence of bases that give matches no matter how large or small the width of the binding site is and no matter how long or short the genome is. It is only when you try to eliminate spurious binding and evolve the binding sites simultaneously that the model has trouble converging. The simultaneous selection conditions confound the selection process. As you lengthen the genome in the model, you lengthen the non-binding site region of the genome. It is mistakes in this region which ultimately slow and then stop the convergence of your model. Large binding site widths give you a little reprieve from this effect because it keeps down the number of mistakes in the non-binding site region but ultimately, as you lengthen the genome (and the non-binding site region), errors in this region slow and then stop convergence of the model.

Now Paul, you can ask the following question. Do errors (spurious binding) in the non-binding region have any relationship to reality? While you are pondering this, ponder the following citation as well.

http://www.natap.org/2006/ResisWksp/ResisWksp_02.htm (http://www.natap.org/2006/ResisWksp/ResisWksp_02.htm)

and

There is so much evidence how mutation and selection actually works, I find it amazing that evolutionarians have so little understanding of this process. Multiple selection pressures slow evolution. That is what the mathematics of ev shows, that is what Delphi’s Wikipedia reference to the fitness landscape shows and that is what the massive amount of empirical evidence of mutation and selection shows.

So you mathematically challenged evolutionarians are still having difficulty shedding light on the mathematics of mutation and selection. Since you are having this difficulty understanding what ev shows mathematically, that is multiple selection pressures profoundly slow the evolutionary process, I will post more empirical examples which show this. But first, your interrogatories.

If that is the case lita’ gator; when are you going to so graciously accept the mathematical and empirical fact that multiple selection pressures accelerate evolution? The evidence is overwhelming; I’ll post a couple more citations below.

Now listen krazy, I have to address my comments to the intellectual level of the audience. So let’s consider the Pseudomonas efflux pump. This pump has the capability to pump out a variety of chemically unique and unrelated toxins. Why don’t the Pseudomonas bacteria maintain this pump all the time in its population? Do you think that humans subjecting these bacteria to antibiotics are the first time Pseudomonas ever was subjected to a toxin?

Oh, ev doesn’t explain everything about evolution, but it does explain something about the mathematics of mutation and selection. The things that it does show is what happens when you have multiple selection pressures, profoundly slows the evolutionary process. It also shows what happens to the rate of evolution as you lengthen the genome, it profoundly slows the evolutionary process (if you have multiple selection pressures). It also shows what happens to the rate of evolution as you increase population, it only marginally accelerates the evolutionary process. So what does it explain, it gives a mathematical basis to explain the evolutionary process seen with HIV, HBV, HCV, TB, Malaria, cancer, weeds,… Oh, it does do one additional thing; it shows that mutation and selection can not evolve a reptile to a bird. You have no selection conditions to accomplish this task and you have far to many genes to transform when mutation and selection is only efficient with single selection conditions, especially for slowly reproducing species like reptiles.

This is a very bizarre statement krazy. Not only is it a failure to answer the question of what helicase and replicase were doing before DNA could be replicated, it completely abandons scientific principles. Science examines and attempts to explain cause and affect processes. You have now degraded the theory of evolution to there is no purpose, it just happens. Your ridiculous attempt at an analogy that evolution is like water filling a depression in the ground lacks something, gravity.

I’m still waiting to have a discussion with an evolutionarian who is not a whining crybaby. Now that you have made a contorted attempt to respond to what helicase and gyrase were doing before DNA could be replicated, why don’t you give us an example of multiple selection pressures accelerating evolution? Oh, that’s right, you have modified the theory of evolution, it is now the theory of evolution by mutation and hole in the ground filling with water (without gravity).

You’ve shown them this and they see nothing wrong with it?
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http://forums.randi.org/images/smilies/doglaugh.gif
Joobz, you have already admitted that you have no idea how ribose could form nonenzymatically and even if you could, I’ve already shown you that it is an unstable molecule with a short half life. You can’t even explain how one of the simplest yet most ubiquitous molecules in life could form spontaneously. Then you go on to speculate that all life can form this way. This is the foundation for the theory of evolution and abiogenesis, irrational speculation, baseless extrapolation, denial of empirical facts and ignorance of mathematics.

Now joobz, is there enough free energy to turn lead into gold?

Setting the spurious binding site selection conditions to zero does not mean that every locus in the genome represents a binding site. You may or may not have binding sites at these positions. These sequences will remain random when you don’t impose a selection condition on these portions of the genome. Only the binding site locations will evolve to match the weight matrix. Any other binding site outside the binding site region would be coincidental.

But these “spurious” sites only affect the population when you impose the selection condition. Then “spurious” sites affect the fitness of the population. You need to remember something here Paul. Ev is an idealized model of random point mutation and natural selection. Are you going to try an argue that the sequences that ev is evolving represents codons which will actually transcribe to real proteins which will in turn bind to these binding sites? What ev captures is the essential mathematical behavior of the mutation and selection process, not the evolution of binding sites. Ev simple evolves sequences of bases that satisfy the selection conditions. Ev is sorting the mutations such that beneficial mutations get passed on to future generations according to the selection conditions defined.

You and krazyKemist need to get together and get your story straight. He says there is no purpose to evolution and you are saying that evolution must evolve a particular function. I contend that evolution is the response to selective pressures such that variations which improve the fitness of the population to reproduce are passed along to the next generation. When you run the ev model with the three selection conditions applied, this process becomes profoundly slow on realistic length genomes. When you apply only a single selection pressure in the model, the population can adapt far more rapidly than it can to all three selection conditions simultaneously. Strange as it may seem to you Paul, that is what the empirical evidence shows as well.

Paul, you continue to miss the most important point that your model shows, that is three selection conditions evolve far more slowly than single selection conditions. However, let’s say for discussion that your Rcapacity concept has validity. How would you extend this concept to the mutation and selection process seen with viruses and bacteria? I have already shown and will continue to show how multiple selection conditions slow the evolution of these creatures (and other situations as well).

Well then, you should be able to demonstrate empirical examples of this. We already have huge volumes of empirical evidence of how mutation and selection actually works and it is not evolving binding sites. What ev is demonstrating is that particular sequences of bases can evolve at particular positions of the genome and this process becomes profoundly slow when you have multiple selection conditions evolving simultaneously on realistic length genomes. This effect is seen over and over in the empirical evidence, two more citations are posted below.

Belz, you think I am spamming? Actually I think the theory of evolution is a bunch of boloney.

Apathia, I only annoy evolutionarians with mathematical and empirical facts. You evolutionarians are very morbid, are you interested in watching the decomposition of the theory of evolution? Let’s show you with some more mathematical and empirical facts of how mutation and selection actually works.

Since you evolutionarians are so slow to understand how mutation and selection actually works, I’ll explain it to you again. Mutation and selection is a sorting process of beneficial and detrimental mutation. As with all sorting processes, this process becomes slower if you increase the number of selection (sorting) conditions. Ev is an elegant demonstration of this effect. This type of mathematical behavior is seen in numerous areas of science including systems optimization, database sorting and iterative problem solving. This effect is nicely explained in Delphi’s Wikipedia reference to the fitness landscape. Evolution by mutation and selection becomes a profoundly slow process when you have multiple selection (sorting) conditions. Only creatures such as viruses and bacteria with huge populations, extremely high reproductive and mutation rates can achieve sufficient number of reproductive cycles to overcome three simultaneous selective pressures and this can take years despite their evolutionary advantages. These mathematical and empirical facts show why it is impossible for reptiles to evolve to birds. There are no selection conditions to do this and there are far too many genes which need to be transformed in order to accomplish this metamorphosis in the small number of generations and small populations available to these life forms in which to accomplish such a task.

So, how does mutation and selection actually work? Here are a couple of more examples which show.

http://jac.oxfordjournals.org/cgi/content/full/52/1/11 (http://jac.oxfordjournals.org/cgi/content/full/52/1/11)

And


http://www.anopheles.org/showabstract.php?pmid=10697872 (http://www.anopheles.org/showabstract.php?pmid=10697872)

Simultaneous selection pressures slow evolution, which is how mutation and selection works. So, you still haven't done any mathematics, found any evidence, found a counterexample to my model, or offered a critique of my model more profound than a little cartoon of a little dog. And you still have no idea how multiple drug therapy works. However, the following is undoubtedly a new lie:

Oh, that’s right, you have modified the theory of evolution, it is now the theory of evolution by mutation and hole in the ground filling with water (without gravity). It's a very stupid lie, isn't it? --- 'cos we can all see that you're lying. Still, at least that's one part of your gibberish that you didn't have computer-generated for you.

[joobz]

Joobz, you have already admitted that you have no idea how ribose could form nonenzymatically and even if you could, I’ve already shown you that it is an unstable molecule with a short half life. You can’t even explain how one of the simplest yet most ubiquitous molecules in life could form spontaneously. Then you go on to speculate that all life can form this way. This is the foundation for the theory of evolution and abiogenesis, irrational speculation, baseless extrapolation, denial of empirical facts and ignorance of mathematics.

Now joobz, is there enough free energy to turn lead into gold?
Ah, so you wish to misquote to distract for your mistakes.

No one is fooled.

[Dr Adequate]

Oh, and you still haven't answered this question.

Let's see if we can explain it in language that kleinman would understand. Suppose a stupid lunatic thinks he hears a magic sky fairy telling him to gather two of every kind of animal.

Because he's a halfwit, he goes wandering around at random looking for the animals.

Now, consider the following two options:

(1) He collects the animals he stumbles across in strict alphabetical order, starting with aardvarks and working his way along the list. If he happens to see an animal, and it's not the next one on his list, he ignores it.

(2) When he sees an animal, if he hasn't already got a pair, he collects it.

Which method do you think would be faster?

NOTE FOR COMPLETE MORONS, I.E. KLEINMAN: the fact that both methods take longer the more animals there are on the list does not somehow magically mean that the first method is better. Which is faster?

[kleinman]

Simultaneous selection pressures slow evolution, which is how mutation and selection works.That's starting to be very circular.
Mutation and selection has always been circular, it is a cycle and a very slow acting cycle at that.
So you mathematically challenged evolutionarians are still having difficulty shedding light on the mathematics of mutation and selection.2+2 = 4.

There. I've just posted more mathematical proof of anything than you ever did.
Read the entire thread and you will find the mathematical proof. If you are too lazy to do that, I’ll repost the data from ev that shows how mutation and selection works. Of course that would be very circular.
So, you still haven't done any maths, found any evidence, found a counterexample to my model, or offered a critique of my model more profound than a little cartoon of a little dog. However, the following is undoubtedly a new lie:
Your model, do you mean the silly graph you posted:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
We are still waiting for you to post your first example which shows that multiple selection pressures accelerate evolution. I have already posted more than 100 counter examples which show that multiple selection pressures slow evolution. Here, have another one mathematically challenged evolutionarian.

http://www.annals.org/cgi/content/full/128/11/951 (http://www.annals.org/cgi/content/full/128/11/951)
For anti-HIV drugs to have long-term benefits, however, they must be used in a way that will completely suppress viral replication. This is because HIV, like any other microorganism, develops resistance to even the most potent suppressive agents if it is allowed to replicate, even slowly, in the presence of those agents. Drug resistance evolves through the accumulation of replication errors (mutations) in the viral population and the preferential survival of the mutants best able to replicate in the presence of the drug. This replication sets the stage for new rounds of mutation and selection, increasing the level of drug resistance over time. Thus, the evolution of drug resistance is a strict Darwinian process, driven by viral replication, mutation, and selection [7, 8].

Because mutations arise as replication errors, they are a direct result of the viral replication process itself. The probability that any new mutation will occur is thus a direct function of the extent of ongoing viral replication. Potent inhibition of viral replication with therapy can greatly suppress the emergence of resistance in a nonspecific manner [9]. Indeed, if a regimen is potent enough to block all viral replication, it should be possible, in theory, to prevent the emergence of resistance altogether.

But simply having drugs with great antiviral potency is not enough. This is because, for many drugs, mutations engendering moderate- to high-level resistance are likely to exist, even before therapy. It has been estimated that because of the high viral mutation rate, rapid viral turnover, and high viral load in HIV-infected persons, every possible single nucleotide substitution mutation occurs 104 to 105 times per day in a given patient [7]. Thus, most, if not all, single amino acid substitution mutations are likely to preexist. If any of these mutations confers a significant degree of resistance to the drug or drugs used, the virus will be allowed to replicate and to evolve greater resistance. Under these circumstances, even a very potent regimen may be inadequate to contain the viral population for an extended period. This is true of all known non-nucleoside reverse transcriptase inhibitors and also of many protease inhibitors and nucleoside reverse transcriptase inhibitors.

Long-term viral suppression, therefore, requires that a high genetic barrier to resistance be established. Simply put, the regimen should require the viral population to acquire as many new mutations as possible before the level of resistance becomes high enough to overcome the block imposed by therapy [8]. This can be accomplished in several ways.

First, using drugs that require the virus to undergo multiple mutations to achieve high-level resistance maximizes the efficacy of the drug for the existing viral population and minimizes the probability of breakthrough. In this respect, a drug to which resistance develops after only a single amino acid substitution is expected to be more vulnerable to resistance than an equipotent drug that requires the virus to undergo multiple mutations to achieve the same degree of resistance.

Second, the need for multiple mutations can be increased further by combining different drugs that inhibit independent targets. Three distinct therapeutic classes of drugs with nonoverlapping sets of resistance determinants exist: protease inhibitors, nucleoside inhibitors, and non-nucleoside reverse transcriptase inhibitors. There is no evidence that mutations compromising the effects of members of one class will reduce the utility of members of any other class. This is one of the most important benefits of divergent combination therapy: When many simultaneous mutations are required, the probability of preexisting resistance in a therapy-naive patient becomes negligible and the effect of the drug combination is maximized.
See Adequate, this is how mutation and selection works. It does not work like you try to allege with your silly graph, if it did, combination therapy for HIV would accelerate the resistance of the virus, but it doesn’t. Now, if you could post a citation of a single real example that behaves like your silly graph, you could make this an interesting discussion, but you can’t, So what’s the score, 100+ counterexamples to 0 examples of your silly graph. I almost feel sorry for you with your taking up this ridiculous position but on the other hand, I do so enjoy annoying you with these mathematical and empirical facts of how mutation and selection actually works.

[Belz...]

Belz, you think I am spamming?

Because you keep quoting the same paragraphs, posting the same graphs and saying the same stuff over and over again without actually debating.

You're just preaching.

Actually I think the theory of evolution is a bunch of boloney.

I know that's what you think, but it's not what you're proving.

Simultaneous selection pressures slow evolution, which is how mutation and selection works.
That's starting to be very circular.

Mutation and selection has always been circular, it is a cycle and a very slow acting cycle at that.

You're either not very smart or you're acting like you don't understand my posts. YOU'RE being circular.

Read the entire thread and you will find the mathematical proof.

Saying that a computer model does not support evolution does not mean you have mathematical proof.

[kjkent1]

If that is the case lita’ gator; when are you going to so graciously accept the mathematical and empirical fact that multiple selection pressures accelerate evolution?Just as soon as you affirmatively prove your case. So far, the evidence of evolution is undeniable, and the only thing you've proven is that point mutation and selection for spurious and missing bindings is too slow, by itself, to evolve the entire landscape of living organisms.

Until you prove that the addition of all of the other mutational and selection mechanisms cannot accomplish the current outcome of life, you haven't made your case -- which admittedly, is a nearly impossible feat. Proving a negative is a task fit only for Don Quixote. Mere mortals must build their cases on affirmative proofs.

And, as you are apparently unwilling to do the work necessary to build an affirmative case, you will be forever viewed as only the "annoying creationist," instead of the "respected scientist."

[kleinman]

Belz, you think I am spamming?Because you keep quoting the same paragraphs, posting the same graphs and saying the same stuff over and over again without actually debating.
I think you are confusing me with Adequate. He’s the one who takes my posts, reposts them and whines one or two lines that I am lying. I have posted over 100 different citations which show how mutation and selection works and it works just like Dr Schneider’s peer reviewed a published computer simulation of mutation and selection works. What that model shows and what the empirical evidence shows is that multiple selection pressures profoundly slow the evolutionary process. Adequate has posted a graph where he contends that multiple selection pressures accelerate evolution. He has yet to post a single example of this. The reason he can’t post an example of this is his graph is a fake. The contrast between our two views could not be starker. I have a peer reviewed and published model of mutation and selection which supports my view point and I have posted over 100 examples of this while Adequate has his own silly graph and no real examples of his viewpoint. So prepare yourself to see Adequate’s graph over and over until he either posts a citation which demonstrates his allegation or he admits his graph is a fake.
Actually I think the theory of evolution is a bunch of boloney.I know that's what you think, but it's not what you're proving.
All you have to do Belz is go into denial about what the mathematics of mutation and selection shows and the corresponding empirical evidence that demonstrates this mathematics and nothing will be proved to you evolutionarians.

[Taffer]

Wow, what a powerful argument. Emergence of a particular trait by mutation and selection is not evolution. So now we have the theory of evolution by mutation and selection and we have the theory of emergence by mutation and selection.

As always, you argue against a strawman of my post rather then the actual thing. Lets carefully look at what I said, shall we?

Evolution is, by definition, the change in allele frequencies in a population over time. This is a rate of change. You are arguing that increasing selection pressure reduces this rate of change.

The article you site, however, talks about the emergence of a particular trait. The nomenclature, in this case, can lead to some confusion, as often in the field a phrase like "trait X evolved" is used, equating evolution with emergence. However, the underlying principle of emergence of a specific trait is different to the rate of evolution. I shall explain below:

Lets start of by considering what effects the rate of change of allele frequency (hereafter evolutionary rate). Let us consider a single locus on a genome of which there exists two alleles. For the sake of argument, let us also assume that the allele is newly arisen, and encodes a dominant trait leading to some antibacterial resistance. Let us further assume that the bacteria in question are being grown in a medium containing said antibacterial.

Given the above, the dominant allele will have some evolutionary benefit. Thus, the more common, recessive allele will be selected against. This is because, although it is far more common then the newly arisen allele, it no longer has the highest fitness. In a situation such as this, the frequency of the dominant allele is given by p, and the frequency of the recessive allele is given by q. Assuming that the population is in Hardy-Weinberg Equilibrium, the frequency distributions of different individual genotypes in the population will be given by (p^2)*2pq*(q^2)=1. In other words, the frequency of homozygous dominant individuals is given by P^2, the frequency of heterozygous individuals is given by 2pq, and the frequency of homozygous recessive individuals is given by q^2.

Now, we will look at the change in allele frequency over time - evolution. Because we are considering a situation wherein the recessive allele is less fit then the dominant allele, we can ascribe some selection coefficient to the homozygous recessive genotype, denoted by s. Thus, because the most-fit allele is dominant, the fitnesses of homozygous dominant and heterozygous individuals is 1, while the fitness of homozygous recessive individuals is less then 1, 1-s. Now we come to the crux of the matter. The change in allele frequency of the recessive allele, Δq, is given by the equation Δq=(-spq^2)/(1-(q^2)s). This number will be less then 0, because the frequency is lower after each generation (it is being selected against). Now, look carefully at the equation. If we increase the level of selection against q, i.e. increase s, we see that the recessive allele becomes even less fit, as we would expect. Furthermore, increasing s in the equation above means that the numerator increases, while the denominator decreases. This has the effect of making Δq a larger negative number. What does this mean? Increase the selection pressures, and the frequency of the less-fit allele will change faster over time. What is a change in allele frequency over time? Evolution!

Now, however, we must look at what you are talking about. You give a citation which states, to paraphrase, that increased numbers of antibacterials mean it takes longer for resistance of all three antibacterials to arise in the population. You use this to argue that evolution cannot happen. However, as we have already seen above, evolution happens faster when we have more selection. So, what is the paper (and every paper you have cited that I have looked at) actually saying?

It is saying that it takes longer for a particular trait (antibacterial resistance) to emerge. The difference between emergence and evolution is that, when we are talking about a particular trait emerging, we are talking about a trait which does not already exist in the population. For evolution to occur, there must be existing variation in a population. If you have a population of bacteria within which does not exist individuals with all the traits you are looking for in the starting population, then selection will not drive the frequency of those traits until they do exist. What causes variation in a population? Well, many things, but you are focusing on mutation. You claim that increased selection pressures slow the rate of evolution. However, if an allele does not exist in a population, then what effects the time until it arises is not the rate of change of alleles in a population (evolution, remember), but the rate of mutation in the population (and any other sources of variation, but I will only focus on mutation). Mutation, however, is in no way effected by selection pressures. Thus, it makes no sense to assume that the rate of mutation is affected by the level of selection in a population.

You also make the claim that it will take longer to evolve 3 traits in parallel then in series. But think about how mutation occurs. The mutation rate at one locus can be given by μ. So, if 3 mutation events are to occur in series, we would expect a frequency of μ*μ*μ, or μ^3. If they are to occur in parallel, we would expect the same frequency. Why? Because each mutation event is independant of the other. Thus, just as many mutation events are happening, whether it is in parallel or series. Thus, it makes not difference to the "time it takes for 3 antibacterials to evolve" whether they appear one after another, or whether they appear all at once.

Then what are the papers saying? They are saying that the rate at which resistance emerges (i.e. a mutation event so it exists in a population, and then selection so it exists in a significant level- which will happen quickly) is lower when you use multiple antibacterials then when you use only one. It should be clear, by now, that this would be the case. Why? Because evolving 3 antibacterial resistance alleles will take longer then evolving only 1. Couple this with the fact that multiple antibacterial agents tend to reduce the population of bacteria more then using only a single agent, and other factors, and it should be clear that the chance a new mutation will arise in the population is much lower.

However, please understand that the rate of evolution is increased when higher (i.e. multiple) selection exists, and that this fact is unrelated to the fact that antibacterial agents make the emergence of a resistance trait to all agents more unlikely then using only a single agent.

[Belz...]

I have posted over 100 different citations which show how mutation and selection works and it works just like Dr Schneider’s peer reviewed a published computer simulation of mutation and selection works.

All you have to do Belz is go into denial about what the mathematics of mutation and selection shows and the corresponding empirical evidence that demonstrates this mathematics and nothing will be proved to you evolutionarians.

This coming from someone who consistently ignores other people who prove him wrong.

No, I think I'll just wait until you show actual proof that a) you understand what you're talking about and b) that your views correspond with reality.

[kleinman]

Wow, what a powerful argument. Emergence of a particular trait by mutation and selection is not evolution. So now we have the theory of evolution by mutation and selection and we have the theory of emergence by mutation and selection.As always, you argue against a strawman of my post rather then the actual thing. Lets carefully look at what I said, shall we?
Only in your dreams in this argument a strawman as you try to say emergence of drug resistance is not evolution. So let’s take a closer look at your arguments.
Evolution is, by definition, the change in allele frequencies in a population over time. This is a rate of change. You are arguing that increasing selection pressure reduces this rate of change.
Stabilizing selection pressures reduce the diversity in the population, these types of selection pressures favor the portion of the population that is at the local optimum on the fitness landscape and removes the phenodeviants from the population. Stabilizing selection pressure can and do cause the loss of alleles. Directional selection pressures select for the portion of the population that is most fit to that pressure. If the population is subjected to more than a single selection pressure, it confounds the populations’ ability to adapt to the multiple selection pressures simultaneously by mutation and selection.
The article you site, however, talks about the emergence of a particular trait. The nomenclature, in this case, can lead to some confusion, as often in the field a phrase like "trait X evolved" is used, equating evolution with emergence. However, the underlying principle of emergence of a specific trait is different to the rate of evolution. I shall explain below:
Don’t you mean the over hundred articles I site? Before we go on, let’s see what Wikipedia says about emergence and evolution.
http://en.wikipedia.org/wiki/Evolution (http://en.wikipedia.org/wiki/Evolution)
A species is a group of organisms that can reproduce with one another. However, when a species is separated into populations that are prevented from interbreeding, mutations, genetic drift, and the selection of different traits by different environments cause the accumulation of differences over generations and the emergence of new species.[4]
and
Soon after the emergence of these first multicellular organisms, a remarkable amount of biological diversity appeared over approximately 10 million years, in an event called the Cambrian explosion. Here, the majority of types of modern animals evolved, as well as unique lineages that subsequently became extinct.[143]
Emergence-appearance, coming out, materialization, surfacing. That is what emergence means. All the citations I have posted are examples of evolution by mutation and selection, the resistance emerges by the mechanism of mutation and selection. You are the one confused about the nomenclature. Why don’t you give an example of emergence of a trait is evolution?
Lets start of by considering what effects the rate of change of allele frequency (hereafter evolutionary rate). Let us consider a single locus on a genome of which there exists two alleles. For the sake of argument, let us also assume that the allele is newly arisen, and encodes a dominant trait leading to some antibacterial resistance. Let us further assume that the bacteria in question are being grown in a medium containing said antibacterial.
You evolutionarians love to confuse recombination and selection with mutation and selection but let’s go on.
Given the above, the dominant allele will have some evolutionary benefit. Thus, the more common, recessive allele will be selected against. This is because, although it is far more common then the newly arisen allele, it no longer has the highest fitness. In a situation such as this, the frequency of the dominant allele is given by p, and the frequency of the recessive allele is given by q. Assuming that the population is in Hardy-Weinberg Equilibrium, the frequency distributions of different individual genotypes in the population will be given by (p^2)*2pq*(q^2)=1. In other words, the frequency of homozygous dominant individuals is given by P^2, the frequency of heterozygous individuals is given by 2pq, and the frequency of homozygous recessive individuals is given by q^2.
Taffer, the Hardy-Weinberg law applies to recombination and natural selection. In fact, if you have no selection pressures on a population which recombines randomly, you can not change the frequency of alleles in the population. What you still don’t understand is that recombination without error can not increase the information in the gene pool and recombination with natural selection can and does cause the loss of alleles (information) from the gene pool. Now there are factors which can alter the Hardy-Weinberg equilibrium such as mutations, nonrandom mating and selection pressures. It requires computations like that done by Dr Schneider in order to compute how mutations and selection will increase information in the gene pool. The Hardy-Weinberg law does not address this. You have started this point talking about antibacterial resistance (bacteria reproduce by cell division and have only a single chromosome) and merged this with a discussion with recombination which occurs by meiosis and require multiple chromosomes for the exchange of information. You are confused about the mechanisms of genetic change. If you think you are correct, give us a real example of multiple selection pressures (with or without recombination) which accelerate evolution. I have already posted several examples of life forms that reproduce by recombination, the evolution of which is slowed by multiple selection pressures. If you have trouble finding one, look at what happens with the Malaria parasite despite its ability to do recombination when combination selection pressures are applied. This is the real evidence of how mutation and selection actually works and recombination does not overcome this mathematical and empirical fact that multiple selection pressures profoundly slow the ability of a population to evolve, with or without recombination.

Here’s another empirical example of how mutation and selection works, this creature does recombination yet still combination selection pressures slow the ability of this life form to evolve resistance to combination selection pressures.

http://www.biology.ed.ac.uk/research/groups/phunt/profile.php (http://www.biology.ed.ac.uk/research/groups/phunt/profile.php)
Despite the efforts of the scientific community, the world-wide burden of malaria is currently increasing; it now accounts for over 1 million deaths yearly, mostly child mortalities in Africa. Undoubtedly, one major factor has been the catastrophic spread of malaria parasites which are resistant to antimalarial drugs such as chloroquine, pyrimethamine (PYR) and the combination therapy, Fansidar (pyrimethamine + sulfadoxine (S/P)). Presently, artemisinin and its derivatives are increasingly recommended as first-line anti-malarial therapies, particularly in combination with other drugs, such as amodiaquine, piperaquine, mefloquine and S/P. This strategy is used to increase efficacy and to reduce the probability of resistant parasites surviving and spreading.
If you want to stop evolution, use combination selection pressures.

[Dr Adequate]

Mutation and selection has always been circular, it is a cycle and a very slow acting cycle at that.

Read the entire thread and you will find the mathematical proof. If you are too lazy to do that, I’ll repost the data from ev that shows how mutation and selection works. Of course that would be very circular.

Your model, do you mean the silly graph you posted:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

We are still waiting for you to post your first example which shows that multiple selection pressures accelerate evolution. I have already posted more than 100 counter examples which show that multiple selection pressures slow evolution. Here, have another one mathematically challenged evolutionarian.

http://www.annals.org/cgi/content/full/128/11/951 (http://www.annals.org/cgi/content/full/128/11/951)

See Adequate, this is how mutation and selection works. It does not work like you try to allege with your silly graph, if it did, combination therapy for HIV would accelerate the resistance of the virus, but it doesn’t. Now, if you could post a citation of a single real example that behaves like your silly graph, you could make this an interesting discussion, but you can’t, So what’s the score, 100+ counterexamples to 0 examples of your silly graph. I almost feel sorry for you with your taking up this ridiculous position but on the other hand, I do so enjoy annoying you with these mathematical and empirical facts of how mutation and selection actually works. So, you still haven't done any mathematics, found any evidence, found a counterexample to my model, offered a critique of my model, or grasped how multiple drug therapy works.

No new lies, huh?

[Dr Adequate]

I think you are confusing me with Adequate. He’s the one who takes my posts, reposts them and whines one or two lines that I am lying. I have posted over 100 different citations which show how mutation and selection works and it works just like Dr Schneider’s peer reviewed a published computer simulation of mutation and selection works. What that model shows and what the empirical evidence shows is that multiple selection pressures profoundly slow the evolutionary process. Adequate has posted a graph where he contends that multiple selection pressures accelerate evolution. He has yet to post a single example of this. The reason he can’t post an example of this is his graph is a fake. The contrast between our two views could not be starker. I have a peer reviewed and published model of mutation and selection which supports my view point and I have posted over 100 examples of this while Adequate has his own silly graph and no real examples of his viewpoint. So prepare yourself to see Adequate’s graph over and over until he either posts a citation which demonstrates his allegation or he admits his graph is a fake.

All you have to do Belz is go into denial about what the mathematics of mutation and selection shows and the corresponding empirical evidence that demonstrates this mathematics and nothing will be proved to you evolutionarians. If it really upsets you so much to have me point out that you're reciting the same stupid lies over and over, then you could always stop reciting the same stupid lies over and over.

The solution is in your own hands.

Think of some new lies.

[Taffer]

Stabilizing selection pressures reduce the diversity in the population, these types of selection pressures favor the portion of the population that is at the local optimum on the fitness landscape and removes the phenodeviants from the population. Stabilizing selection pressure can and do cause the loss of alleles. Directional selection pressures select for the portion of the population that is most fit to that pressure. If the population is subjected to more than a single selection pressure, it confounds the populations’ ability to adapt to the multiple selection pressures simultaneously by mutation and selection.

Firstly, wrong. Secondly, what does that have to do with what I quoted?

Don’t you mean the over hundred articles I site?

Yes, I do. I can say this with some certainty, because I understand evolutionary theory, and you obviously do not.

Before we go on, let’s see what Wikipedia says about emergence and evolution.[/SIZE][/FONT]
http://en.wikipedia.org/wiki/Evolution (http://en.wikipedia.org/wiki/Evolution)

and


:rolleyes:

A single word can have multiple meanings. In both those cases, the word "emergence" is used to mean something different to how I use it. If you read my post, you will understand what I mean, and why those two quotes are saying something different.

Emergence-appearance, coming out, materialization, surfacing. That is what emergence means. All the citations I have posted are examples of evolution by mutation and selection, the resistance emerges by the mechanism of mutation and selection. You are the one confused about the nomenclature. Why don’t you give an example of emergence of a trait is evolution?

No, I am not confused by the nomenclature. The nomenclature is obscure and often buddled by multiple meanings of the different words in question. I have cleary explained what I mean by "emergence".

You evolutionarians love to confuse recombination and selection with mutation and selection but let’s go on.

For the millionth time, kleinman, there is no difference between the two. Both produce variation, and thus both allow evolution to occur.

Taffer, the Hardy-Weinberg law applies to recombination and natural selection. In fact, if you have no selection pressures on a population which recombines randomly, you can not change the frequency of alleles in the population.

Yes, kleinman, I know that.

What you still don’t understand is that recombination without error can not increase the information in the gene pool

Wrong.

and recombination with natural selection can and does cause the loss of alleles (information) from the gene pool.

It also leads to gain of alleles.

You do realise that recombination is considered a type of mutation, right?

Now there are factors which can alter the Hardy-Weinberg equilibrium such as mutations, nonrandom mating and selection pressures. It requires computations like that done by Dr Schneider in order to compute how mutations and selection will increase information in the gene pool. The Hardy-Weinberg law does not address this.

I never said it did. Read what I said again. I said we started with a population under Hardy-Weinberg.

You have started this point talking about antibacterial resistance (bacteria reproduce by cell division and have only a single chromosome) and merged this with a discussion with recombination which occurs by meiosis and require multiple chromosomes for the exchange of information.

No, I have not. Please state exactly where I mention recombination? I only mention selection. That is because that is all that is important.

You are confused about the mechanisms of genetic change.

No, I am not.

If you think you are correct, give us a real example of multiple selection pressures (with or without recombination) which accelerate evolution.

I have already given you a mathematical proof. What more do you require?

I have already posted several examples of life forms that reproduce by recombination

Organisms do not "reproduce by recombination"

, the evolution of which is slowed by multiple selection pressures.

No, it is not. Recombination produces variation. Mutation produces variation. It doesn't matter how the variation arises, only that it exists.

If you have trouble finding one, look at what happens with the Malaria parasite despite its ability to do recombination when combination selection pressures are applied. This is the real evidence of how mutation and selection actually works and recombination does not overcome this mathematical and empirical fact that multiple selection pressures profoundly slow the ability of a population to evolve, with or without recombination.[/SIZE][/FONT]

Here’s another empirical example of how mutation and selection works, this creature does recombination yet still combination selection pressures slow the ability of this life form to evolve resistance to combination selection pressures.

http://www.biology.ed.ac.uk/research/groups/phunt/profile.php (http://www.biology.ed.ac.uk/research/groups/phunt/profile.php)

If you want to stop evolution, use combination selection pressures.

"Presently, artemisinin and its derivatives are increasingly recommended as first-line anti-malarial therapies, particularly in combination with other drugs, such as amodiaquine, piperaquine, mefloquine and S/P. This strategy is used to increase efficacy and to reduce the probability of resistant parasites surviving and spreading." Where does it mention recombination? It doesn't, because it doesn't matter how variation arises.

Go away and learn some basic evolutionary theory, kleinman. Your knowledge is lacking.

[kleinman]

So, you still haven't done any mathematics, found any evidence, found a counterexample to my model, offered a critique of my model, or grasped how multiple drug therapy works.
It seems that some evolutionarians are getting tired of seeing your silly graph over and over again but we all know it is a fake. So, let’s see this fake again.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Adequate, I think you need to form a new sect of evolutionism. You can call it Multiselectarian Adequarian evolutionism. Your banner can be your silly graph. Here’s another counterexample to your model in which you have yet to post a single example. This example is more than 50 years old.

http://cancerres.aacrjournals.org/cgi/content/abstract/16/7/698 (http://cancerres.aacrjournals.org/cgi/content/abstract/16/7/698)
Resistance to several carcinostatic drugs has been established in neoplastic cells. The resistant variants in the lymphocytic neoplasm L1210, developed in short periods of time through the use of antifolic and antipurine compounds, appear to arise in a discrete, stepwise fashion, resembling the penicillin pattern of microorganisms. In several other lymphocytic neoplasms resistance was developed but not always with ease. It is to be expected, however, that the ease with which the character develops will vary from one neoplasm to another and from one drug to another. Mutation and selection appear to constitute the mechanism involved. The changes are shown to be stable, irreversible, and heritable, and persist in the absence of the drug used in selection. The possibility should not be ignored that the pattern of resistance and the mechanism involved may be quite different in other neoplasms responding to these same compounds.
and
Knowledge that resistance may arise by mutation, that there appears no known method for decreasing mutation rates (although, as mentioned previously, some progress in this direction has been achieved), and that it is unlikely that the host is able to alter the process of spontaneous mutation suggests a familiar and feasible approach, the use of combinations of agents in attempts to eliminate mutants to one drug by means of a second drug simultaneously present. The principle of combined therapy is unusually successful against the L1210 lymphocytic neoplasm with two compounds known to have independence of action, A-methopterin and 8-azaguanine, and in L5178 with A-methopterin plus 6-mercaptopurine. However, it would appear most difficult to predict effective combinations without an understanding of drug interactions involving cross-resistance, collateral sensitivity, synergism, antagonism, etc. Moreover, as shown in bacterial studies, the bacterial species affect, to some extent, the cross-resistance and sensitivity patterns (86). This points up again the danger in generalizing from results gained with a single neoplasm.
More than 50 years ago scientists were seeing the effects of combination selection pressures and what it does to evolution of the life form subjected to these pressures. Of course the Multiselectarian Adequarian Evolutionarians are having trouble comprehending this mathematical and empirical fact but we’ll keep posting their banner.

[krazyKemist]

Now listen krazy, I have to address my comments to the intellectual level of the audience. So let’s consider the Pseudomonas efflux pump. This pump has the capability to pump out a variety of chemically unique and unrelated toxins. Why don’t the Pseudomonas bacteria maintain this pump all the time in its population? Do you think that humans subjecting these bacteria to antibiotics are the first time Pseudomonas ever was subjected to a toxin?

Ah ? The intellectual level of the audience ? People who have to resort to such language in a debate do so when they are quite angry at being contradicted. People who get angry with being contradicted are immature. You can argue with me (and others) simply by giving me reasons why you don't agree to what I say. You don't need to be impolite, or call me stupid, to do so. Being impolite does not give more weight to what you say, it just makes you seem angry, hysterical and immature. I'm sure many people here enjoy seeing a creationist being that way. For me it's simply sad and pathetic.

For pseudomonas now: do I have to explain what metabolic cost is ? Ok, let's try it. Producing a given protein costs energy. What happens if you continue producing it when you don't need it ? Well you spend more energy than your neighbor who doesn't, uselessly. In nature, the amount of energy (calories) you have access to is limited. If you have to spend more than your neighbor you are at a clear disavantage. It's understandable that we humans have forgotten that, since that thanks to agriculture, we live in a calorie-rich environment.

Oh, ev doesn’t explain everything about evolution, but it does explain something about the mathematics of mutation and selection. The things that it does show is what happens when you have multiple selection pressures, profoundly slows the evolutionary process. It also shows what happens to the rate of evolution as you lengthen the genome, it profoundly slows the evolutionary process (if you have multiple selection pressures). It also shows what happens to the rate of evolution as you increase population, it only marginally accelerates the evolutionary process. So what does it explain, it gives a mathematical basis to explain the evolutionary process seen with HIV, HBV, HCV, TB, Malaria, cancer, weeds,… Oh, it does do one additional thing; it shows that mutation and selection can not evolve a reptile to a bird. You have no selection conditions to accomplish this task and you have far to many genes to transform when mutation and selection is only efficient with single selection conditions, especially for slowly reproducing species like reptiles.

If ev doesn't explain everything about evolution, then you can't claim it can prove evolution can't happen, since you don't know the influence of other factors than point mutation over it. That's what I've been saying since the beginning. You may observe a behavior in the specific environment of ev, and quite another in real life. The fact that an "exception" behavior such as the efflux pump exists, it already puts a dent in your assumptions and makes your theory a dangerous oversimplification for medicinal research.

And once again, please define your terms, it will make the discussion much more clearer for everybody. It is not all about the mathematics, but also about biological interpretation of them. For that we need to know exactly what you mean by "slow evolution", "stop evolution", and what you consider to be an adaptation.

This is a very bizarre statement krazy. Not only is it a failure to answer the question of what helicase and replicase were doing before DNA could be replicated, it completely abandons scientific principles. Science examines and attempts to explain cause and affect processes. You have now degraded the theory of evolution to there is no purpose, it just happens. Your ridiculous attempt at an analogy that evolution is like water filling a depression in the ground lacks something, gravity.

You didn't understand my explanation, or the use of the analogy. You are clearly not looking for cause here, but for purpose (what were they doing?). That's an ID question. If you are looking for cause (science) you will ask: How did helicase and replicase get conserved (or selected for, if you prefer) before they evolved to replicate DNA ? And that, is an interesting scientific question. These people are attempting to find out:

http://arep.med.harvard.edu/biophysics/faculty/Szostak96.html

Basically, it is a question of affinity. A protein (or DNA/RNA strand) that is bound to something aquires a different, stabilized conformation (induced-fit). That different conformation may be less vulnerable to denaturation and destruction. Thus, the molecules able to bind are the ones that have longer half-lives, the ones that are conserved. They did not need to have a purpose. And obviously, if they can somehow use the DNA strand to replicate it and itself, well there will be a lot more of them around.

Does anyone knows exactly how that happened ? No. Does that prove that an external source/creator designed them ? If we're doing science, then no. It's not because nobody can't explain exactly what happened today that it can't be explained. Science is about learning new things. It's quite useless to do it if you believe everything is already known, and that what you don't know can be summed up with "God did it". Why are you afraid of things you don't know ?

the Kemist

[kleinman]

Now listen krazy, I have to address my comments to the intellectual level of the audience. So let’s consider the Pseudomonas efflux pump. This pump has the capability to pump out a variety of chemically unique and unrelated toxins. Why don’t the Pseudomonas bacteria maintain this pump all the time in its population? Do you think that humans subjecting these bacteria to antibiotics are the first time Pseudomonas ever was subjected to a toxin?Ah ? The intellectual level of the audience ? People who have to resort to such language in a debate do so when they are quite angry at being contradicted. People who get angry with being contradicted are immature. You can argue with me (and others) simply by giving me reasons why you don't agree to what I say. You don't need to be impolite, or call me stupid, to do so. Being impolite does not give more weight to what you say, it just makes you seem angry, hysterical and immature. I'm sure many people here enjoy seeing a creationist being that way. For me it's simply sad and pathetic.
Oh, did I hurt the feelings of a thin skinned evolutionarian (are there anything else than thin skinned evolutionarians), I’m so sorry, so grow up.
For pseudomonas now: do I have to explain what metabolic cost is ? Ok, let's try it. Producing a given protein costs energy. What happens if you continue producing it when you don't need it ? Well you spend more energy than your neighbor who doesn't, uselessly. In nature, the amount of energy (calories) you have access to is limited. If you have to spend more than your neighbor you are at a clear disavantage. It's understandable that we humans have forgotten that, since that thanks to agriculture, we live in a calorie-rich environment.
You may have to explain what metabolic cost is to the readers of this thread, like joobz. He doesn’t understand that mutation and selection is a restatement of the first law of thermodynamic. Populations which can dedicate the most energy to reproduction are most fit.
Oh, ev doesn’t explain everything about evolution, but it does explain something about the mathematics of mutation and selection. The things that it does show is what happens when you have multiple selection pressures, profoundly slows the evolutionary process. It also shows what happens to the rate of evolution as you lengthen the genome, it profoundly slows the evolutionary process (if you have multiple selection pressures). It also shows what happens to the rate of evolution as you increase population, it only marginally accelerates the evolutionary process. So what does it explain, it gives a mathematical basis to explain the evolutionary process seen with HIV, HBV, HCV, TB, Malaria, cancer, weeds,… Oh, it does do one additional thing; it shows that mutation and selection can not evolve a reptile to a bird. You have no selection conditions to accomplish this task and you have far to many genes to transform when mutation and selection is only efficient with single selection conditions, especially for slowly reproducing species like reptiles.If ev doesn't explain everything about evolution, then you can't claim it can prove evolution can't happen, since you don't know the influence of other factors than point mutation over it. That's what I've been saying since the beginning. You may observe a behavior in the specific environment of ev, and quite another in real life. The fact that an "exception" behavior such as the efflux pump exists, it already puts a dent in your assumptions and makes your theory a dangerous oversimplification for medicinal research.
What ev demonstrates is the fundamental mathematics of mutation and selection. Dr Schneider has successful captured the essential effects of genome size, population, mutation rate and number of selection pressures in his model. I am not claiming evolution can’t happen, what I am claiming is that his model shows what the limitations of mutation and selection are. These limitations are demonstrated by the empirical data. If you study the mathematics of mutation and selection as demonstrated by Dr Schneider’s model, you will see what the effects of varying the different parameters in the model show. What his model shows is that short genome length, large populations with rapid reproduction times and high mutation rates evolve most rapidly. More importantly, the model shows that single selection pressures evolve far more rapidly than combination selection pressures. This is exactly what HIV shows. These mathematical and empirical facts show why it is impossible for large genome populations such as reptiles with slow reproductive rates and low mutation rates can not transform into birds. You don’t have the selection conditions and you don’t have sufficient mutation selection cycles.
And once again, please define your terms, it will make the discussion much more clearer for everybody. It is not all about the mathematics, but also about biological interpretation of them. For that we need to know exactly what you mean by "slow evolution", "stop evolution", and what you consider to be an adaptation.
If you want quantitative values from ev, it takes hundreds of millions of generations to evolve only 100 loci on a 100k genome. If you want empirical data, treating HIV with monotherapy the virus can evolve resistance to that drug in only a few weeks while three drug combination therapy can prevent evolution of resistant viruses for years, even decades. What is clear is that each additional selection pressure slows evolution further. Each additional selection pressure makes it more difficult for the population to traverse the fitness landscape to a new local optimum. This is how mutation and selection actually works.
This is a very bizarre statement krazy. Not only is it a failure to answer the question of what helicase and replicase were doing before DNA could be replicated, it completely abandons scientific principles. Science examines and attempts to explain cause and affect processes. You have now degraded the theory of evolution to there is no purpose, it just happens. Your ridiculous attempt at an analogy that evolution is like water filling a depression in the ground lacks something, gravity.You didn't understand my explanation, or the use of the analogy. You are clearly not looking for cause here, but for purpose (what were they doing?). That's an ID question. If you are looking for cause (science) you will ask: How did helicase and replicase get conserved (or selected for, if you prefer) before they evolved to replicate DNA ? And that, is an interesting scientific question. These people are attempting to find out:
Sure I understand your explanation. Reptiles evolved to birds because water flows into a depression. The only problem with your analogy is that it is gravity that causes water to flow into a depression. What is the force which transforms reptiles into birds? If you answer mutation and selection, then I’ll ask you, what is the selection pressure that would do this? At least Delphi speculated that a temperature change might do this. Then you have to deal with the mathematical and empirical facts of how mutation and selection actually works. The theory of evolution is a very bizarre collection of speculations and unrealistic extrapolations. There is more than enough mathematical and empirical evidence of how mutation and selection actually works to prove that the theory of evolution is impossible.
Basically, it is a question of affinity. A protein (or DNA/RNA strand) that is bound to something aquires a different, stabilized conformation (induced-fit). That different conformation may be less vulnerable to denaturation and destruction. Thus, the molecules able to bind are the ones that have longer half-lives, the ones that are conserved. They did not need to have a purpose. And obviously, if they can somehow use the DNA strand to replicate it and itself, well there will be a lot more of them around.
So now you are going to extrapolate the notion of affinity and speculate that this is how evolution occurs. Biological molecules are inherently unstable. So not only do you have to have proteins form spontaneously but you need the components of DNA to form spontaneously as well. The chemistry of living things is the most complex chemistry known and the idea that proteins and DNA formed spontaneously has no scientific merit. I asked joobz, a professor of chemical engineering if he could describe how ribose could form nonenzymatically. He could not. Even if you could come up with some way of forming ribose nonenzymatically, the ribose molecule is unstable and has a half life of only a few years. If organic molecules are so stable, why do mummies decompose in only a few thousand years despite all the efforts to preserve them? What happens to the tires of your automobile when they are exposed to the sun for a few years? You don’t have a purpose for these molecules to form and you don’t have a cause and effect relationship for these molecules to form.

Here’s a question that I posed on this thread previously but I don’t believe I have asked you. What is the selection pressure that would evolve a gene de novo?
Does anyone knows exactly how that happened ? No. Does that prove that an external source/creator designed them ? If we're doing science, then no. It's not because nobody can't explain exactly what happened today that it can't be explained. Science is about learning new things. It's quite useless to do it if you believe everything is already known, and that what you don't know can be summed up with "God did it". Why are you afraid of things you don't know ?
We do know how mutation and selection works mathematically and we have empirical evidence of how it works and it shows that evolution didn’t do it.

Let me explain to you again how mutation and selection works. Mutation and selection is a sorting problem of beneficial and detrimental mutations. As with all sorting problems, the more sorting conditions imposed the slower the process goes. This type of mathematical behavior is seen in many areas of science and mathematics including system optimization, database sorting and iterative problem solving techniques. Ev demonstrates this phenomenon quite nicely and shows how profoundly slow the process proceeds when you have three selection conditions. This mathematical result is reflected in reality by the numerous citations I have posted. Here is a couple more citations for you to consider.

http://www.medscape.com/viewarticle/550453 (http://www.medscape.com/viewarticle/550453)
Objective: Study 903 was a 144-week, randomized, double-blind, active-controlled study of tenofovir disoproxil fumarate (TDF) therapy in treatment-naive HIV-1-infected patients. Patients received either TDF (n=299) or stavudine (d4T) (n=301) with lamivudine (3TC) and efavirenz (EFV). Resistance analyses were performed at baseline and at virological failure to determine the effects of baseline resistance and the patterns of resistance at virological failure.
Methods: Plasma HIV-1 from patients at baseline and at virological failure (>400 HIV-1 RNA copies/mL at week 144 or early discontinuation) was analysed phenotypically and by population sequencing.
Results: Sixteen per cent of patients were classified as having virological failure (47 on TDF and 49 on d4T; P=0.91). Patients with non-B HIV-1 subtypes or baseline nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations responded similarly to the overall population. Resistance to EFV (K103N and others) or 3TC (M184V) developed most frequently (8.3% and 5.8%, respectively) and similarly in the two arms. In the d4T arm, a variety of NRTI mutations developed: K65R (n=2), L74V (n=2), V75M (n=1), and T69A+Y115H (n=1). K65R developed in eight TDF patients (2.7%); in seven of these eight patients, within 48 weeks. All eight patients began new regimens with a protease inhibitor (PI) and NRTIs, including two patients who remained on TDF; five of the eight patients achieved HIV RNA <50 copies/mL in second-line therapy with the remaining patients having no follow-up or being nonadherent.
Conclusions: Treatment of HIV-1 with TDF, 3TC and EFV was highly effective, with <3% of patients developing resistance to TDF over 144 weeks.

http://www.journals.uchicago.edu/CID/journal/issues/v29n6/990266/990266.html (http://www.journals.uchicago.edu/CID/journal/issues/v29n6/990266/990266.html)
Nucleoside analogues have been used as monotherapy for chronic hepatitis B virus (HBV) infection, and in most cases a rapid drop is seen in the viral load shortly after the start of therapy, to a >90% drop after 48 weeks [1]. Once therapy is stopped, relapses are common, and during prolonged treatment periods the emergence of resistance is common [2]. Recently it was shown that the combination of lamivudine and famciclovir had a synergistic inhibitory effect in vitro in the duck hepatitis virus model [3].
There have been conflicting reports on the activation of endogenous HBV-specific cellular immune responses during nucleoside analogue monotherapy [4, 5], in contrast to those detected during -IFN therapy or spontaneous seroconversion from positivity for hepatitis B early antigen (HBeAg) to positivity for antibodies to HBeAg (anti-HBe) [6, 7]. Since it is generally believed that these responses are of importance in resolving HBV infections, the absence of an activated endogenous cellular immune response during nucleoside monotherapy is consistent with low HBeAg to anti-HBe seroconversion rates [1]. To benefit from a potential synergistic effect and to delay or inhibit the evolution of resistance to lamivudine and famciclovir, combination therapy can be used.
Two more citations which show that combination therapy slow the evolution of resistance. You all consider these findings in light of what the ev computer simulation of random point mutation and natural selection shows. And you all have a good weekend; I’ll be back next week to continue posting the empirical evidence which shows that combination selection pressures slow evolution and how mutation and selection actually works.

[Mr. Scott]

I seem to be sensing that Kleinman believes that god programmed life to adapt (micro-evolve) so it could survive selection pressures. That's why he fails to understand the theory of evolution. He can't set aside his creationist assumptions sufficiently to comprehend what Darwin, Dawkins, et al are saying. I think Kleinman's theory is that god made all the "kinds" of life immutable, except to program a mechanism where life forms can micro-evolve in response to toxins. I think he sees micro-evolution as akin to an organism's immune system. It detects the enemy, and concocts a defense or counter attack in response. Then multiple "pressures" overwhelm this cellular defense mechanism. I think this theory is disprovable and probably has already been disproven. In the century and a half after Darwin created his theory, new species have been observed to arise from others (both plant and animals), new genes have been observed to arise de novo (eg nylon-eating bacteria), and resistance to multiple selection pressures has accumulated (eg gonorrhea) just as Darwinism predicted.

A computer simulation cannot be used to prove something impossible unless it models what it purports to simulate sufficently to be used that way. Ev does not do that. Kleinman has not offered mathematical proof that Ev models evolution well enough to disprove it. Until Kleinman does this, his claim of proof is invalid and can be disregarded.

So, unless Kleinman, proves mathematically that Ev is a sufficient model of evolution to disprove it, he should stop repeating the claim that it is.

I also don't think synergy of antiviral, antibacterial, or antiparasite treatments disproves evolution.

Kleinman has nothing.

[Taffer]

The biggest problem is that kleinman has incorrect assumptions about how the process of natural selection works. He does not grasp that natural selection works on currently existing variation within a population, and it makes no difference whether this variation arose via mutation, recombination, or any other process.

[cyborg]

What kleinman doesn't know could fill a 129 page thread.

Wait a sec...

[Belz...]

If you want to stop evolution, use combination selection pressures.

Evidence ?

Oh, and please don't respond that you've already provided 16,544 proofs for it. I haven't been following the whole thread but it's obvious that, if you HAD proof, you'd be posting IT over and over again rather than spouting your non sequitur endlessly.

I’m so sorry, so grow up.

No, YOU grow up. Stop using insults as arguments. They're no good.

What ev demonstrates is the fundamental mathematics of mutation and selection.

No, it's just a model.

Oh, ev doesn’t explain everything about evolution

Case closed, then.

[Paul C. Anagnostopoulos]

However, Paul assures us of Dr. K's total sincerity.
I do? Did I engage in such armchair psychoanalysis? If so, my bad.

~~ Paul

[Paul C. Anagnostopoulos]

Setting the spurious binding site selection conditions to zero does not mean that every locus in the genome represents a binding site. You may or may not have binding sites at these positions.
That's not what I said. What I said was:

And every other position will also bind to the gene. Do you agree that this is not the same function as the one that evolves when all three pressures are active?
You do understand that the gene can bind positions other than the selected binding sites, right?


But these “spurious” sites only affect the population when you impose the selection condition. Then “spurious” sites affect the fitness of the population. You need to remember something here Paul. Ev is an idealized model of random point mutation and natural selection. Are you going to try an argue that the sequences that ev is evolving represents codons which will actually transcribe to real proteins which will in turn bind to these binding sites? What ev captures is the essential mathematical behavior of the mutation and selection process, not the evolution of binding sites. Ev simple evolves sequences of bases that satisfy the selection conditions. Ev is sorting the mutations such that beneficial mutations get passed on to future generations according to the selection conditions defined.
A most wordy avoidance of the point, Alan.


You and krazyKemist need to get together and get your story straight. He says there is no purpose to evolution and you are saying that evolution must evolve a particular function.
I give up, Alan. Apparently you cannot focus your attention on the points at hand.


Paul, you continue to miss the most important point that your model shows, that is three selection conditions evolve far more slowly than single selection conditions. However, let’s say for discussion that your Rcapacity concept has validity. How would you extend this concept to the mutation and selection process seen with viruses and bacteria? I have already shown and will continue to show how multiple selection conditions slow the evolution of these creatures (and other situations as well).
The Rcapacity problem would only show up in nature if an existing genome suddenly increased in size. As I've said before, Rcapacity is primarily an issue with Ev. But you have to consider it, unless you contend that Ev is, by definition, a completely accurate model of reality.


Well then, you should be able to demonstrate empirical examples of this. We already have huge volumes of empirical evidence of how mutation and selection actually works and it is not evolving binding sites. What ev is demonstrating is that particular sequences of bases can evolve at particular positions of the genome and this process becomes profoundly slow when you have multiple selection conditions evolving simultaneously on realistic length genomes. This effect is seen over and over in the empirical evidence, two more citations are posted below.
It appears that sentence 2 contradicts sentence 4.

~~ Paul

[krazyKemist]

Oh, did I hurt the feelings of a thin skinned evolutionarian (are there anything else than thin skinned evolutionarians), I’m so sorry, so grow up.

Did I say that your insults hurt my or anyone else's feelings ? No. I just said that the way you are expressing yourself make you look angry, immature and hysterical. You like that ? Fine, be that way. Your choice.

You may have to explain what metabolic cost is to the readers of this thread, like joobz. He doesn’t understand that mutation and selection is a restatement of the first law of thermodynamic. Populations which can dedicate the most energy to reproduction are most fit.

Let's see (again) what the first law of thermodynamics is, shall we ?

The increase in the internal energy of a thermodynamic system is equal to the amount of heat energy added to the system minus the work done by the system on the surroundings.

Please explain to me how this is related to the process of mutation and selection. Or the concept of metabolic cost. To me, this speaks about energy, and the ways it can be transformed into work and heat. What we're talking about is calorie restriction, and how it can play a role as a selection pressure. If you remove/lessen calorie restriction, what happens ? Remember, there are different solution for a given problem. We humans for example reproduce very poorly compared to lemmings. Does that mean we're less fit ? Seeing our actual progression, I doubt it.

What ev demonstrates is the fundamental mathematics of mutation and selection. Dr Schneider has successful captured the essential effects of genome size, population, mutation rate and number of selection pressures in his model. I am not claiming evolution can’t happen, what I am claiming is that his model shows what the limitations of mutation and selection are. These limitations are demonstrated by the empirical data. If you study the mathematics of mutation and selection as demonstrated by Dr Schneider’s model, you will see what the effects of varying the different parameters in the model show. What his model shows is that short genome length, large populations with rapid reproduction times and high mutation rates evolve most rapidly. More importantly, the model shows that single selection pressures evolve far more rapidly than combination selection pressures. This is exactly what HIV shows. These mathematical and empirical facts show why it is impossible for large genome populations such as reptiles with slow reproductive rates and low mutation rates can not transform into birds. You don’t have the selection conditions and you don’t have sufficient mutation selection cycles.

Blah, blah, blah... Please stop repeating always the same information. And relating to HIV, please explain to me why, if your model states that "evolution can stop" with only 3 selection pressures (which you somehow equate with the number of antivirals for HIV, feel free to correct me if I'm wrong there), HIV cannot be eradicated despite the more than 20 antivirals available to date. More than that, how it manages to develop resistance to HAART.

If you want quantitative values from ev, it takes hundreds of millions of generations to evolve only 100 loci on a 100k genome. If you want empirical data, treating HIV with monotherapy the virus can evolve resistance to that drug in only a few weeks while three drug combination therapy can prevent evolution of resistant viruses for years, even decades. What is clear is that each additional selection pressure slows evolution further. Each additional selection pressure makes it more difficult for the population to traverse the fitness landscape to a new local optimum. This is how mutation and selection actually works.

What happens when you increase the total weight of the selection pressures combined (whether with one or several selection pressures) ? Well, there is a definite drop in population. This is measured using quantitative PCR of viral charge for HIV. If there are less individuals, and the same mutation rate is conserved, then there are much less chances that the "winning combination" be achieved. Since using extra high doses of antiviral is harmfully toxic, we rely on their synergy to gain an advantage in toxicity.

Another analogy (p.s.: an analogy is not exactly the thing it tries to explain, if you see what I mean ;) ): if you buy 100 lottery tickets, you have better chances of winning than if you buy just 1, do we agree on that ? So if you have, say, a population X times higher, don't you have X times more chances of getting the right mutations ? If not, please explain me why, using mathematical equations.

Sure I understand your explanation. Reptiles evolved to birds because water flows into a depression. The only problem with your analogy is that it is gravity that causes water to flow into a depression. What is the force which transforms reptiles into birds? If you answer mutation and selection, then I’ll ask you, what is the selection pressure that would do this? At least Delphi speculated that a temperature change might do this. Then you have to deal with the mathematical and empirical facts of how mutation and selection actually works. The theory of evolution is a very bizarre collection of speculations and unrealistic extrapolations. There is more than enough mathematical and empirical evidence of how mutation and selection actually works to prove that the theory of evolution is impossible.

And... No you don't. You are cligning to an ID definition of evolution. And you are now misusing my analogy, as it is one favorite habits of yours.

So now you are going to extrapolate the notion of affinity and speculate that this is how evolution occurs. Biological molecules are inherently unstable. So not only do you have to have proteins form spontaneously but you need the components of DNA to form spontaneously as well. The chemistry of living things is the most complex chemistry known and the idea that proteins and DNA formed spontaneously has no scientific merit. I asked joobz, a professor of chemical engineering if he could describe how ribose could form nonenzymatically. He could not. Even if you could come up with some way of forming ribose nonenzymatically, the ribose molecule is unstable and has a half life of only a few years. If organic molecules are so stable, why do mummies decompose in only a few thousand years despite all the efforts to preserve them? What happens to the tires of your automobile when they are exposed to the sun for a few years? You don’t have a purpose for these molecules to form and you don’t have a cause and effect relationship for these molecules to form.

You find that hard to believe ? Ok then. There are a couple people at Scripps applying just what principles I described to develop new drugs. The system is simple. They use a well-known chemical reaction at equilibrium (with the products forming and being reversibly destroyed to the starting reagents). Then they put their target enzyme (loaded onto a solid support) into the reaction media. They let the reaction go on for a couple hours. They filtrate the bead-loaded enzyme out of the reaction. Surprise ! It contains molecules which have a high affinity to the enzyme. Why ? Because they they were protected from destruction by binding to the enzyme. If we can do it in a test tube, can't it happen in nature ? If not, why ? The same laws of physics apply everywhere.

And still you are looking for purpose, which you equate to cause. They are not the same thing. Let's look at the definitions:

cause: a reason for an action or condition : motive : something that brings about an effect or a result c: a person or thing that is the occasion of an action or state; especially : an agent that brings something about d: sufficient reason. discharged for cause.

purpose: something set up as an object or end to be attained; a subject under discussion or an action in course of execution; synonyms: see intention.

They are slightly different, aren't they ? Behind the purpose, there is intention. As in someone/something intends things to be so. You don't look for anybody behind cause (except in the legal/trial sense, of course).

Here’s a question that I posed on this thread previously but I don’t believe I have asked you. What is the selection pressure that would evolve a gene de novo?

Are you confusing terms on purpose ? Let's be clear then: mutations do not originate from selection pressures, but from factors of the environment which cause replication mistakes. How could a gene appear de novo ? Well, not by point mutation alone. Those other mechanisms, which you seem to find so unimportant, are involved. Genes get duplicated. Even whole chromosomes can get duplicated. Once that done, let them evolve (accumulate mutations through time) their separate ways. You will get different genes. Why ? Because there is no purpose, no target as such for evolution. Mutations happen randomly, meaning a different outcome is possible each time you try it. But of course, if you insist on confusing cause and purpose, then that explanation was a waste of time.

Let me explain to you again how mutation and selection works. Mutation and selection is a sorting problem of beneficial and detrimental mutations. As with all sorting problems, the more sorting conditions imposed the slower the process goes. This type of mathematical behavior is seen in many areas of science and mathematics including system optimization, database sorting and iterative problem solving techniques. Ev demonstrates this phenomenon quite nicely and shows how profoundly slow the process proceeds when you have three selection conditions. This mathematical result is reflected in reality by the numerous citations I have posted. Here is a couple more citations for you to consider.

And you are again repeating the same thing. As in every post. Please read this and remember: I (krazyKemist) do not object to combined therapy. There. I hope we at least make this clear.

Again, define your terms clearly, as in like what you see in a dictionnary. We'll begin by discussing these, and that will allow us to progress.

Have an good week-end.

the Kemist

[Dr Adequate]

It seems that some evolutionarians are getting tired of seeing your silly graph over and over again but we all know it is a fake. This is an interesting lie.

Who, exactly, do you claim shares your fantasy world?

If anyone agrees with kleinman that the data from my model is "fake", please feel free to speak out.

[Dr Adequate]

Oh, did I hurt the feelings of a thin skinned evolutionarian (are there anything else than thin skinned evolutionarians), I’m so sorry, so grow up.

You may have to explain what metabolic cost is to the readers of this thread, like joobz. He doesn’t understand that mutation and selection is a restatement of the first law of thermodynamic. Populations which can dedicate the most energy to reproduction are most fit.

What ev demonstrates is the fundamental mathematics of mutation and selection. Dr Schneider has successful captured the essential effects of genome size, population, mutation rate and number of selection pressures in his model. I am not claiming evolution can’t happen, what I am claiming is that his model shows what the limitations of mutation and selection are. These limitations are demonstrated by the empirical data. If you study the mathematics of mutation and selection as demonstrated by Dr Schneider’s model, you will see what the effects of varying the different parameters in the model show. What his model shows is that short genome length, large populations with rapid reproduction times and high mutation rates evolve most rapidly. More importantly, the model shows that single selection pressures evolve far more rapidly than combination selection pressures. This is exactly what HIV shows. These mathematical and empirical facts show why it is impossible for large genome populations such as reptiles with slow reproductive rates and low mutation rates can not transform into birds. You don’t have the selection conditions and you don’t have sufficient mutation selection cycles.

If you want quantitative values from ev, it takes hundreds of millions of generations to evolve only 100 loci on a 100k genome. If you want empirical data, treating HIV with monotherapy the virus can evolve resistance to that drug in only a few weeks while three drug combination therapy can prevent evolution of resistant viruses for years, even decades. What is clear is that each additional selection pressure slows evolution further. Each additional selection pressure makes it more difficult for the population to traverse the fitness landscape to a new local optimum. This is how mutation and selection actually works.

Sure I understand your explanation. Reptiles evolved to birds because water flows into a depression. The only problem with your analogy is that it is gravity that causes water to flow into a depression. What is the force which transforms reptiles into birds? If you answer mutation and selection, then I’ll ask you, what is the selection pressure that would do this? At least Delphi speculated that a temperature change might do this. Then you have to deal with the mathematical and empirical facts of how mutation and selection actually works. The theory of evolution is a very bizarre collection of speculations and unrealistic extrapolations. There is more than enough mathematical and empirical evidence of how mutation and selection actually works to prove that the theory of evolution is impossible.

So now you are going to extrapolate the notion of affinity and speculate that this is how evolution occurs. Biological molecules are inherently unstable. So not only do you have to have proteins form spontaneously but you need the components of DNA to form spontaneously as well. The chemistry of living things is the most complex chemistry known and the idea that proteins and DNA formed spontaneously has no scientific merit. I asked joobz, a professor of chemical engineering if he could describe how ribose could form nonenzymatically. He could not. Even if you could come up with some way of forming ribose nonenzymatically, the ribose molecule is unstable and has a half life of only a few years. If organic molecules are so stable, why do mummies decompose in only a few thousand years despite all the efforts to preserve them? What happens to the tires of your automobile when they are exposed to the sun for a few years? You don’t have a purpose for these molecules to form and you don’t have a cause and effect relationship for these molecules to form.

Here’s a question that I posed on this thread previously but I don’t believe I have asked you. What is the selection pressure that would evolve a gene de novo?

We do know how mutation and selection works mathematically and we have empirical evidence of how it works and it shows that evolution didn’t do it.

Let me explain to you again how mutation and selection works. Mutation and selection is a sorting problem of beneficial and detrimental mutations. As with all sorting problems, the more sorting conditions imposed the slower the process goes. This type of mathematical behavior is seen in many areas of science and mathematics including system optimization, database sorting and iterative problem solving techniques. Ev demonstrates this phenomenon quite nicely and shows how profoundly slow the process proceeds when you have three selection conditions. This mathematical result is reflected in reality by the numerous citations I have posted. Here is a couple more citations for you to consider.

http://www.medscape.com/viewarticle/550453 (http://www.medscape.com/viewarticle/550453)


http://www.journals.uchicago.edu/CID/journal/issues/v29n6/990266/990266.html (http://www.journals.uchicago.edu/CID/journal/issues/v29n6/990266/990266.html)

Two more citations which show that combination therapy slow the evolution of resistance. You all consider these findings in light of what the ev computer simulation of random point mutation and natural selection shows. And you all have a good weekend; I’ll be back next week to continue posting the empirical evidence which shows that combination selection pressures slow evolution and how mutation and selection actually works. This doesn't contain any new lies.

However, the pompous way in which you tell the lie about thermodynamics still makes me smile.

Is there anything you're not totally ignorant about?

[quixotecoyote]

Well, his grammar is relatively decent.

[Anacoluthon64]

And he's a consummate, though somewhat repetitive, derider. Adept at deceit, too.

'Luthon64

[Dr Adequate]

Adept at deceit, too. Er ... but he hasn't actuallly succeeded in deceiving anyone.

He's a failed liar.

[quixotecoyote]

Doh! Beaten to the punch.

[Dr Adequate]

The reason he can’t post an example of this is his graph is a fake. A "fake" which anyone can replicate by running the publicly available code.

Well, almost anyone. Obviously you can't, 'cos of your mental problems.

The contrast between our two views could not be starker. Indeed. I'm telling the truth to an audience that knows I'm telling the truth, and can check that I'm telling the truth whenever they wish; you're reciting witless bullcrap like this:

I have a peer reviewed and published model of mutation and selection which supports my view point and I have posted over 100 examples of this while Adequate has his own silly graph and no real examples of his viewpoint. So prepare yourself to see Adequate’s graph over and over until he either posts a citation which demonstrates his allegation or he admits his graph is a fake. ... to an audience which, to a man, knows you to be a demented liar.

[Dr Adequate]

You also make the claim that it will take longer to evolve 3 traits in parallel then in series. But think about how mutation occurs. The mutation rate at one locus can be given by μ. So, if 3 mutation events are to occur in series, we would expect a frequency of μ*μ*μ, or μ^3. If they are to occur in parallel, we would expect the same frequency. Why? Because each mutation event is independant of the other. Thus, just as many mutation events are happening, whether it is in parallel or series. Thus, it makes not difference to the "time it takes for 3 antibacterials to evolve" whether they appear one after another, or whether they appear all at once. Hold on a minute.

What you're missing is that in the parallel case, it doesn't matter which order the mutations appear in, whereas in the sequential case it does.

This is how I was able to predict the results of my model before I wrote it:

An unordered set of chance events will come up quicker than the same set in some specified order.

Hence we should expect simultaneous selection pressures to fix a given set of adaptive mutations faster then the same pressures acting in sequence, so long as the population sizes are the same, i.e. the selective pressures on the individual are not demographic pressures on the population. I agree with the rest of your analysis.

[Anacoluthon64]

Er ... but he hasn't actuallly succeeded in deceiving anyone.In my haste to find something - anything - redeeming, I neglected to prepend "self-" to "deceit."

I hope that clears matters up.

'Luthon64

[Taffer]

Hold on a minute.

What you're missing is that in the parallel case, it doesn't matter which order the mutations appear in, whereas in the sequential case it does.

This is how I was able to predict the results of my model before I wrote it:

I agree with the rest of your analysis.

Granted. However, it should not make a difference if the overall "goal" is having resistance to all three. At least, I wouldn't think it would.

[joobz]

You may have to explain what metabolic cost is to the readers of this thread, like joobz. He doesn’t understand that mutation and selection is a restatement of the first law of thermodynamic. Populations which can dedicate the most energy to reproduction are most fit.
WOW! thank you.
I completely forgot about the "Natural selection is a restatement..." nonsense.

I was just remembering your claims of
that thermodynamics is a kinetic study ("dynamics is in the name!!!")
silly, silly, kleinman.


Can you also re-inform us on how you exceed probabilities of 1?

[joobz]

Granted. However, it should not make a difference if the overall "goal" is having resistance to all three. At least, I wouldn't think it would.

Yes, but this was the "low hanging fruit" that has been dangling in front of Kleinman this entire time. I'm certain Dr. A has been laughing to himself over Kleinman's inability to talk about it. He could have addressed this limitation if he actually understood the model or could run it(neither of which were demonstrated).

[Dr Adequate]

Granted. However, it should not make a difference if the overall "goal" is having resistance to all three. At least, I wouldn't think it would. Think again.

To make it easier, consider an idealised case in which there is no genetic drift, so that if a mutation occurs, and the selection pressure is operating, it will become fixed, and if it isn't, it won't.

Then applying the selection pressures sequentially and cumulatively is like rolling a die until the numbers from 1 to 6 have come up in that order:

53434252613434324121213511355256412122344243341525 32432236 ...

Whereas if the pressures are applied simultaneously, that's like trying to roll the numbers from 1 to 6 in any order:

53434252613434324121213511355256412122344243341525 32432236 ...

The average time of the second method is clearly going to be quicker; to prove this rigorously we have only to observe that sequences satisfying the first selection method also necessarily satisfy the second, but that the converse is not true.

[delphi_ote]

There are some pretty sophisticated complications in these hypothetical multiple selection pressure scenarios. Remember that it's entirely possible the pressures could interfere in convoluted ways. The components of a system that add up to an adaptation that addresses all of the pressures might simultaneously each independently be worse for the organism under all of the selection pressures. It's also possible that multiple adaptations that address other selection pressures might combine under new selection pressures to form a totally new adaptation. All of the adaptations that eventually led to flight would be a very good example of this.

Just remember that this fitness landscape concept can be very counterintuitive sometimes. Be careful about assuming, because there's almost always an exception.

[Dr Adequate]

There are some pretty sophisticated complications in these hypothetical multiple selection pressure scenarios. Remember that it's entirely possible the pressures could interfere in convoluted ways. You should bear in mind that we're comparing simultaneous selection with cumulative sequential selection, i.e. at the end of the sequential process, exactly the same selection pressures obtain as are present throughout the simultaneous process. It might be that two mutations, each good in itself, interact to be lethal (the simplest case, I think, of what you're talking about) --- in which case a viable organism having both mutations can't be produced by either method.

[delphi_ote]

You should bear in mind that we're comparing simultaneous selection with cumulative sequential selection, i.e. at the end of the sequential process, exactly the same selection pressures obtain as are present throughout the simultaneous process. It might be that two mutations, each good in itself, interact to be lethal (the simplest case, I think, of what you're talking about) --- in which case a viable organism having both mutations can't be produced by either method.
I was more trying to remind people to keep the real world context in mind. There's no one specific series of "correct" mutations in the natural world under either scenario. Basically, we're dealing with an optimization problem where the function being optimized is either changing over time or is static, but the final optima are the same.

Cumulative sequential selection may present the population with a possible adaptation that works extremely well, but is terrible when another selection pressure is added. The population probably won't be able to adapt to the new pressure. It's stuck in an evolutionary dead end. If the population had been presented with all of the selection pressures from the beginning, it obviously would have taken a totally different evolutionary direction.

The opposite scenario is also possible. The sequential series selection pressures may allow the population to gradually adapt to an environment that would otherwise be inhospitable. It all depends on how the fitness landscape changes with the added selection pressures.

[Dr Adequate]

The opposite scenario is also possible. The sequential series selection pressures may allow the population to gradually adapt to an environment that would otherwise be inhospitable. But this is only an issue when the pressures are demographic pressures on the population as well as selective pressures on the individual. The whole point of my model is to separate the two effects.

If, for example, we halved the population for every pressure present and not yet adapted to, then we might very well see a completely different story. But that's not what I'm modelling.

[delphi_ote]

But this is only an issue when the pressures are demographic pressures on the population as well as selective pressures on the individual. The whole point of my model is to separate the two effects.
I don't think I understand what you mean by this. Basically, I'm trying to say that it is possible on a dynamic fitness landscape that the probability of one adaptive mutation happening is conditional based on the presence of another adaptive mutation.

[kjkent1]

Sorry to interrupt the dialog, but it seems to me that everyone presumes that selection is the engine of evolutionary change, rather than mutation.

It seems to me that selection just refines a mutation to suit an existing environment, but the mutation itself is, by definition, entirely unpredictable, and frequently quite dramatic, because there's no reason why it must "fit" the environment when it first arises.

For instance, suppose a creature mutates webbed feet in a desert environment. Not particularly useful, and over time, the mutation may atrophy. But, if the environment becomes wetter, such as if a colony of creatures migrates and finds itself confronted with a river that it previously couldn't have crossed -- then all of a sudden, the webbed mutation is more valuable.

Point being that the various mathematical models tend to treat each mutation as no more valuable than any other. When in reality, some mutations are enormously more valuable, and send a species spinning off in en entirely unexpected direction.

All of which leads me to find that while models like ev show how evolution works, they don't show how dramatically evolution works.

Case study for me right now is Mr. Daniel Tammet. His intelligence is different from the typical genius, because he can do things that aren't just intelligent -- they're seemingly impossible.

So, if Tammet's genes reproduce into the general population, the humans who acquire his talents will not "fit" within the scope of things that ordinary IQ tests test. These people will be catagorically different -- not human, by human standards. Not necessarily more intelligent than Einstein or Bach, but substantially better at certain intellectual talents that will set them apart from the norm, and will take them to an entirely different fitness landscape.

OK, nuff said, please resume your discussion.

[Taffer]

Think again.

To make it easier, consider an idealised case in which there is no genetic drift, so that if a mutation occurs, and the selection pressure is operating, it will become fixed, and if it isn't, it won't.

Then applying the selection pressures sequentially and cumulatively is like rolling a die until the numbers from 1 to 6 have come up in that order:

53434252613434324121213511355256412122344243341525 32432236 ...

Whereas if the pressures are applied simultaneously, that's like trying to roll the numbers from 1 to 6 in any order:

53434252613434324121213511355256412122344243341525 32432236 ...

The average time of the second method is clearly going to be quicker; to prove this rigorously we have only to observe that sequences satisfying the first selection method also necessarily satisfy the second, but that the converse is not true.

Ah, I see your point. I also see what I did wrong.

I was not considering selection pressures, y'see. I was pointing out that the time for a mutation to arise is unrelated to any other mutation, and thus is the same whether they occur all at once or one after another. However, I had worded that paragraph particularly poorly. My intention was to relate it to the mathematical model I had given above which shows that increased selection speeds up the rate of evolutionary change, and the other paragraph pointing out that, for natural selection to select for a particular trait, that trait must exist in a given population. As loci are (generally) mutationally isolated from one another, the frequency at which a series of mutations arise should be the same. However, when combined with selection, it is another matter.

That said, you are quite correct that evolving using the stronger selection of multiple, parallel, pressures will, indeed, cause multiple alleles to fix much faster then when they are applied in series.

[Dr Adequate]

I don't think I understand what you mean by this. Basically, I'm trying to say that it is possible on a dynamic fitness landscape that the probability of one adaptive mutation happening is conditional based on the presence of another adaptive mutation. Of it happening? Don't you mean "of it being favored by natural selection"?

Yes, of course such a situation can exist, in which case the selection pressures for the two mutations are de facto cumulative sequential. Whereas if the success of the second mutation was not contingent on the presence of the first, then the selection pressures would be simultaneous, and the "goal" would be reached quicker.

[Dr Adequate]

Sorry to interrupt the dialog, but it seems to me that everyone presumes that selection is the engine of evolutionary change, rather than mutation. It doesn't seem that way to me.

Point being that the various mathematical models tend to treat each mutation as no more valuable than any other. When in reality, some mutations are enormously more valuable, and send a species spinning off in en entirely unexpected direction. In my model, I took all the selection pressures to have the same intensity 'cos then if I'd done the simulation right, the graph for the sequential selection pressures would be (indistiguishable from) a straight line, which looks nice and provided a check that I'd done the simulation properly. However, you will find that if you remove this feature from the model, the qualitative result will be the same.

[delphi_ote]

Of it happening? Don't you mean "of it being favored by natural selection"?
The probability that a mutation will occur in a population depends on the contents of its genomes. If a beneficial mutation is requires a dramatic change from what has already evolved, it is unlikely to happen. If different adaptation for the selection pressure requires less dramatic changes, it's more likely the population will end up with the mutations for that adaptation.
Yes, of course such a situation can exist, in which case the selection pressures for the two mutations are de facto cumulative sequential. Whereas if the success of the second mutation was not contingent on the presence of the first, then the selection pressures would be simultaneous, and the "goal" would be reached quicker.
The interference can go both ways. The presence of a beneficial mutation for the first adaptation can make the probability of a mutation for the second happening more or less likely. This all depends on how the fitness landscape shifts the local optima around and which local optima the population "finds."

[Dr Adequate]

The probability that a mutation will occur in a population depends on the contents of its genomes. If a beneficial mutation is requires a dramatic change from what has already evolved, it is unlikely to happen. If different adaptation for the selection pressure requires less dramatic changes, it's more likely the population will end up with the mutations for that adaptation. This is of course perfectly true, but I don't see what it has to do with the interaction of two adaptations to different selection pressures.

The interference can go both ways. The presence of a beneficial mutation for the first adaptation can make the probability of a mutation for the second happening more or less likely. This all depends on how the fitness landscape shifts the local optima around and which local optima the population "finds." I still don't see what you're getting at. The presence of a mutation on one part of the genome can't make the occurence of a mutation on another part of the genome more or less likely (unless, I suppose, the first mutation damages the proofreading/error correction mechanism.) Mutations are random.

---

You also seem to be talking as if the fitness landscape varied with the genome of the organism. It doesn't. The organism's position on the fitness landscape varies with its genome: the landscape itself varies with the environment.

[delphi_ote]

I still don't see what you're getting at. The presence of a mutation on one part of the genome can't make the occurence of a mutation on another part of the genome more or less likely (unless, I suppose, the first mutation damages the proofreading/error correction mechanism.) Mutations are random.

I think I see where our difference is. I'm talking about variable length genomes and mutations that consist of more than a single point mutation. Tandem duplications, for example, can make the probability of a subsequent mutation happening depend heavily on the presence of a prior mutation.

[Soapy Sam]

Evolution is about adaptation to an environment.
Selection can occur because the genome changes- or because the environment changes. It's perfectly possible for two species, one slightly better adapted than the other, to "change places" in the "best adapted stakes" without either experiencing any genetic shift whatever.
All this requires is a change in the ambient environment- which may mean a change in a third species , perhaps a predator or prey species.

It's a bloody complicated jungle out there.

[Dr Adequate]

I think I see where our difference is. I'm talking about variable length genomes and mutations that consist of more than a single point mutation. Tandem duplications, for example, can make the probability of a subsequent mutation happening depend heavily on the presence of a prior mutation. Fair enough. In that case, again, the selection pressures are de facto sequential (if there is a selective advantage associated with the duplication; it may well be neutral.)

[joobz]

Think again.

To make it easier, consider an idealised case in which there is no genetic drift, so that if a mutation occurs, and the selection pressure is operating, it will become fixed, and if it isn't, it won't.
By why would a mutation beneficial for future selections but with no effect on current pressures be completely lost from the population?

[kleinman]

So, you mathematically challenged evolutionarians are still unable to shed much light on how mutation and selection actually works. Well, let’s see if we can help illuminate you and your bizarre interpretation of the mathematical and empirical facts of how this phenomenon actually works.
A computer simulation cannot be used to prove something impossible unless it models what it purports to simulate sufficently to be used that way. Ev does not do that. Kleinman has not offered mathematical proof that Ev models evolution well enough to disprove it. Until Kleinman does this, his claim of proof is invalid and can be disregarded.

So, unless Kleinman, proves mathematically that Ev is a sufficient model of evolution to disprove it, he should stop repeating the claim that it is.
Now pussycat, the author of the program, Dr Tom Schneider of the National Cancer Institute purports that his model simulates the important essentials of the mutation and selection process and I agree with the author. The peer reviewer at the Oxford University Press Journal Nucleic Acids Research agreed enough with Dr Schneider to publish the results of his model and have now posted more than 100 citations which confirms the results from his model. I know this entirely contradicts your evolutionarian belief system and denial is the only way for you evolutionarians to deal with these mathematical and empirical facts but sorry pussycat, facts are facts. Since you don’t want to discuss the mathematics or empirical facts of mutation and selection, perhaps you would like to talk about the lies your parents told you.
The biggest problem is that kleinman has incorrect assumptions about how the process of natural selection works. He does not grasp that natural selection works on currently existing variation within a population, and it makes no difference whether this variation arose via mutation, recombination, or any other process.
Taffer, you can’t tell the difference between mutation and selection and recombination and selection. Both are sorting problems. Mutation and selection is the sorting of beneficial and detrimental mutations while recombination and selection is the sorting of beneficial and detrimental alleles. One of the reason sorting of mutation and selection becomes so profoundly slow is the 4^G search space while recombination and selection has a much smaller search space because of the much, much smaller number of alleles that are being sorting. In addition, mating is often not random in the recombination and selection process giving even much more rapid morphological changes in the population. Dog breeding demonstrates this phenomenon. If you don’t like this example because of human involvement in the selection process, take Darwin’s own example of the variations of finch beaks which also demonstrates this phenomenon. Since you are having a hard time understanding the difference between mutation and selection and recombination and selection, here is a citation from a professor at Rice University.
http://www.rice.edu/sallyport/2007/winter/features/evolution.html (http://www.rice.edu/sallyport/2007/winter/features/evolution.html)
“Nature has to have a variety of ways to facilitate change if it’s going to win the numbers game,” says Joff Silberg, assistant professor of biochemistry and cell biology. Proteins, which power all biomolecular processes, are built by combining any of the 20 amino acids found in nature. Given that bacterial proteins are around 300 amino acids long, some 20^300 possible combinations of amino acids can be made. For perspective, a pile of unique protein sequences with the same mass as the Earth would only contain 1050 proteins. Somehow, within this vast sequence space, nature must find functional proteins to catalyze reactions, transport materials, and build larger biomolecular structures. Evolutionary studies investigate how nature accomplishes this feat and, more importantly, how humans can co-opt these processes in the search for unique protein functions.

Mutation may be the most well-known method of generating new functionality, but it is not the most efficient. In laboratory studies, Silberg has quantified a mutational landscape for proteins that shows function sliding down an exponential cliff—the more mutations in a protein, the less likely that protein is to retain useful function. Mutation, says Silberg, is fine for making minor tweaks to a working system, either in an organism or in the lab, but bigger changes require larger, more drastic moves.

Enter horizontal gene transfer, such as that employed by the bacillus in Cuatro Ciénegas, and recombination. Silberg likens recombination to “taking the left front leg off an African elephant and swapping it with one off an Asian elephant—they are different beasts, but they do the same kind of business.” While this type of wholesale change seems artificial, nature regularly employs it to recruit specific structural features for necessary tasks. Moreover, Silberg has found that libraries of proteins created by recombination provide more functional diversity than libraries produced by mutation.
Professor Silberg understands how slow the sorting process for mutation and selection is and if a population needs to respond rapidly to a selection pressure, recombination is much more rapid.

Taffer, you also don’t understand that recombination without error can not create new information (alleles) in the gene pool and that recombination with natural selection can cause the loss of information (alleles) from the gene pool. Recombination with natural selection can not transform reptiles into birds. You need mutation and natural selection to make this metamorphosis. However, mutation and natural selection is profoundly slow if you have combination selection pressures, especially if you have small populations with slow reproductive times.
What kleinman doesn't know could fill a 129 page thread.
Why cyborg, what I don’t know would fill far more than 129 pages, but what I do know about mutation and selection will fill such a thread. In all fairness, if we removed the evolutionarian cruft, this thread would be much shorter.
If you want to stop evolution, use combination selection pressures.Evidence ?

Oh, and please don't respond that you've already provided 16,544 proofs for it. I haven't been following the whole thread but it's obvious that, if you HAD proof, you'd be posting IT over and over again rather than spouting your non sequitur endlessly.
Belz, I know you are confused by Dr Schneider’s mathematical model of mutation and selection and the numerous citations of real examples of mutation and selection conflict so completely with your evolutionarian belief system that you have gone into denial of what these empirical examples of mutation and selection are showing but in time, you will come to understand how mutation and selection actually works. I will continue to post more empirical examples of how mutation and selection actually works while we can wait for an eternity for a single example from you evolutionarians of multiple selection pressures accelerating evolution. The phenomenon of mutation and selection is far too important in multiple areas of medicine and science to let you evolutionarians put your strange and bizarre interpretations which block scientific and medical advancement.
However, Paul assures us of Dr. K's total sincerity.I do? Did I engage in such armchair psychoanalysis? If so, my bad.
You evolutionarians are looking for any way you can to deny the mathematical and empirical facts of how mutation and selection actually works. Do you think you can decide that if I am insincere that the mathematical and empirical facts of mutation and selection are no longer valid? I keep telling you; one of the four cardinal symptoms of evolutionism is denialophilia.
Setting the spurious binding site selection conditions to zero does not mean that every locus in the genome represents a binding site. You may or may not have binding sites at these positions.That's not what I said. What I said was:And every other position will also bind to the gene. Do you agree that this is not the same function as the one that evolves when all three pressures are active?You do understand that the gene can bind positions other than the selected binding sites, right?
Certainly I understand that you can have mutations anywhere in the genome that might lead to a match with the weight matrix. However, if I understand your selection condition for locating binding sites only count as mistakes when a binding site is not identified where one should occur. Any weight matrix matches which might occur outside the binding sites when using only the binding site location selection condition it being applied will not affect selection of creatures. There is no reason to believe that the entire genome will evolve to binding sites.

Paul, the only function for selection is to evolve sequences of bases that improve the fitness of the population to reproduce. Are you going to propose that Dr Schneider’s model evolves real sequences of bases that will produce transcribed proteins that will bind to these sequences in reality?
You and krazyKemist need to get together and get your story straight. He says there is no purpose to evolution and you are saying that evolution must evolve a particular function.I give up, Alan. Apparently you cannot focus your attention on the points at hand.
Paul, I know exactly what the point at hand is. That point is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process. Your own computer simulation shows this and the empirical data shows this. You are working very hard to squirm out of this mathematical and empirical fact but it isn’t going to happen. Your only choice is to go into denial of this mathematical and empirical fact. Your evolutionarian belief system impairs your ability to understand these mathematical and empirical facts.
Paul, you continue to miss the most important point that your model shows, that is three selection conditions evolve far more slowly than single selection conditions. However, let’s say for discussion that your Rcapacity concept has validity. How would you extend this concept to the mutation and selection process seen with viruses and bacteria? I have already shown and will continue to show how multiple selection conditions slow the evolution of these creatures (and other situations as well).The Rcapacity problem would only show up in nature if an existing genome suddenly increased in size. As I've said before, Rcapacity is primarily an issue with Ev. But you have to consider it, unless you contend that Ev is, by definition, a completely accurate model of reality.
Paul, there is no Rcapacity problem; the only problem you evolutionarians have is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process. Your own computer model shows this and the empirical data shows this. What I contend about ev is that it is an idealize model of random point mutation and natural selection that properly captures the mathematical behavior of the effects of genome length, population, number of selection pressures and several other parameters of the mutation and selection process. Ev does not simulate the evolution of real binding sites.
Well then, you should be able to demonstrate empirical examples of this. We already have huge volumes of empirical evidence of how mutation and selection actually works and it is not evolving binding sites. What ev is demonstrating is that particular sequences of bases can evolve at particular positions of the genome and this process becomes profoundly slow when you have multiple selection conditions evolving simultaneously on realistic length genomes. This effect is seen over and over in the empirical evidence, two more citations are posted below.It appears that sentence 2 contradicts sentence 4.
Paul, do you believe the ev is evolving real binding sites?
You may have to explain what metabolic cost is to the readers of this thread, like joobz. He doesn’t understand that mutation and selection is a restatement of the first law of thermodynamic. Populations which can dedicate the most energy to reproduction are most fit.Let's see (again) what the first law of thermodynamics is, shall we ?The increase in the internal energy of a thermodynamic system is equal to the amount of heat energy added to the system minus the work done by the system on the surroundings.Please explain to me how this is related to the process of mutation and selection. Or the concept of metabolic cost. To me, this speaks about energy, and the ways it can be transformed into work and heat. What we're talking about is calorie restriction, and how it can play a role as a selection pressure. If you remove/lessen calorie restriction, what happens ? Remember, there are different solution for a given problem. We humans for example reproduce very poorly compared to lemmings. Does that mean we're less fit ? Seeing our actual progression, I doubt it.
This concept is very easy to understand. If fitness is a measure of a populations’ ability to reproduce and reproduction requires energy, any energy that a population has that can not be used for reproduction reduces the fitness of the population. That is what the “metabolic cost” is.
What ev demonstrates is the fundamental mathematics of mutation and selection. Dr Schneider has successful captured the essential effects of genome size, population, mutation rate and number of selection pressures in his model. I am not claiming evolution can’t happen, what I am claiming is that his model shows what the limitations of mutation and selection are. These limitations are demonstrated by the empirical data. If you study the mathematics of mutation and selection as demonstrated by Dr Schneider’s model, you will see what the effects of varying the different parameters in the model show. What his model shows is that short genome length, large populations with rapid reproduction times and high mutation rates evolve most rapidly. More importantly, the model shows that single selection pressures evolve far more rapidly than combination selection pressures. This is exactly what HIV shows. These mathematical and empirical facts show why it is impossible for large genome populations such as reptiles with slow reproductive rates and low mutation rates can not transform into birds. You don’t have the selection conditions and you don’t have sufficient mutation selection cycles.Blah, blah, blah... Please stop repeating always the same information. And relating to HIV, please explain to me why, if your model states that "evolution can stop" with only 3 selection pressures (which you somehow equate with the number of antivirals for HIV, feel free to correct me if I'm wrong there), HIV cannot be eradicated despite the more than 20 antivirals available to date. More than that, how it manages to develop resistance to HAART.
If you would study and understand the mathematics of ev and what the model show, this would be much more apparent to you. You have some homework to do in order to understand how mutation and selection actually works. Ev shows you that as you increase the genome length and the number of selection pressures, the evolutionary process becomes profoundly slow. If you run cases with ev using genome lengths comparable to HIV, you will see that three selection pressures can be adapted to but takes million of generations. If you use single selection pressures ev will evolve these conditions much more rapidly. This is analogous to monotherapy versus combination therapy with HIV. Monotherapy allows the virus to evolve to this single selection pressure far more rapidly than if three different selection pressures are applied simultaneously. Study the mathematics of mutation and selection and stop being a mathematically challenged evolutionarian.
If you want quantitative values from ev, it takes hundreds of millions of generations to evolve only 100 loci on a 100k genome. If you want empirical data, treating HIV with monotherapy the virus can evolve resistance to that drug in only a few weeks while three drug combination therapy can prevent evolution of resistant viruses for years, even decades. What is clear is that each additional selection pressure slows evolution further. Each additional selection pressure makes it more difficult for the population to traverse the fitness landscape to a new local optimum. This is how mutation and selection actually works.What happens when you increase the total weight of the selection pressures combined (whether with one or several selection pressures) ? Well, there is a definite drop in population. This is measured using quantitative PCR of viral charge for HIV. If there are less individuals, and the same mutation rate is conserved, then there are much less chances that the "winning combination" be achieved. Since using extra high doses of antiviral is harmfully toxic, we rely on their synergy to gain an advantage in toxicity.
Ev does allow to change the weights on the selection pressures but the model always allows 50% of the creatures to survive (there is no extinction in his model). It is clear that if a particular selection pressure requires multiple different mutations at multiple different loci it will be much more difficult for the population to evolve and if this pressure is intense on the population, it is much more likely to cause extinction. This feature is not included in ev. If you mathematically challenged evolutionarians would learn the mathematics of mutation and selection, you would include these types of features in your models so you could estimate what would be needed to cause the extinction of HIV. Instead you evolutionarians try to argue the multiple selection pressures accelerate evolution. You evolutionarians live in a brainwashed and biased fantasy world especially when it comes to how mutation and selection actually works.
It seems that some evolutionarians are getting tired of seeing your silly graph over and over again but we all know it is a fake.This is an interesting lie.

Who, exactly, do you claim shares your fantasy world?

If anyone agrees with kleinman that the data from my model is "fake", please feel free to speak out.
So let’s see Adequate’s silly graph again.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
In your evolutionarian fantasy world, multiple selection pressures accelerate evolution. Why don’t you post some fantasy citations? In the real world, there are an abundance of citations which show how mutation and selection actually works. I’ll post more examples below, imaginary superhero of amathematics.
Well, his grammar is relatively decent.
Tankyou quixote, an me twarn’t even a Inglish magor in kollige.
And he's a consummate, though somewhat repetitive, derider. Adept at deceit, too.
I’m only repetitive because you evolutionarians are such slow learners of how mutation and selection actually works. Deceit? Feel free to duplicate my results from ev, it shows how mutation and selection actually works. The 100+ citations of empirical evidence demonstrate the mathematical fact that ev shows, that multiple selection pressures slow the evolutionary process. I don’t need deceit to show how mathematically impossible the theory of evolution is.
You may have to explain what metabolic cost is to the readers of this thread, like joobz. He doesn’t understand that mutation and selection is a restatement of the first law of thermodynamic. Populations which can dedicate the most energy to reproduction are most fit.I completely forgot about the "Natural selection is a restatement..." nonsense.
So let’s see joobz description of chemistry and energy.
Envision a system of millions of forming and destructive chemical reactions. Now, envision that intermediates of there reactions associate through non-covalent means and that this complex becomes protected against the destructive reactive pathway, perhaps by a reversible precipitation. These new complexes result in a localized increased of new chemical species. These chemical species then progress in a new series of reaction... that is what I mean through cooperative means. I acknowledge this is complete speculation, but well within the range of chemical possibility. As long as there was enough free energy for these reaction to occur.
This joobz, you have an alchemist view of energy and chemistry. Let sunlight hit lead long enough and it will turn into gold.
There are some pretty sophisticated complications in these hypothetical multiple selection pressure scenarios. Remember that it's entirely possible the pressures could interfere in convoluted ways. The components of a system that add up to an adaptation that addresses all of the pressures might simultaneously each independently be worse for the organism under all of the selection pressures. It's also possible that multiple adaptations that address other selection pressures might combine under new selection pressures to form a totally new adaptation. All of the adaptations that eventually led to flight would be a very good example of this.

Just remember that this fitness landscape concept can be very counterintuitive sometimes. Be careful about assuming, because there's almost always an exception.
Delphi, I have posted over a hundred examples of how mutation and selection actually works, that is that multiple selection pressures profoundly slow the evolutionary process. Give us a single exception to all the examples that I have and will continue to present.
You should bear in mind that we're comparing simultaneous selection with cumulative sequential selection, i.e. at the end of the sequential process, exactly the same selection pressures obtain as are present throughout the simultaneous process. It might be that two mutations, each good in itself, interact to be lethal (the simplest case, I think, of what you're talking about) --- in which case a viable organism having both mutations can't be produced by either method.I was more trying to remind people to keep the real world context in mind. There's no one specific series of "correct" mutations in the natural world under either scenario. Basically, we're dealing with an optimization problem where the function being optimized is either changing over time or is static, but the final optima are the same.
Now you are addressing the real problem of mutation and selection, but talking about the real world with Adequate? Adequate is either faking or delusional when it comes to mutation and selection, his silly graph reveals this.
Cumulative sequential selection may present the population with a possible adaptation that works extremely well, but is terrible when another selection pressure is added. The population probably won't be able to adapt to the new pressure. It's stuck in an evolutionary dead end. If the population had been presented with all of the selection pressures from the beginning, it obviously would have taken a totally different evolutionary direction.
What does the data show? What happens to HIV when it is subjected to cumulative sequential selective pressures verses the same pressures simultaneously? Do you find different sets of mutations?
The opposite scenario is also possible. The sequential series selection pressures may allow the population to gradually adapt to an environment that would otherwise be inhospitable. It all depends on how the fitness landscape changes with the added selection pressures.
So Delphi, what are these sequential selection pressures that would allow a reptiles to metamorphose to birds?
The probability that a mutation will occur in a population depends on the contents of its genomes. If a beneficial mutation is requires a dramatic change from what has already evolved, it is unlikely to happen. If different adaptation for the selection pressure requires less dramatic changes, it's more likely the population will end up with the mutations for that adaptation.This is of course perfectly true, but I don't see what it has to do with the interaction of two adaptations to different selection pressures.
What this shows Adequate is that even though you have a PhD in mathematics, you know nothing about mutation and selection. If you ever had to solve a problem using an iterative technique, you would know that the more conditions you have to iterate on in order to solve the problem the slower the computation goes. This is analogous to what happens in mutation and selection. For a single selection condition, it is much easier to determine if the mutation is beneficial or detrimental. With multiple selection conditions, it becomes much more difficult to determine if the mutation is beneficial or not, especially if the mutation does not alter the fitness of the creature ability to reproduce by much. Unless the mutation gives a large benefit to the creature to reproduce, you are not going to see a rapid increase in the frequency of that mutation in the population. This markedly slows the populations’ ability to navigate the fitness landscape.

Delphi, are you really sure you want to examine the mathematics of mutation and selection realistically? Yours is the first coherent attempt at discussing this issue in a year of debate but prepare yourself for the wrath of your fellow evolutionarians if you continue this kind of talk.

Anyway, I continue to post real examples of how mutation and selection actually works. Again, this is an example from the field of oncology and I dedicate this citation to Dr Schneider and the cohort at the National Cancer Institute. Adequate, you can read the citation as well and be confused.
http://clincancerres.aacrjournals.org/cgi/content/full/10/16/5299?ck=nck (http://clincancerres.aacrjournals.org/cgi/content/full/10/16/5299?ck=nck)
Current limitations of chemotherapy and radiation therapy are their inability to effectively treat metastatic disease. As with other modalities of treatment, oncolytic virotherapy, by itself, has not been effective in complete tumor eradication in both preclinical animal models and clinical studies. It appears that the best chance for complete tumor eradication lies with combining its mechanism of action with current treatment strategies of chemo- and radiation therapies and the emerging field of clinical gene therapy. The theory, based on combination chemotherapy, is that attacking tumor cells through different mechanisms of action will prevent tumor cells from having time to develop resistance to treatment.
This is how mutation and selection works. Combination selection pressures slow the evolution of resistant cancer cells to treatment.

[Belz...]

...the numerous citations of real examples of mutation and selection conflict so completely with your evolutionarian belief system that you have gone into denial of what these empirical examples of mutation and selection are showing

Begging the question. I have no belief. Try again.

Meanwhile, I'm still waiting for proof. Not lies, mind you. Proof.

but in time, you will come to understand how mutation and selection actually works.

Not with your gibberish I won't.

The phenomenon of mutation and selection is far too important in multiple areas of medicine and science to let you evolutionarians put your strange and bizarre interpretations which block scientific and medical advancement.

Evolution by mutation and selection is probably the best-supported scientific theory out there. So if that's not science, nothing else is. Let's go back to witch doctors and inquisitors, shall we ?

[kleinman]

...the numerous citations of real examples of mutation and selection conflict so completely with your evolutionarian belief system that you have gone into denial of what these empirical examples of mutation and selection are showingBegging the question. I have no belief. Try again.

Meanwhile, I'm still waiting for proof. Not lies, mind you. Proof.
Belz, you are way behind on the learning curve when it comes to the topic of the mathematics of mutation and selection. Much of the mathematical behavior of ev was discussed earlier in this thread with the results of hundreds of cases from this computer simulation posted either on this thread or the corresponding thread on the Evolutionisdead forum. Have you tried reading Dr Schneider’s work on the ev model yet? If you want me to discuss the basics of the ev computer model, where do you want me to start?
but in time, you will come to understand how mutation and selection actually works.Not with your gibberish I won't.
You are mistaken, you do not understand the mathematics of mutation and selection, that’s why you think what I am saying is gibberish. When you have evolutionarians like Adequate posting silly graphs which say that multiple simultaneous selection pressure accelerate evolution and Paul trying to make convoluted explanations to squirm out of what Dr Schneider’s model shows, it is easy to see why you would be so confused by how mutation and selection actually works. However, if you want, we can start again and post and explain the results of the ev model. Then you might be able to learn how mutation and selection actually works and the empirical results I have been posting will make sense to you (that is, if you don’t go into denial).
The phenomenon of mutation and selection is far too important in multiple areas of medicine and science to let you evolutionarians put your strange and bizarre interpretations which block scientific and medical advancement.Evolution by mutation and selection is probably the best-supported scientific theory out there. So if that's not science, nothing else is. Let's go back to witch doctors and inquisitors, shall we ?
Don’t mistake the large volume of mythology that has been written about the theory of evolution in the past 150 years with science. Dr Schneider’s mathematical model of random point mutations and natural selection has only been around for a little over 20 years and the data which demonstrates this mathematics the mathematics of mutation and selection has only been observed for about 50 years. The amount of data that demonstrates how mutation and selection actually works has exploded in the past 20 years with the appearance of HIV and a wide variety of viral, bacterial infections and parasitic. You evolutionarians need to come up to date with the mathematics and empirical data that are now available which describe how mutation and selection actually works. What that mathematics and empirical data show is that multiple simultaneous selection pressures profoundly slow a populations’ ability to adapt to these selection pressures. The science fiction of the theory of evolution is meeting with the mathematics and empirical data of how mutation and selection actually works and it shows that the theory of evolution is mathematically impossible.

[Dr Adequate]

So, you mathematically challenged evolutionarians are still unable to shed much light on how mutation and selection actually works. Well, let’s see if we can help illuminate you and your bizarre interpretation of the mathematical and empirical facts of how this phenomenon actually works.

Now pussycat, the author of the program, Dr Tom Schneider of the National Cancer Institute purports that his model simulates the important essentials of the mutation and selection process and I agree with the author. The peer reviewer at the Oxford University Press Journal Nucleic Acids Research agreed enough with Dr Schneider to publish the results of his model and have now posted more than 100 citations which confirms the results from his model. I know this entirely contradicts your evolutionarian belief system and denial is the only way for you evolutionarians to deal with these mathematical and empirical facts but sorry pussycat, facts are facts. Since you don’t want to discuss the mathematics or empirical facts of mutation and selection, perhaps you would like to talk about the lies your parents told you.

Taffer, you can’t tell the difference between mutation and selection and recombination and selection. Both are sorting problems. Mutation and selection is the sorting of beneficial and detrimental mutations while recombination and selection is the sorting of beneficial and detrimental alleles. One of the reason sorting of mutation and selection becomes so profoundly slow is the 4^G search space while recombination and selection has a much smaller search space because of the much, much smaller number of alleles that are being sorting. In addition, mating is often not random in the recombination and selection process giving even much more rapid morphological changes in the population. Dog breeding demonstrates this phenomenon. If you don’t like this example because of human involvement in the selection process, take Darwin’s own example of the variations of finch beaks which also demonstrates this phenomenon. Since you are having a hard time understanding the difference between mutation and selection and recombination and selection, here is a citation from a professor at Rice University.
http://www.rice.edu/sallyport/2007/winter/features/evolution.html (http://www.rice.edu/sallyport/2007/winter/features/evolution.html)

Professor Silberg understands how slow the sorting process for mutation and selection is and if a population needs to respond rapidly to a selection pressure, recombination is much more rapid.

Taffer, you also don’t understand that recombination without error can not create new information (alleles) in the gene pool and that recombination with natural selection can cause the loss of information (alleles) from the gene pool. Recombination with natural selection can not transform reptiles into birds. You need mutation and natural selection to make this metamorphosis. However, mutation and natural selection is profoundly slow if you have combination selection pressures, especially if you have small populations with slow reproductive times.

Why cyborg, what I don’t know would fill far more than 129 pages, but what I do know about mutation and selection will fill such a thread. In all fairness, if we removed the evolutionarian cruft, this thread would be much shorter.

Belz, I know you are confused by Dr Schneider’s mathematical model of mutation and selection and the numerous citations of real examples of mutation and selection conflict so completely with your evolutionarian belief system that you have gone into denial of what these empirical examples of mutation and selection are showing but in time, you will come to understand how mutation and selection actually works. I will continue to post more empirical examples of how mutation and selection actually works while we can wait for an eternity for a single example from you evolutionarians of multiple selection pressures accelerating evolution. The phenomenon of mutation and selection is far too important in multiple areas of medicine and science to let you evolutionarians put your strange and bizarre interpretations which block scientific and medical advancement.

You evolutionarians are looking for any way you can to deny the mathematical and empirical facts of how mutation and selection actually works. Do you think you can decide that if I am insincere that the mathematical and empirical facts of mutation and selection are no longer valid? I keep telling you; one of the four cardinal symptoms of evolutionism is denialophilia.

Certainly I understand that you can have mutations anywhere in the genome that might lead to a match with the weight matrix. However, if I understand your selection condition for locating binding sites only count as mistakes when a binding site is not identified where one should occur. Any weight matrix matches which might occur outside the binding sites when using only the binding site location selection condition it being applied will not affect selection of creatures. There is no reason to believe that the entire genome will evolve to binding sites.

Paul, the only function for selection is to evolve sequences of bases that improve the fitness of the population to reproduce. Are you going to propose that Dr Schneider’s model evolves real sequences of bases that will produce transcribed proteins that will bind to these sequences in reality?

Paul, I know exactly what the point at hand is. That point is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process. Your own computer simulation shows this and the empirical data shows this. You are working very hard to squirm out of this mathematical and empirical fact but it isn’t going to happen. Your only choice is to go into denial of this mathematical and empirical fact. Your evolutionarian belief system impairs your ability to understand these mathematical and empirical facts.

Paul, there is no Rcapacity problem; the only problem you evolutionarians have is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process. Your own computer model shows this and the empirical data shows this. What I contend about ev is that it is an idealize model of random point mutation and natural selection that properly captures the mathematical behavior of the effects of genome length, population, number of selection pressures and several other parameters of the mutation and selection process. Ev does not simulate the evolution of real binding sites.

Paul, do you believe the ev is evolving real binding sites?

This concept is very easy to understand. If fitness is a measure of a populations’ ability to reproduce and reproduction requires energy, any energy that a population has that can not be used for reproduction reduces the fitness of the population. That is what the “metabolic cost” is.

If you would study and understand the mathematics of ev and what the model show, this would be much more apparent to you. You have some homework to do in order to understand how mutation and selection actually works. Ev shows you that as you increase the genome length and the number of selection pressures, the evolutionary process becomes profoundly slow. If you run cases with ev using genome lengths comparable to HIV, you will see that three selection pressures can be adapted to but takes million of generations. If you use single selection pressures ev will evolve these conditions much more rapidly. This is analogous to monotherapy versus combination therapy with HIV. Monotherapy allows the virus to evolve to this single selection pressure far more rapidly than if three different selection pressures are applied simultaneously. Study the mathematics of mutation and selection and stop being a mathematically challenged evolutionarian.

Ev does allow to change the weights on the selection pressures but the model always allows 50% of the creatures to survive (there is no extinction in his model). It is clear that if a particular selection pressure requires multiple different mutations at multiple different loci it will be much more difficult for the population to evolve and if this pressure is intense on the population, it is much more likely to cause extinction. This feature is not included in ev. If you mathematically challenged evolutionarians would learn the mathematics of mutation and selection, you would include these types of features in your models so you could estimate what would be needed to cause the extinction of HIV. Instead you evolutionarians try to argue the multiple selection pressures accelerate evolution. You evolutionarians live in a brainwashed and biased fantasy world especially when it comes to how mutation and selection actually works.

So let’s see Adequate’s silly graph again.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

In your evolutionarian fantasy world, multiple selection pressures accelerate evolution. Why don’t you post some fantasy citations? In the real world, there are an abundance of citations which show how mutation and selection actually works. I’ll post more examples below, imaginary superhero of amathematics.

Tankyou quixote, an me twarn’t even a Inglish magor in kollige.

I’m only repetitive because you evolutionarians are such slow learners of how mutation and selection actually works. Deceit? Feel free to duplicate my results from ev, it shows how mutation and selection actually works. The 100+ citations of empirical evidence demonstrate the mathematical fact that ev shows, that multiple selection pressures slow the evolutionary process. I don’t need deceit to show how mathematically impossible the theory of evolution is.

So let’s see joobz description of chemistry and energy.

This joobz, you have an alchemist view of energy and chemistry. Let sunlight hit lead long enough and it will turn into gold.

Delphi, I have posted over a hundred examples of how mutation and selection actually works, that is that multiple selection pressures profoundly slow the evolutionary process. Give us a single exception to all the examples that I have and will continue to present.

Now you are addressing the real problem of mutation and selection, but talking about the real world with Adequate? Adequate is either faking or delusional when it comes to mutation and selection, his silly graph reveals this.

What does the data show? What happens to HIV when it is subjected to cumulative sequential selective pressures verses the same pressures simultaneously? Do you find different sets of mutations?

So Delphi, what are these sequential selection pressures that would allow a reptiles to metamorphose to birds?

What this shows Adequate is that even though you have a PhD in mathematics, you know nothing about mutation and selection. If you ever had to solve a problem using an iterative technique, you would know that the more conditions you have to iterate on in order to solve the problem the slower the computation goes. This is analogous to what happens in mutation and selection. For a single selection condition, it is much easier to determine if the mutation is beneficial or detrimental. With multiple selection conditions, it becomes much more difficult to determine if the mutation is beneficial or not, especially if the mutation does not alter the fitness of the creature ability to reproduce by much. Unless the mutation gives a large benefit to the creature to reproduce, you are not going to see a rapid increase in the frequency of that mutation in the population. This markedly slows the populations’ ability to navigate the fitness landscape.

Delphi, are you really sure you want to examine the mathematics of mutation and selection realistically? Yours is the first coherent attempt at discussing this issue in a year of debate but prepare yourself for the wrath of your fellow evolutionarians if you continue this kind of talk.

Anyway, I continue to post real examples of how mutation and selection actually works. Again, this is an example from the field of oncology and I dedicate this citation to Dr Schneider and the cohort at the National Cancer Institute. Adequate, you can read the citation as well and be confused.
http://clincancerres.aacrjournals.org/cgi/content/full/10/16/5299?ck=nck (http://clincancerres.aacrjournals.org/cgi/content/full/10/16/5299?ck=nck)

This is how mutation and selection works. Combination selection pressures slow the evolution of resistant cancer cells to treatment. I suppose the only new lie here as such is your pretense that I have never "had to solve a problem using an iterative technique" --- a laughably clownish lie, since everyone reading this thread can see code written by me which does just that.

Apart from that, you've just posted the same unevidenced, unmathematical, vacuous bullcrap over again to an audience who weren't deceived by your childish lies the first hundred times you told them.

[Dr Adequate]

Belz, you are way behind on the learning curve when it comes to the topic of the mathematics of mutation and selection. Much of the mathematical behavior of ev was discussed earlier in this thread with the results of hundreds of cases from this computer simulation posted either on this thread or the corresponding thread on the Evolutionisdead forum. Have you tried reading Dr Schneider’s work on the ev model yet? If you want me to discuss the basics of the ev computer model, where do you want me to start?

You are mistaken, you do not understand the mathematics of mutation and selection, that’s why you think what I am saying is gibberish. When you have evolutionarians like Adequate posting silly graphs which say that multiple simultaneous selection pressure accelerate evolution and Paul trying to make convoluted explanations to squirm out of what Dr Schneider’s model shows, it is easy to see why you would be so confused by how mutation and selection actually works. However, if you want, we can start again and post and explain the results of the ev model. Then you might be able to learn how mutation and selection actually works and the empirical results I have been posting will make sense to you (that is, if you don’t go into denial).

Don’t mistake the large volume of mythology that has been written about the theory of evolution in the past 150 years with science. Dr Schneider’s mathematical model of random point mutations and natural selection has only been around for a little over 20 years and the data which demonstrates this mathematics the mathematics of mutation and selection has only been observed for about 50 years. The amount of data that demonstrates how mutation and selection actually works has exploded in the past 20 years with the appearance of HIV and a wide variety of viral, bacterial infections and parasitic. You evolutionarians need to come up to date with the mathematics and empirical data that are now available which describe how mutation and selection actually works. What that mathematics and empirical data show is that multiple simultaneous selection pressures profoundly slow a populations’ ability to adapt to these selection pressures. The science fiction of the theory of evolution is meeting with the mathematics and empirical data of how mutation and selection actually works and it shows that the theory of evolution is mathematically impossible. So, you're just reciting the same old crap, then?

[Dr Adequate]

By why would a mutation beneficial for future selections but with no effect on current pressures be completely lost from the population? Genetic drift. The chances of a new neutral mutation achieving fixation are 1/fNe, where f is the ploidy of the organisms and Ne is the effective population. Now, this is a good approximation to 0 when Ne is large. And a mutation which does not achieve fixation will ulimately go extinct (except in cases of genetic equilibrium).

As I said, I was looking at an idealised case (it corresponds best to a huge population and a huge selective advantage) in order to make the underlying facts about probability theory clear.

Of course, I'm just a mathematically challenged evolutionist mathematician who doesn't understand has studied the mathematics of mutation and selection, which is why I could explain that to you and kleinman couldn't.

[kleinman]

I suppose the only new lie here as such is your pretense that I have never "had to solve a problem using an iterative technique" --- a laughably clownish lie, since everyone reading this thread can see code written by me which does just that.

Apart from that, you've just posted the same unevidenced, unmathematical, vacuous bullcrap over again to an audience who weren't deceived by your childish lies the first hundred times you told them.
If you want to talk about childish lies, let’s see yours:
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Your graph is a fake and you are a fake Adequate. You have no examples of your silly graph. You evolutionarians have been deceived for 150 years. Here is how mutation and selection actually works.

http://www.sciencemag.org/cgi/content/abstract/253/5027/1557 (http://www.sciencemag.org/cgi/content/abstract/253/5027/1557)
Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.

http://gateway.nlm.nih.gov/MeetingAbstracts/102246574.html (http://gateway.nlm.nih.gov/MeetingAbstracts/102246574.html)
BACKGROUND: DAPD, (-)-beta -D-2, 6-diaminopurine dioxolane, is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against HIV-1 and Hepatitis B virus. DAPD is deaminated in vivo by adenosine deaminase to give (-)-beta -D-dioxolane guanine (DXG) which has potent activity against HIV-1 in vitro. EC[50] values determined for DXG in PBMCs against several wild type isolates of HIV-1 ranged from 30 nM to 290 nM. The 50% cytotoxic dose, CC[50], for both DAPD and DXG is greater than 500 micro- M. Toxicology studies of 1 month duration were conducted in mice, rats, and two species of monkeys at doses up to 1200 mg/kg/day with no significant dose-limiting toxicity observed.

RESULTS: Passage of HIV-1 in the presence of increasing concentrations of DXG resulted in selection of virus containing an L74V mutation (4-fold increase in EC[50]) in our laboratory. Others have described the selection of a K65R mutation (8-fold increase in EC[50], Mellors, et. al., 1996) by in vitro passage in DXG. Recombinant viruses and clinical isolates of HIV-1 with mutations at codons 41L, 67N, 69D, 70R, 103N, 184V, 190A, 215Y, and 219Q, alone or in combination, from patients who have failed NRTI and/or NNRTI combination therapies remain sensitive to DXG. Viruses with mutations associated with multi-NRTI resistance due to SS or SG insertions between codons 68/69 were sensitive to DXG. A virus containing S68G, Q151M, and T215Y was sensitive to DXG, but viruses with multiple mutations that included K65R, F116Y, and Q151M demonstrated a 40- to 54-fold increase in EC[50] for DXG.

CONCLUSIONS: Based upon the antiviral activity observed in vitro and the favorable toxicology profile observed to date, a phase I/II dose escalation study has been initiated in HIV-infected patients. DAPD is a promising new NRTI that may be useful in combination therapies for HIV-infected patients who are antiviral therapy naive or experienced, including patients infected with drug-resistant strains of HIV.
Adequate, you are incompetent in the mathematics of mutation and selection. You have no empirical evidence for your silly graph which you contend that multiple selection pressures accelerate evolution while I continue to post example after example of multiple selection pressures slowing evolution. This is exactly what the peer reviewed and published computer simulation ev shows. The only thing correct about your post is that you are an imaginary superhero. I do enjoy annoying you with the mathematical and empirical facts of how mutation and selection actually works.

[Paul C. Anagnostopoulos]

Certainly I understand that you can have mutations anywhere in the genome that might lead to a match with the weight matrix. However, if I understand your selection condition for locating binding sites only count as mistakes when a binding site is not identified where one should occur. Any weight matrix matches which might occur outside the binding sites when using only the binding site location selection condition it being applied will not affect selection of creatures. There is no reason to believe that the entire genome will evolve to binding sites.
There is plenty of reason to believe it: Try it. If you run the standard model with no spurious binding mistakes, you'll see that almost every position is bound.

But what I was correcting was your statement "Setting the spurious binding site selection conditions to zero does not mean that every locus in the genome represents a binding site." Of course not, since the binding sites are at specific positions on the genome. The important point is that you are not evolving the same function with only one selection condition turned on.


Paul, the only function for selection is to evolve sequences of bases that improve the fitness of the population to reproduce. Are you going to propose that Dr Schneider’s model evolves real sequences of bases that will produce transcribed proteins that will bind to these sequences in reality?
This is such an absurd question that I must assume that I misunderstand it.


Paul, I know exactly what the point at hand is. That point is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process.
Compared to applying only one selection pressure? In that case, you are not evolving the same function. Compared to applying all the pressures sequentially and cumulatively? We have not performed that experiment.


Paul, there is no Rcapacity problem; the only problem you evolutionarians have is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process.
As I've said before, you are denying that the width of the binding site must be sufficient to allow a unique code in those positions. Perhaps you could explain, then, how it is that the transcription factor distinguishes binding sites from all other positions on the genome?


Paul, do you believe the ev is evolving real binding sites?
Are you asking whether Ev is a biological organism?

~~ Paul

[Dr Adequate]

If you want to talk about childish lies, let’s see yours: Go right ahead, if you can think of any.

http://img514.imageshack.us/img514/3974/genegraphhx4.jpg

http://forums.randi.org/images/smilies/doglaugh.gif

Your graph is a fake and you are a fake Adequate. You have no examples of your silly graph. You evolutionarians have been deceived for 150 years. Here is how mutation and selection actually works.

http://www.sciencemag.org/cgi/content/abstract/253/5027/1557 (http://www.sciencemag.org/cgi/content/abstract/253/5027/1557)


http://gateway.nlm.nih.gov/MeetingAbstracts/102246574.html (http://gateway.nlm.nih.gov/MeetingAbstracts/102246574.html)

Adequate, you are incompetent in the mathematics of mutation and selection. You have no empirical evidence for your silly graph which you contend that multiple selection pressures accelerate evolution while I continue to post example after example of multiple selection pressures slowing evolution. This is exactly what the peer reviewed and published computer simulation ev shows. The only thing correct about your post is that you are an imaginary superhero. I do enjoy annoying you with the mathematical and empirical facts of how mutation and selection actually works. Oh, you couldn't think of any.

You know, if you're going to call someone a liar, it makes you look better if you can at least prove him wrong about something.

[Dr Adequate]

Watch, I'll show you how.

Now pussycat, the author of the program, Dr Tom Schneider of the National Cancer Institute purports that his model simulates the important essentials of the mutation and selection process and I agree with the author Now, first I show that your statement about Dr Schneider is false.

[L]arge environmentally diverse worldwide populations, sexual recombination and interspecies genetic transfer ... are undoubtedly important in accounting for human evolution.* (http://www.ccrnp.ncifcrf.gov/~toms/paper/ev/latex/node5.html) However it would still be possible that you were merely mistaken. To prove that you are a liar, I must also demonstrate that you are well aware of what Dr Schneider actually thinks.

This is easy to do, since you quoted that very same passage from Dr Schneider yourself, here (http://forums.randi.org/showthread.php?page=7&t=67385).

Now you have a go.

Oh, wait, I haven't told any lies, have I?

[Dr Adequate]

If you ever had to solve a problem using an iterative technique, you would know that the more conditions you have to iterate on in order to solve the problem the slower the computation goes. Read my little parable again. Concentrate on the "NOTE FOR COMPLETE MORONS, I.E. KLEINMAN", until you understand how frickin' stupid you're being.

Let's see if we can explain it in language that kleinman would understand. Suppose a stupid lunatic thinks he hears a magic sky fairy telling him to gather two of every kind of animal.

Because he's a halfwit, he goes wandering around at random looking for the animals.

Now, consider the following two options:

(1) He collects the animals he stumbles across in strict alphabetical order, starting with aardvarks and working his way along the list. If he happens to see an animal, and it's not the next one on his list, he ignores it.

(2) When he sees an animal, if he hasn't already got a pair, he collects it.

Which method do you think would be faster?

NOTE FOR COMPLETE MORONS, I.E. KLEINMAN: the fact that both methods take longer the more animals there are on the list does not somehow magically mean that the first method is better.

[delphi_ote]

*sigh* Who let the little kid sit at the grown ups table?

[kleinman]

Certainly I understand that you can have mutations anywhere in the genome that might lead to a match with the weight matrix. However, if I understand your selection condition for locating binding sites only count as mistakes when a binding site is not identified where one should occur. Any weight matrix matches which might occur outside the binding sites when using only the binding site location selection condition it being applied will not affect selection of creatures. There is no reason to believe that the entire genome will evolve to binding sites.There is plenty of reason to believe it: Try it. If you run the standard model with no spurious binding mistakes, you'll see that almost every position is bound.

But what I was correcting was your statement "Setting the spurious binding site selection conditions to zero does not mean that every locus in the genome represents a binding site." Of course not, since the binding sites are at specific positions on the genome. The important point is that you are not evolving the same function with only one selection condition turned on.
Running the model with no spurious binding mistakes gives almost every position bound not because they are being selected this way, it is because the threshold for the weight matrix is so low that it is very easy for the model to find matches. That’s why it takes only one generation to eliminate missed binding sites if that is the only selection condition imposed. Are you going to try to contend that selection is occurring in the nonbinding site region when the only selection condition is missed binding sites?

You keep trying to impose the condition of function on the mutation and selection process. The only function of selection is to improve the fitness of the population to reproduce. The ev model does not evolve realistic sequences of functioning genes whether you are using a single selection condition or all three selection conditions simultaneously. If you think there is another goal for the selection process than the improvement of the populations’ fitness to reproduce, then why did you post this on another thread?
I think TalkOrigins is the place to go. No need to rewrite all their marvelous articles.

However, I also think a 1- or 2-page succinct summary of the main evolution debate points would be a great idea. For example, a paragraph titled "Evolution is not goal-directed" could then explain, in simple terms, exactly what that means.
Fitness to reproduce is the goal for the selection process, not some particular function.
Paul, the only function for selection is to evolve sequences of bases that improve the fitness of the population to reproduce. Are you going to propose that Dr Schneider’s model evolves real sequences of bases that will produce transcribed proteins that will bind to these sequences in reality?This is such an absurd question that I must assume that I misunderstand it.
You are the one saying that selection in ev must give a particular function. All ev does is try to give sequences of bases which satisfy the selection conditions, that’s the only function of these sequences of bases.
Paul, I know exactly what the point at hand is. That point is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process.Compared to applying only one selection pressure? In that case, you are not evolving the same function. Compared to applying all the pressures sequentially and cumulatively? We have not performed that experiment.
Would you expect a protease inhibitor to select for mutations in a reverse transcriptase inhibitor? What you are trying to do is link the selection pressures in ev which is an artificial linkage you are trying to make. If you have a single selection condition in the model which eliminates spurious binding in the nonbinding site region of the genome, the elimination of mistakes gives sequences of bases that don’t match the weight matrix, if you use all three selection conditions, convergence of the program still gives the same final condition in the nonbinding site region, that is no sequences of bases in the nonbinding site region that give a match to the weight matrix. That is the only function of the selection condition which eliminates spurious binding in the nonbinding site region of the genome. I look forward to you performing the experiment of applying the selection pressures sequentially and cumulatively, there’s your big opportunity to prove my hypothesis wrong. Of course we have the massive amount of empirical evidence which shows that sequential and cumulative selection pressures evolve much more rapidly than when the pressures are applied simultaneously.
Paul, there is no Rcapacity problem; the only problem you evolutionarians have is that multiple selection pressures when applied simultaneously profoundly slows the evolutionary process.As I've said before, you are denying that the width of the binding site must be sufficient to allow a unique code in those positions. Perhaps you could explain, then, how it is that the transcription factor distinguishes binding sites from all other positions on the genome?
The explanation for that is that with a wider binding site (and a wider weight matrix) you have fewer errors in the nonbinding site region for the same G. The only thing that changes in the model as you lengthen G is the number of spurious bindings you get in the nonbinding site region, the wider binding site reduces this number allowing you to converge larger genomes. If you want to call that the Rcapacity effect, comfort yourself with that thought. Regardless of the length of G, you can always evolve each of the selection conditions individually even when you can’t evolve the conditions simultaneously. That is the point. Single selection conditions evolve much more rapidly than combined selection conditions.
Paul, do you believe the ev is evolving real binding sites?Are you asking whether Ev is a biological organism?
Of course not, you know full well that ev is not a biological organism and it is not evolving real binding sites. Ev only evolves sequences of bases that satisfy the selection conditions imposed and ev evolves these conditions far more rapidly when applied individually than when applied simultaneously. That is what you have gone into denial about what the ev model shows and that is why it would take years of cpu time to do an e coli size genome if you try to evolve all three selection conditions simultaneously. It also happens to be the way real biological populations evolve. Paul, perhaps you want to embrace Adequate’s silly graph. He seems to think it represents reality. Here’s what he says:
If you want to talk about childish lies, let’s see yours:Go right ahead, if you can think of any.
Here is your fake graph and your fake claim.
http://img514.imageshack.us/img514/3974/genegraphhx4.jpg
The red line shows generations to achieve fixation of n alleles acted on by n selection pressures, the n+1th selection pressure being introduced only after the nth allele is fixed.

The blue line shows generations to achieve fixation of n alleles acted on by n selection pressures simultaneously.

All other features and parameters of the two models are identical. The model is designed so that the relative advantage of n+1 new genes over n (when selection is acting) is the same for all n, i.e. each new allele carries the same advantage.

Note how with simultaneous selection pressures the rate of evolution (fixations/generation) increases with the number of selection pressures.
http://forums.randi.org/images/smilies/doglaugh.gif
Could you give us a real example of your silly gif which shows that multiple selection pressures accelerate evolution cheese wiz?
Here’s another example how mutation and selection actually works.

http://www.natap.org/2007/EASL/EASL_44.htm (http://www.natap.org/2007/EASL/EASL_44.htm)
"....These data suggest the genetic barrier to resistance in patients upon clinical dosing may be high with ITMN-191....." note from Jules: there are 17 substantive new HCV drugs in pre-clinical and clinical development (in patients). We are at the beginning of trying to understand drug resistance. Drug resistance will be an issue, but it is likely to be different than in HIV...will we be able to sequence protease inhibitors, perhaps...but we don't know yet. Will we be able to eliminate peginterferon... perhaps never, we don't know but it will take 6 years to find out... will we be able to eliminate ribavirin... we don't know and this should take at least 2 years or more to find out...clearly, combination therapy with oral HCV drugs is the therapeutic regimen for the future, which for at least a number of years will contain also peginterferon plus likely also ribavirin.
Adequate, your fake graph is representative of the false theory of evolution from the past, the present and the future shows that multiple selection pressures slow evolution. You have no real examples of your silly graph; you and your graph are fakes.

[Paul C. Anagnostopoulos]

Running the model with no spurious binding mistakes gives almost every position bound not because they are being selected this way, it is because the threshold for the weight matrix is so low that it is very easy for the model to find matches. That’s why it takes only one generation to eliminate missed binding sites if that is the only selection condition imposed. Are you going to try to contend that selection is occurring in the nonbinding site region when the only selection condition is missed binding sites?
What do you mean by "not because they are being selected this way"?

When there is only one selection pressure---for the predetermined binding sites to bind the transcription factor---then the tendency is for the genome to evolve so that every position binds the factor. That's it, period. This occurs "faster" than the standard model because there is no selectivity in the binding process.


You keep trying to impose the condition of function on the mutation and selection process. The only function of selection is to improve the fitness of the population to reproduce. The ev model does not evolve realistic sequences of functioning genes whether you are using a single selection condition or all three selection conditions simultaneously. If you think there is another goal for the selection process than the improvement of the populations’ fitness to reproduce, then why did you post this on another thread?
I'm not imposing any stupid function on the mutation and selection process. I'm talking about the function of the evolved mechanism. Evolved mechanisms do perform functions, don't you agree? If you are going to compare different evolved mechanisms and then talk about the "speed" of evolution, which is precisely what you are doing, you are going to reach silly conclusions.


You are the one saying that selection in ev must give a particular function. All ev does is try to give sequences of bases which satisfy the selection conditions, that’s the only function of these sequences of bases.
I agree. But you still can't compare the "speeds" of evolution when evolving sequences that satisfy different combinations of selection conditions.


The explanation for that is that with a wider binding site (and a wider weight matrix) you have fewer errors in the nonbinding site region for the same G.
This is a statement of a fact. Why does a wider binding site do a better job and is there is discontinuity in the performance of different widths?


Of course not, you know full well that ev is not a biological organism and it is not evolving real binding sites.
Then what did you mean by the word real in the question " Paul, do you believe the ev is evolving real binding sites?"


Ev only evolves sequences of bases that satisfy the selection conditions imposed and ev evolves these conditions far more rapidly when applied individually than when applied simultaneously.
I agree. However, the rapidity or slowness is uninteresting if you are not talking about evolving the same functional result of selection conditions.

~~ Paul

[kleinman]

Running the model with no spurious binding mistakes gives almost every position bound not because they are being selected this way, it is because the threshold for the weight matrix is so low that it is very easy for the model to find matches. That’s why it takes only one generation to eliminate missed binding sites if that is the only selection condition imposed. Are you going to try to contend that selection is occurring in the nonbinding site region when the only selection condition is missed binding sites?What do you mean by "not because they are being selected this way"?
Try these cases, all have G=32768, all other parameters baseline except the weight factors for each case is set to 0 except the single selection pressure being applied is set to 1. Examine the best and worst cases after only one generation.

Binding site weight = 1
-------Best case/Worse case
Mistakes 0/1
Spurious Binding within gene = 1
-------Best case/Worse case
Mistakes 6/121
Spurious Binding outside gene = 1
-------Best case/Worse case
Mistakes 2434/31428

In particular, consider the worst case from spurious binding outside the gene. You have 31,428 located spurious binding sites for each locus on one of the creatures after only a single generation. Your weight matrix is threshold for identifying matches is very low. Many combinations of bases will give a match to the weight matrix.
When there is only one selection pressure---for the predetermined binding sites to bind the transcription factor---then the tendency is for the genome to evolve so that every position binds the factor. That's it, period. This occurs "faster" than the standard model because there is no selectivity in the binding process.
Random sequences easily match the weight matrix even before the mutation selection process has started. In fact, 1 of the 64 creature starts with 31,428 spurious binding sites.
You keep trying to impose the condition of function on the mutation and selection process. The only function of selection is to improve the fitness of the population to reproduce. The ev model does not evolve realistic sequences of functioning genes whether you are using a single selection condition or all three selection conditions simultaneously. If you think there is another goal for the selection process than the improvement of the populations’ fitness to reproduce, then why did you post this on another thread?I'm not imposing any stupid function on the mutation and selection process. I'm talking about the function of the evolved mechanism. Evolved mechanisms do perform functions, don't you agree? If you are going to compare different evolved mechanisms and then talk about the "speed" of evolution, which is precisely what you are doing, you are going to reach silly conclusions.
Sure you are imposing function to the mutation and selection process beyond increased fitness to reproduce for the population. Each of the selection condition requirements are only that the number of mistakes be minimized, it is you who want to impost some type of special functional condition beyond that. The function of evolved mechanism is to improve the reproductive fitness of the population. Are you trying to say there is a goal for evolution?
You are the one saying that selection in ev must give a particular function. All ev does is try to give sequences of bases which satisfy the selection conditions, that’s the only function of these sequences of bases.I agree. But you still can't compare the "speeds" of evolution when evolving sequences that satisfy different combinations of selection conditions.
Certainly I can make that kind of comparison because that is how it works in reality. Ev has three selection conditions that the model tries to minimize the number of errors for these conditions. It is an optimization problem with three optimization conditions. If you run the model and try to optimize all three conditions simultaneously, the model runs very slowly for all but the shortest genomes. If you run the model with only a single selection condition, the model can optimize the single condition very easily, even for larger genome cases. Mutation and selection is simply an optimization problem.
The explanation for that is that with a wider binding site (and a wider weight matrix) you have fewer errors in the nonbinding site region for the same G.This is a statement of a fact. Why does a wider binding site do a better job and is there is discontinuity in the performance of different widths?
Try these cases, all have G=32768, binding site width=12, weight width=11, all other parameters baseline except the weight factors for each case is set to 0 except the single selection pressure being applied is set to 1. Examine the best and worst cases after only one generation.

Binding site weight = 1
-------Best case/Worse case
Mistakes 2/16
Spurious Binding within gene = 1
-------Best case/Worse case
Mistakes 5/462
Spurious Binding outside gene = 1
-------Best case/Worse case
Mistakes 399/27143

Simply increasing the binding site width reduces the number of spurious bindings outside the gene by thousand after only a single generation.

What makes you think there is a discontinuity in the generations for convergence/genome length curve? Exponential curves behave like this. Consider the following data using baseline values, mutation rate=1/G, you get the following data:
Genome Length/Generations for convergence
256/675
512/2925
1024/10108
2048/35,486
4096/162,892
8192/710,152
16384/6,894,433
Do you think the G=32k case will not converge or are we simply on the steep portion of the exponential curve?
Of course not, you know full well that ev is not a biological organism and it is not evolving real binding sites.Then what did you mean by the word real in the question " Paul, do you believe the ev is evolving real binding sites?"
What I meant by the word “real” is actual functioning binding sites. The only thing that ev evolves is sequences of bases which satisfy the selection condition, there is nothing real being evolved in Dr Schneider’s model. What Dr Schneider’s model demonstrates is the mathematics of the optimization of his selection conditions. It is this mathematical behavior which is reflected in the real cases of mutation and selection. It demonstrates what happens when you have multiple selection conditions applied simultaneously and how profoundly slow this process is. Try defining 3 different weight matrices that are applied to three different portions of the genome and you will still have difficulty evolving the three selection conditions simultaneously.
Ev only evolves sequences of bases that satisfy the selection conditions imposed and ev evolves these conditions far more rapidly when applied individually than when applied simultaneously.I agree. However, the rapidity or slowness is uninteresting if you are not talking about evolving the same functional result of selection conditions.
It is interesting if you are considering monotherapy versus combination therapy for the treatment of HIV. It is also interesting if you want to understand how the mathematics of mutation and selection actually works. Now Paul, you have an opportunity to prove me wrong. All you have to do is apply the selection conditions in ev sequentially and cumulatively and show that you get some different function besides satisfying all three selection conditions far more rapidly than when the selection pressures are applied simultaneously.

[Taffer]

Taffer, you can’t tell the difference between mutation and selection and recombination and selection. Both are sorting problems. Mutation and selection is the sorting of beneficial and detrimental mutations while recombination and selection is the sorting of beneficial and detrimental alleles. One of the reason sorting of mutation and selection becomes so profoundly slow is the 4^G search space while recombination and selection has a much smaller search space because of the much, much smaller number of alleles that are being sorting. In addition, mating is often not random in the recombination and selection process giving even much more rapid morphological changes in the population. Dog breeding demonstrates this phenomenon. If you don’t like this example because of human involvement in the selection process, take Darwin’s own example of the variations of finch beaks which also demonstrates this phenomenon. Since you are having a hard time understanding the difference between mutation and selection and recombination and selection, here is a citation from a professor at Rice University.[/SIZE][/FONT]

http://www.rice.edu/sallyport/2007/winter/features/evolution.html (http://www.rice.edu/sallyport/2007/winter/features/evolution.html)


Professor Silberg understands how slow the sorting process for mutation and selection is and if a population needs to respond rapidly to a selection pressure, recombination is much more rapid.[/SIZE][/FONT]

Taffer, you also don’t understand that recombination without error can not create new information (alleles) in the gene pool and that recombination with natural selection can cause the loss of information (alleles) from the gene pool. Recombination with natural selection can not transform reptiles into birds. You need mutation and natural selection to make this metamorphosis. However, mutation and natural selection is profoundly slow if you have combination selection pressures, especially if you have small populations with slow reproductive times.

And here you once again show your misunderstanding. Yet again, it doesn't matter where variation arises, only that it exists. You harp on about "mutation and selection" and "recombination and selection" as if the selection mechanism acting is different. In reality, there is "mutation and recombination" and selection. Mutation and recombination are different mechanisms by which variation arises, then selection acts on that variation. That's why your endless harping about how my model only "models one kind" is wrong. You are wrong.

Care you address the model itself, or the rest of my points?

[Dr Adequate]

Running the model with no spurious binding mistakes gives almost every position bound not because they are being selected this way, it is because the threshold for the weight matrix is so low that it is very easy for the model to find matches. That’s why it takes only one generation to eliminate missed binding sites if that is the only selection condition imposed. Are you going to try to contend that selection is occurring in the nonbinding site region when the only selection condition is missed binding sites?

You keep trying to impose the condition of function on the mutation and selection process. The only function of selection is to improve the fitness of the population to reproduce. The ev model does not evolve realistic sequences of functioning genes whether you are using a single selection condition or all three selection conditions simultaneously. If you think there is another goal for the selection process than the improvement of the populations’ fitness to reproduce, then why did you post this on another thread?

Fitness to reproduce is the goal for the selection process, not some particular function.

You are the one saying that selection in ev must give a particular function. All ev does is try to give sequences of bases which satisfy the selection conditions, that’s the only function of these sequences of bases.

Would you expect a protease inhibitor to select for mutations in a reverse transcriptase inhibitor? What you are trying to do is link the selection pressures in ev which is an artificial linkage you are trying to make. If you have a single selection condition in the model which eliminates spurious binding in the nonbinding site region of the genome, the elimination of mistakes gives sequences of bases that don’t match the weight matrix, if you use all three selection conditions, convergence of the program still gives the same final condition in the nonbinding site region, that is no sequences of bases in the nonbinding site region that give a match to the weight matrix. That is the only function of the selection condition which eliminates spurious binding in the nonbinding site region of the genome. I look forward to you performing the experiment of applying the selection pressures sequentially and cumulatively, there’s your big opportunity to prove my hypothesis wrong. Of course we have the massive amount of empirical evidence which shows that sequential and cumulative selection pressures evolve much more rapidly than when the pressures are applied simultaneously.

The explanation for that is that with a wider binding site (and a wider weight matrix) you have fewer errors in the nonbinding site region for the same G. The only thing that changes in the model as you lengthen G is the number of spurious bindings you get in the nonbinding site region, the wider binding site reduces this number allowing you to converge larger genomes. If you want to call that the Rcapacity effect, comfort yourself with that thought. Regardless of the length of G, you can always evolve each of the selection conditions individually even when you can’t evolve the conditions simultaneously. That is the point. Single selection conditions evolve much more rapidly than combined selection conditions.

Of course not, you know full well that ev is not a biological organism and it is not evolving real binding sites. Ev only evolves sequences of bases that satisfy the selection conditions imposed and ev evolves these conditions far more rapidly when applied individually than when applied simultaneously. That is what you have gone into denial about what the ev model shows and that is why it would take years of cpu time to do an e coli size genome if you try to evolve all three selection conditions simultaneously. It also happens to be