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With all due respect...


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#1 Hypermere

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Posted 12 February 2006 - 12:39 AM


...most of the members here are like J.F.K...i.e., have a vision but get shot down. What I mean is that I am THE scientist in my area in this arena (soon) who will make some difference. My email is jfarrgator@yahoo.com. I don't see too many with my level of education in imminst, but at the same time I must say that if not for imminst I might have given up years ago. At any rate, I have a B.S. in Chemistry from the University of Florida 3.7 (damn you Playstation, I wanted the 4.0), including over three three years experience. Currently I study functional genomics of Zea maize currently and will start on my Master's here w/in 2 yrs. You all should know about our developing Aging Lab with Dr. Christiaan Leeuwenburgh, etc., awaiting their funding. I learned about CL via Dr. de Grey.

Any member of this site should communicate with me directly, especially if you have the education/understanding. Me, I believe it's the mitos. I have ideas, and would love to talk about them.

Oh by the way, major thank-u's to BJK for the videos, magnets, and calendars...they have/are being distributed.

If we die, whatever, but we might not! At any rate, let us spread the message to open minds and let our sisters and brothers "out of the box".

James P. Farrell-Horton
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(personal cell) 352-283-3280
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#2 John Schloendorn

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Posted 12 February 2006 - 01:40 AM

I don't see too many with my level of education in imminst

It's getting better all the time. Quite a few of us have started going to school for immortality, others have finished. I completely agree with you that we have the potential for much more discussion of hands-on research topics here and would greatly benefit from that.

Me, I believe it's the mitos. I have ideas, and would love to talk about them.

Great! Let's talk, here and now. What are you guys up to? What are your projects, plans, dreams after the maize is satisfactorily analyzed?

Just as a conversation starter, how do you see the role of mito dysfunction in the current number one age-related killers, heart disease, cancer, infectious diseases?

If you don't want to do this publicly, I'd be happy to get email from you. But remember, discussing this publicly is a great way to attract collaborators, and I bet there are more potential ones out there on imminst than you may think!

j

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#3 Hypermere

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Posted 12 February 2006 - 11:08 PM

I have not taken the time to do the 'quote' function. However, I do hope, as you hinted, that there are more potential collaborators @ imminst or anywhere else. The War Against Aging is the only war worth fighting...and unlike any other war, everyone wins.

I don't give a **** about corn, to be honest. I mean, it's important, and when I eat it, I see it the next day. Bottom line- I got a job and got in the system. I have and will continue to provide my current laboratory with permanent improvements and improve performance. (That is one of the things that I specialize in).

About the mitos...I'll start a general discussion topic:

Mitochondria *were* bacteria. Somewhere along the evolutionary tree, they merged with some cell, and hence today all of our cells contain at least one of them.

So, just like oil in the Mid-East, we need them for energy. Problem is that they are the prime suspect in the process of aging.

Begin your comments.

#4 Aegist

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Posted 13 February 2006 - 01:42 AM

I have just finished my honours in molecular biology. I also will be moving intoo research, and my goal atm is to build up knowledge of ow biotech companies work over the next 10 years or so, and then start my own longevity research based biotech company.

As for the mitochondrial thing, well, yes, need them, one of many potential causes of aging, but I think this is true of aging in general. I beleive that every one of the thousand elements that combine to create the ageing phenotype are a side effect of a beneficial trait. And the vast majority of these beneficial trais have become so ingrained in our evolutionary biology, that they simply cant be removed without killing us.

I strongly recomend that everyone who is anyone who has the slightest interest in ageing should read this paper.
http://www.telomere...._searchable.pdf
PLEIOTROPY, NATURAL SELECTION, AND THE EVOLUTION
OF SENESCENCE
Read it four times. It isnt too technical, and it puts aging right into evolutionary context. It was written in 1957, so its really old, and there are many much more modern papers, but I am yet to find one of them really add anything particularly special to this core paper.

Honestly, trained people, and lay people alike: everyone should read this if you are interested in ageing.

#5 eternaltraveler

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Posted 13 February 2006 - 02:35 AM

Do you have any thoughts on how to best mitigate the reactive oxygen species generated through oxidative phosphorylation? What do you think of the idea of allotropic expression of the mitochondrial genome? Do you have any thoughts on how this might be achomplished/would it be worth it?

#6 John Schloendorn

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Posted 13 February 2006 - 03:27 AM

While you're at it, how do you think allotopic expression would compare to protofection, in terms of delivery, feasibility, efficacy, safety?

#7 Hypermere

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Posted 13 February 2006 - 11:57 AM

ok now we are talking...you guys made my morning

#8 JonesGuy

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Posted 13 February 2006 - 04:56 PM

I'm rather certain that there is a lot more to the story than the mitos. Mainly because of how our germ-line does not age (if evolution is true).

If the mitos were a credible source of damage, then each germline cell would be minorly affected. This would be true, even if the protective measures in the germ cells is superior (some damage would get through) and if the cells select against damage (some cells would pass on, if there was undetectable damage).

However, since we see that the germ line is immortal, there must be sufficient 'potection' against mitos-caused damage.

Does that make any sense?

So, I really do believe that in some of our somatic cells, mitos cause damage ... but the fact that the damage accumulates is because of degradation of our protection systems.

Sadly, we seemingly cannot isolate the 'sufficient' protection system, because cell-selection seems to be a large component (and we lose that ability in somatic cells).

#9 John Schloendorn

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Posted 13 February 2006 - 08:50 PM

I'm rather certain that there is a lot more to the story than the mitos. Mainly because of how our germ-line does not age (if evolution is true).

Right, plus in many somatic mitotically active cell types, mito mutations simply don't accumulate like they do in post-mitotic cells, and thus would have a hard time accounting for age-related changes in those cells.

#10 JonesGuy

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Posted 13 February 2006 - 09:11 PM

We need to activate the ROS scrubbing effects without making cells cancerous. What's taking so long?

#11 Hypermere

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Posted 14 February 2006 - 01:01 AM

(To Another God), I'll be reading the Williams paper, contemplating, and comment at a future date (just printed the hardcopy).

To all, it is interesting that the topic discussion that I started is beginning to go over my head. But that is a good sign!

Anyone who saw Hollow Man might remember that genius is getting from A to D while skipping B & C. In other words, (as a lowly B.S. and Masters hopeful), it seems like maybe you guys are making things more complicated than they need to be, with all due respect. I will go to bed tonight dreaming about creating a worm or fly that never dies (unless it is eaten!).

#12 Aegist

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Posted 14 February 2006 - 01:28 AM

LOL. The first question asked was over my head. I had to use the infinite wisdom present in google to answer some of my own questions. This is one of the biggest problems I have experienced so far with studying molecular biology.... I still don't know anything. 4 years of full on study and I still feel like a layman. People ask me a question like how do you think ageing works, how do you think ROS can be scrubbed etc and my answers are as good as a layman who has read a random googled article.

Good to hear you are checking out that article hypermere. I dunno if its really weird or not, but I get excited every time I read that paper. I love it.

QJones and John, the immortality of the germline has always been a source of inspiration for me. Surely if our DNA can live forever, and it can produce fresh new cells forever, then surely there is hope that it can produce fresh new cells for our current body.

A rather fantasy like idea which would be cool if it was possible, is if we gould re-germinate ourselves oncew ever 40 years or so. And so instead of growing a brand new human, the germ cell was programmed to start replacing pre-existing cells in the body. The developmental program was re-written so that it would apoptise its neighbouring cells and grow outward, eventually replacing every cell in the body with cells from that grand new germline. This would give us a new body, but hopefully maintain the continuity of personal experience, since at no time the brain would be disrupted. (Unless consciousness/memory etc relies moreso upon inner-cellular activity rather than the relationship between cells.... or any other number of unforeseeable problems in brain chemistry)

#13 Hypermere

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Posted 15 February 2006 - 02:03 AM

Well we are on the same page, A.G., but at the same time, it is time to unleash our life-everlasting Egos. You may have noticed in my original post that I will be the One, and We all should think that way. I'm not trying to be a d***head, but, lead, follow, or get lost.
That old article is like a lost gem, I was reading it on the bus today, but i.m.o., I am with de Grey & Leeuwenburgh....mitos were bacteria, bacteria are, i.m.o., parasitic.
If I can think of a way to eliminate them and find 'alternative energy sources' (probably via advanced gene therapy), that would be fantastic.
Not to bring in 'religion', but even the bible says that the last enemy to be defeated is death (Corinthians). So even 'they' agree!
Dr. Kenyon has made the most advancement as far as I can see. Why only quadruple C. elegans lifespan....why stop there?
If you love to distrust your government, remember that death and aging is a big money-maker, like oil. So, don't trust anyone but yourself.
As for me, and hopefully for anyone reading this thread, I DO see myself at the Nobel Prize Presentation, thanking everyone who helped me.
Think outside of the box, and you have a chance. (And let us not forget the Singularity, which may have already begun). Peace, James.

#14 maestro949

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Posted 15 February 2006 - 02:12 AM

Right, plus in many somatic mitotically active cell types, mito mutations simply don't accumulate like they do in post-mitotic cells, and thus would have a hard time accounting for age-related changes in those cells.


Has any progress been made in identifying markers that indicate "age related changes" in general? Whether they be damage from ROS or mito mutations? If so, enumerating key tissues that fail and ranking them in order of most affected by aging and then targetting those as first candidates for repair or replacement seems like it would quickly yield results as to whether aging can be affected.

#15 John Schloendorn

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Posted 15 February 2006 - 02:42 AM

I will be the One, and We all should think that way.

I could not disagree more. Large-scale global collaboration is the only hope to achieve our intimidating goal.

If you love to distrust your government, remember that death and aging is a big money-maker, like oil.

How does aging make money for the government? On the contrary, aging costs us, by making age the primary risk factor for age-related diseases and frailty. It is thereby responsible for almost all public expenses of pensions, healthcare, and loss of tax-income from no longer-working individuals, which all have a massive detrimental impact on the finances of our administrative bodies.

Has any progress been made in identifying markers that indicate "age related changes" in general?

Progress yes, but still no adequate progress. Mortality and morbidity end-points are "by definition" what we're interested in, and even state of the art damage or biomarker endpoints do not always predict them very well in short-lived models (which could in part be because all known useful biomarkers are barely ever combined or weighed). In humans, both mortality and morbidity end-points themselves and the ability of biomarkers to predict them are exceptionally hard to assess, because we are so long lived. So it seems that we will be working in the dark for a long while, after which we will either find ourselves alive or dead. There does not seem to be much of a way around that, but some people (such as Kronos) are trying really hard to push the limits of the above logic.

#16 Hypermere

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Posted 15 February 2006 - 02:51 AM

Has any progress been made in identifying markers that indicate "age related changes" in general?


yeah, easily this can/probably has been done via 384-microarray plates, which ;) , I seek to gain access and training with.

#17 Hypermere

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Posted 15 February 2006 - 03:05 AM

I could not disagree more. Large-scale global collaboration is the only hope to achieve our intimidating goal.


I completely agree and disagree with you. When I mentioned ego's, I was also implying the global collaboration that you speak of.

As far as my reference to aging making money, you have to dig deeper in your own research, i.m.o. I am always willing to agree to disagree, but (especially if you understand neo-tech), "we live in a 2500 year-old anticivilization", which means that our current way of life is desperate for a quantum evolution. Basically, I believe that the 'old money' people are too far away in mental incapacitation, yet they control the world's finances, wars, etc.

If there were some magic box that made everyone live at the ~18-25 year-old level w/o ever declining....then doctors, hospitals, insurance companies, and more, would be in turmOIL. Agree or not, that's all I was attempting to convey.

Redtape, the FDA, and many other factors seem (again, only i.m.o.), to be keeping us stuck in the cave.

#18 maestro949

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Posted 15 February 2006 - 11:38 AM

Large-scale global collaboration is the only hope to achieve our intimidating goal.


I agree to some degree however human nature, ego, cyncism/suspicion of any organization and stories of heroic breakthroughs by individuals tend to drive people towards thinking that if they too apply their talents individually then they can be the one to find a magic solution to such a vast and problem. "Large scale collaboration" ends up being thousands of of scientists and others working alone or in small groups pursuing many small leaps forward across many frontiers with funding being doled out piecemeal. I don't think this is necessarily a bad model as there isn't just one single bullet to eliminating death by aging but probably dozens or perhaps even hundreds. Large scale collaboration requires either governmental coordination, MNC's coming together to invest in the progress for financial gain or independent organations of NGOs and loosely affiliated non-profits like this one here. In my opinion, none of these will be our savior in terms of mounting a massive campaign against the diseases of aging which leaves us with our heroes at the edges of the frontier whether they be spokespeople for the cause or determined scienetists working on one particular niche or study making making micro advancments across the board.

I still don't know anything. 4 years of full on study and I still feel like a layman


Disturbing. I've spent 6 weeks reading a few key academic texts, googled a few dozen topics I'm interested in and already feel like I can start making some contributions at the macro-level.


Progress yes, but still no adequate progress. Mortality and morbidity end-points are "by definition" what we're interested in, and even state of the art damage or biomarker endpoints do not always predict them very well in short-lived models (which could in part be because all known useful biomarkers are barely ever combined or weighed).


As I suspected. So in essence it's more likely that there are many disperate markers (or even specific behaviors) that in conjunction tend to indicate the age of a cell or tissue and I further suspect that these vary from cell type to cell type across all species. That's very depressing if true.

In humans, both mortality and morbidity end-points themselves and the ability of biomarkers to predict them are exceptionally hard to assess, because we are so long lived.


But we do know many of the, i dunno, i'll make up a word here "macro-markers" that ultimately kill the elderly. Just googled and found that of the top 10 killers of elderly, 80% die from one of these...

diseases of the heart
malignant neoplasms (cancer)
cerebrovascular disease
chronic obstructive pulmonary disease
diabetes mellitus
atherosclerosis and nephritis
nephrotic syndrome and nephrosis

Obviously a long list but are there intermediary states or precursors to these? Hypothetical question to some degree as obviously there are many types of heart disease, cancer, etc and I'm sure each issue has it's own genesis but there must be some recognizable patterns in the degeneration of the processes at the cellular level.


So it seems that we will be working in the dark for a long while, after which we will either find ourselves alive or dead.


Ironically, this is the first state diagram I drew in my quest to model life :)

Live --> Dead

From there I went to...

Dying --> Dead

Things get really complex from there though :)

#19 Aegist

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Posted 15 February 2006 - 01:06 PM

That old article is like a lost gem

glad you like the williams paper. Doesnt it just make ageing so straight forward? I feel like knowing why things age is the first step towards figuring out 'how' things age. For instance, if you beleived that things aged because it was for the good of the species, then you could look for 'the ageing gene' and things like that. As soon as you know that ageing seems to evolved through antagonistic pleiotropy, well...that changes everything. You have to start looking at good genes and try to figure out what bad things they bring to the party with them.... Knowing the truth to why organisms started to age is key.

As for being THE scientist to make a difference, I have always lived my life through a confidant outlook. Without religion, you have to impose beleif upon yourself, and so I did that. Life would probably have been easier if I could beleive that God would get me through it, but I didn't, so I had to do it myself. Confidence and expectation of success are important. But I have long since given up any concern of being recognised for adding anything. As long as someone, somewhere acheives the goal, then for all I care I can have nothing to do with it, or everything to do with it and get no credit for it, it doesnt matter, just so long as it gets done, and I see the benefits of the treatment.

Disturbing. I've spent 6 weeks reading a few key academic texts, googled a few dozen topics I'm interested in and already feel like I can start making some contributions at the macro-level.

Well that was sorta my point. Thats all it takes to contribute on that level, google. What I have learnt from 4 years at uni has given me a lot of specific knowledge and facts and a random collection of information which in themselves don't add up to anything interesting. The only interesting stuff I can add to the conversation is stuff that anyone can read in google or key papers. Ask me a technical question about the production of Methyglyoxal in Saccharomyces cerevisiae, and I can tell you all about it. But thats not really helpful to anyone.

#20 maestro949

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Posted 15 February 2006 - 01:55 PM

What I have learnt from 4 years at uni has given me a lot of specific knowledge and facts and a random collection of information which in themselves don't add up to anything interesting.


You will draw on them at some point.

The only interesting stuff I can add to the conversation is stuff that anyone can read in google or key papers. Ask me a technical question about the production of Methyglyoxal in Saccharomyces cerevisiae, and I can tell you all about it. But thats not really helpful to anyone.


True it isn't. All the collective knowledge we currently have as simply a large set of datapoints is fairly useless until it can be creatively applied to solving problems. Only the human brain can do that at this point. With powerful tools like computers, teamwork, vision, hard work, YOUR knowledge combinde with creativity and resourceful approaches we will overcome aging.


A rather fantasy like idea which would be cool if it was possible, is if we gould re-germinate ourselves oncew ever 40 years or so.


Why does it have to be a fantasy? Killing off aged cells and replacing them with young healthy ones is a perfect approach to fighting aging. Hell, the killing part is easy though targetting specific cells may be a bit of challenge. Regermination via a nanobot delivered replacement cell is a bit futuristic and unrealistic with current tech but why not look to join or start a research project with stem cell replacement therapy. Growing organs for example would be a good first phase of such a replacement plan as artificial organs don't seem like they are the way to go. It's taken 40 years for us to get an artificial heart to keep someone alive 6 months. Grrr.

#21 Hypermere

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Posted 16 February 2006 - 12:55 AM

Confidence and expectation of success are important. But I have long since given up any concern of being recognised for adding anything. As long as someone, somewhere acheives the goal, then for all I care I can have nothing to do with it, or everything to do with it and get no credit for it, it doesnt matter, just so long as it gets done, and I see the benefits of the treatment.


Same here. If, e.g., I were to solve the problem overnight, I would not seek a cent in profit...quite unlike big pharma companies! My payoff would be that it was done. Anyone of a genuine scientific mind who truly cares about humanity could say nothing to the contrary.

Now, remember that SETI program, where individual's PCs are used to scan the Universe for signs of life? I just moments ago read about a new program that similarly will provide information about global climate change.

Although one/many human minds may solve aging, I daydream about connecting multiple supercomputers, and "in layman's expression" asking it to solve death.

So one question to ask is:

How/who/when could a SETI-like network be established, which would ultimately be god-like, and may solve our problems quite soon. I am not as computer-savvy as some, but it's an idea.

And, again doubting government leaders, of course they could have done this years ago, and maybe already have and kept the secrets to themselves. Who knows.

#22 John Schloendorn

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Posted 16 February 2006 - 12:55 AM

Maestro,

"Large scale collaboration" ends up being thousands of of scientists and others working alone or in small groups pursuing many small leaps forward across many frontiers with funding being doled out piecemeal.

You have no idea what we're doing already! The lysoSENS project currently involves collaborations between at least three world-leading and several smaller labs from different universities and these aren't just sunday afternoons' collaborations, but we actually discuss, coordinate, visit and send each other stuff all the time. Targeted Methuselah Foundation funds are in this way allocated at high leverage, interdisiplinary projects carefully desined to give us the most bang for our buck. If anything, then the situation is set to grow and improve.

In my opinion, none of these will be our savior in terms of mounting a massive campaign against the diseases of aging

Maybe, but some one has to start trying, now. This ball is rolling, roll with it. The more, the merrier!

#23 maestro949

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Posted 16 February 2006 - 08:13 AM

Same here.  If, e.g., I were to solve the problem overnight, I would not seek a cent in profit...quite unlike big pharma companies!  My payoff would be that it was done.  Anyone of a genuine scientific mind who truly cares about humanity could say nothing to the contrary.


Very noble but wouldn't you expect at least a means to support yourself and your family to do the work to solve the problem? Or do you think you will solve or even make significant progress towards finding the silver bulley for the aging cure in your spare time? As far as big pharma, pleh...


Although one/many human minds may solve aging, I daydream about connecting multiple supercomputers, and "in layman's expression" asking it to solve death.


A computer is a tool. Like a calculator. Like a hammer. You input engergy into in the form of data and algorithms and it can do calculations for you faster than you could do them by hand. A computer will not solve problems without first building a mathematical model of the problem you are trying to solve.

So one question to ask is:

How/who/when could a SETI-like network be established, which would ultimately be god-like, and may solve our problems quite soon.  I am not as computer-savvy as some, but it's an idea.


There are still too many large gaps in our knowledge of microbiology, chemistry and physics to build a complete model but many believe we're reaching a point where there's enough information to start building models that will help us predict the remaining unsolved mysteries. Probably the closest thing to SETI-like projects are the distributed computing projects trying to understand the incredibly complex process of protein folding.

And, again doubting government leaders, of course they could have done this years ago, and maybe already have and kept the secrets to themselves.  Who knows.


I doubt it. Most governments rely on and pour tax revenue into the creativity and innovation of the academic/scientific communities and free markets to move the ball forward and when they do hire armies of scientists, the goals are not typically focused on solving aging issues but rather tend to be nationalist in terms of producing technology for the sake of militeristic and economic goals or espionage.

You have no idea what we're doing already!


Not fully but I've skimmed through some of the threads. Kudos to you for working on such an innitiative. I thought of going out into my back yard and digging up some of the bat guano under my bathouse and sending it in but it's currently buried under a foot of snow!

The lysoSENS project currently involves collaborations between at least three world-leading and several smaller labs from different universities and these aren't just sunday afternoons' collaborations, but we actually discuss, coordinate, visit and send each other stuff all the time. Targeted Methuselah Foundation funds are in this way allocated at high leverage, interdisiplinary projects carefully desined to give us the most bang for our buck. If anything, then the situation is set to grow and improve.


Both are great efforts and I really hope they can demonstrate how progress can be made independently of the status-quo power structures that currently rule the universe. I truly believe that the future of progress lies not in nationalistic governments nor corporate interests but rather in networks of forward-thinking individuals, benevolent organizations and academia leading us out of this dark-age of profit-driven economics where the underlying assumtions are that selfishness-leads-to-progress.

#24 JonesGuy

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Posted 16 February 2006 - 04:47 PM

Re: the dirt. The faster you send it to him, the faster he can get the data out. It's worth doing sooner, rather than later, because of compounding returns.

#25 Hypermere

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Posted 16 February 2006 - 11:36 PM

A computer is a tool. Like a calculator. Like a hammer. You input engergy into in the form of data and algorithms and it can do calculations for you faster than you could do them by hand. A computer will not solve problems without first building a mathematical model of the problem you are trying to solve.


Again, I have to bring up the Singularity here. Specifically, having a computer that far surpasses any and all human minds (there are Imminst forums addressing this). So, say we forgot about all this mathematical modeling, and just make the "Singuputer", which will in turn access all of the databases of existing knowledge about genomics, proteomics, etc. It does the work, and we reap the benefits. That is what I was attempting to convey.

#26 maestro949

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Posted 17 February 2006 - 01:59 PM

So, say we forgot about all this mathematical modeling, and just make the "Singuputer", which will in turn access all of the databases of existing knowledge about genomics, proteomics, etc.  It does the work, and we reap the benefits.  That is what I was attempting to convey.


Tell me how you make this Singuputer without math? Knowledge without application is useless.

#27 Hypermere

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Posted 18 February 2006 - 01:37 AM

Hell if I know, I'm a molecular biologist, not a programmer. All I assume is that if you link up lots of computers, you get one that is many-folds times better than anyone alone. If any members will correct/confirm/elaborate this concept, let me know. I heard (bear in mind that this may not be true) that it is illegal to link up more than a certain number of X-Boxes b/c a supercomputer would result.
Maybe I will do some research (or someone more CPU-knowledgeable) will research into how SETI originated, and suggest how this can be applied to the aging disease.

#28 th3hegem0n

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Posted 18 February 2006 - 02:39 AM

Again, I have to bring up the Singularity here. Specifically, having a computer that far surpasses any and all human minds (there are Imminst forums addressing this). So, say we forgot about all this mathematical modeling, and just make the "Singuputer", which will in turn access all of the databases of existing knowledge about genomics, proteomics, etc. It does the work, and we reap the benefits. That is what I was attempting to convey.


This statement displays a DRASTIC misunderstanding of the technological Singularity.

You are referring to something entirely, completely different.

http://www.singinst....ingularity.html

#29 Hypermere

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Posted 18 February 2006 - 07:36 AM

This statement displays a DRASTIC misunderstanding of the technological Singularity.

You are referring to something entirely, completely different.


Please elaborate.

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#30 Hypermere

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Posted 18 February 2006 - 07:38 AM

BJK, if you are keeping up w/this thread, please do step in and help clarify who is right, wrong, or none of the above.




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