Re:Caffeine toxicity - material safety data
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The Plague of Frogs
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· Score: 1
Based on the 75 mg/kg number, that means the LD50 of coffee for a 150lb. (67kg) person would be about 25 STRONG cups (200mg apiece). The LD50, BTW, is if you were to take 100 people in cages and give them all a dose of drug, the dose at which 50 people would be killed. Of course, this is more along the lines of the caffeine extracted from 25 cups of coffee injected into your veins at once. Or about 67 cans of Jolt. I could imagine that being fatal...
I don't understand what you're trying to say. Quantum holography is based on downconversion of photons to pairs of photons. This does not happen in any biological system, the brain included.
One really cool old experiment was when Hall showed that if you take a strip of metal in a magnetic field and send current through it, there will be a voltage difference between the two sides of the strip. Based on only this, it was determined that the charge carrying particle in "electricity" is the electron. It might not be quite as cool as Millikan's oil drop experiment, but it shows something mind-bogglingly fundamental with an extremely simple apparatus.
I simply don't believe that the human mind is as plain as you would like to paint it.
I'm doing my phd in theoretical and computational neuroscience, so I know a lot about the human brain (rigorously discussing the relationship between brain and mind is a can of worms I don't want to open here). My point is that you "simply not believing" something is based on intuitive beliefs rather than scientific data. People before Einstein simply couldn't believe that gravity could bend light, or that time goes slower on a mountaintop than at sea level. The fundamental principles of organization and function of the human brain are well understood, whether or not you choose to believe it. It's just that they're SO DAMN COMPLICATED. The brain is a physical system, like an anthill or a microchip. It is extremely complex, but this does not give it mystical powers beyond what would be possible by the normal laws of physical reality. People can't bend spoons with their mind or magically read each other's minds. This is difficult to experimentally "prove," but no one has ever been able to prove that they could do anything supernatural (for a sensationalistic spin on it, check out James Randi's million dollar challenge). My point is that the functions of the brain are well understood enough that there is no big mysterious void in scientific knowledge where the substrates of psychic ability are likely to be hiding.
And I agree with the other reply... the distinction between science and esp is that I can write down what I observed, explain it with math, and send it to someone across the world who can duplicate my experiments, and get the same answers from that math. If you could do that with ESP, we would use it instead of telecommunications satellites. Oh yeah, explain orbits without math.
I essentially agree with you, but I want to point out that not everything has to be explained with math to be science. It just has to be explained by a falsifiable model, which may or may not be mathematical in nature. Many of the greatest scientific discoveries involved no math at all. Like when Pasteur discovered chirality, or whoever it was discovered that maggots don't grow on meat unless you let flies lay eggs there. Before this simple experiment, people actually thought maggots spontaneously arose from rotting meat! To this day, there are scientific fields (such as immunology) in which mathematical models are simply not that useful. More to the point, though, lack of mathematical sophistication is not the problem causing the lack of public science knowledge. We're talking about whether or not the earth orbits the sun, or whether or not tomatoes contain genes. Or whether or not "intelligent design theory" (creationism) deserves to be taught in science classrooms. These are basic concepts that the public is not understanding, not things that require a lot of math to grasp.
But look here [psiexplorer.com] for more. I do, however, think that there is too much that we don't know or don't understand about our own minds to say these ideas are all "fake".
You might think so, in which case your opinions are at odds with massive amounts of data on the topic. If you don't know the neuroscience literature, that's fine. But acknowledge that your opinion is based on nothing but naive intuition.
And if Dr. Penrose is correct (and a LOT of people think he is), there are aspects of human consciousness that transcend mere matter.
As a computational neuroscience grad student, I can say that among serious scientists working on the brain, I've never heard of one who thinks Penrose is right. Personally, I think the guy should look at some data instead of postulating entire bizarre, implausible, and demonstrably false mechanisms based solely on thought experiments. Anyone who does not think the brain is complex enough to display the behaviors it does has not studied enough neurophysiology. I'm not saying the brain is deterministic, only that no one has provided any remotely compelling reason to believe that it could not function if it were.
Using fluorescence (shoot in photons of one wavelength, get photons of a different wavelength out) instead of reflectance, you can get past a couple of the hurdles limiting current CD technology. The most important one is the number of layers. DVDs can have only a couple of layers because of scattering, etc. If you use fluorescence, where the laser beam passes all the way through the disc, the photons coming out are of a different wavelength than the ones going in, so it's easy to filter them. The problem is that you need a way to select only a single layer of the disc to read. This can be done using confocal optics, where you excite multiple layers and filter out all but one. Unfortunately, this will lead to premature bleaching (destruction) of the disc, and a better alternative is to use two-photon excitation, where you excite only one layer. The idea is that if you can focus a laser of high enough power, two photons will hit the same dye molecule within several femtoseconds and create the same effect as one photon of twice the energy. The only place where the photons are concentrated enough to do this is at the very point where they're focused, so you only excite one spot. Of course, these lasers are extremely expensive and large, but there are ways to use cheaper lasers if you send the beam through a crystal that will downconvert each photon into two entangled photons so you can use entangled photons for the two-photon excitation. In general, this type of technology has been around for several years. Surprisingly enough, it's still WAY too expensive for the general public.
Two common ways this is done, depending on how fast you need it to be, are vibrating mirrors that scan the laser beam across the surface, and these things called AODs, or acousto-optic deflectors. My understanding is that it's a piezo crystal where you shine a laser beam through it, and it generates a diffraction pattern. However, how far the first harmonic splits off the axis of the beam is determined by how much current you are putting into the crystal, and everything but the first harmonic is thrown away. Using these, it's possible to redirect the path of a laser on a VERY fast timescale.
I seem to recall that scientists aren't exactly sure how aspirin works either.
The primary mechanism of aspirin is actually entirely understood and has been for quite a while. It is a non-competitive inhibitor of these enzymes cyclooxygenase 1 and 2 (COX for short), which catalyze formation of prostaglandins, mediators of the inflammatory response. However, COX-1 is not important in inflammation, but protects the lining of the stomach and intestines. After solving the structures of the two COX enzymes, scientists were able to design several molecules from scratch that would only inhibit COX-2 and not COX-1. These hit the market a couple years ago under the generic names celecoxib and rofecoxib, or trade names of Celebrex and Vioxx, for treatment of osteoarthritis. I think we've all seen the commercials.
If you want to take a drug that no one knows how it works, go for it. However, I will not be taking a drug that scientists are clueless about.
I wrote most of this in a different post, but it was too long and got cut off, so I figured I'd mention it again here. Scientists are not entirely clueless about how provigil works. Basically they know that it increases the firing rate of certain cells involved in regulation of wakefulness. However, they do not know the exact mechanism by which this works, and it's believed to be mediated by a bizarre mechanism in which the provigil molecules are intercalated into the cell membranes. So it's not some cutting edge, rationally designed, high-specificity drug like it sounds like it is. It's more of a low-specificity drug that acts on a downstream pathway, giving it less stimulant-type side effects. More importantly, it has numerous side effects including making you stupid. I took it for a few months for narcolepsy, and I became extremely slow-witted and depressed, and was eventually almost driven to suicide. It was only when my girlfriend figured out that it was the drug that was doing it that I stopped taking it and was okay. I also gave one to her once so she could stay up late and study for a big test, and it impaired her memory and thought processes and she ended up getting a terrible grade on the test. I think the slight stupefying effect happens to most people who take it, but only to a severe extent in some, but the point is that it is a very serious drug that should not be taken casually.
The Uberman sleep cycle thing is complete bullshit. There have been numerous REM deprivation studies done in animals, and what your brain and body really need is stage 4 sleep, not REM. REM is the lightest part of sleep, and stage 4 is the deepest. I'm a narcoleptic MD/PhD student studying neurophysiology, so I know a little about this stuff. If you want to be more efficient with your sleep, don't sleep more than four hours at a time. EEG studies have shown that four hours is about the optimum length of time for sleep, and it becomes much less efficient after that. So if you can sleep for two four-hour periods per day, you are in very good shape. There are multiple lines of evidence supporting the fact that Homo sapiens in "nature" slept twice a day, including a periodic body temperature changes with a 12 hour period (you're always sleepier when your body temp. is just past its peak, IIRC). Most people get very tired after lunch--this is not a coincidence. Note that in many cultures, this is the sleeping pattern people have (e.g. the Siesta).
No one really knows for sure why all animals sleep (down to fruit flies and earthworms), especially since one would think it would be strongly selected against, evolutionarily speaking. The fact that we spend 1/3 of our day defenseless shows just how important sleep is (that and the fact that sleep deprivation is fatal in all organisms from humans down to fruit flies). Interestingly, even birds that fly for days on end or whales that have to swim to the surface to breathe still sleep. However, their brains are capable of sleeping one hemisphere at a time! Another interesting/random fact is that hibernation is different than sleep because at least some animals that hibernate wake up out of their hibernation periodically and sleep for a day, then wake up again and hibernate some more. Apparently the hibernation and sleep are distinguishable by EEG (recording "brain waves" by scalp electrode). Most evidence points towards sleep's most important role being in consolidation of memory in cortex (and probably general homeostasis of neurons). People used to think this occurred during REM, but now it sounds more like this is occurring during different stages of sleep, while REM is more like a waking state where information is filtered and organized and prepared for consolidation in deeper stages of sleep. Your conscious perception of these processes occurring is called "dreams," BTW, and contrary to common belief, they do not happen exclusively during REM sleep. The reason why we need "sleep," a period of inactivity, is apparently because there simply isn't a way to perform certain tasks of homestasis, synaptic strength updating, etc. while the network is functional. This makes sense if you think about it, and apparently there's some interesting data supporting. Destexhe and Sejnowski have a book about some of this stuff, and I think they argue that pyramidal cells in cortex receive synchronous excitatory and inhibitory inputs from the intralaminar nuclei and reticular nucleus, respectively. Both of those are parts of the thalamus, a structure in the middle of the brain that sends some projections out to the cortex, or the layers of cells on the surface. Anyway, the excitatory input activates NMDA receptors and voltage-gated calcium channels in the dendrites, while the inhibitory input shunts the depolarization, preventing firing of action potentials. The dendrite therefore fills with calcium, activating various pathways involved in synaptic plasticity, etc.
But I digress. The point is, sleep is important, and just because there is a drug out there that can fool your brain into thinking it doesn't need sleep, it still does. Forced sleep deprivation, in time, has been shown to cause permanent brain damage and eventually death. Taking a drug like provigil will most likely not prevent these things from happening--it will only prevent you from knowing that these things are happening. Another thing is that some people will say that scientists don't know how provigil works. This is partly true. There was a paper in Cell (I think) a couple years ago demonstrating that provigil (also called modafinil) increases firing in cells expressing a certain receptor for hypocretin/orexin, this short peptide neurotransmitter that regulates various aspects of wakefulness and hunger. The neurons that make that stuff were recently shown to be the ones that mysteriously die in narcoleptic patients. However, we don't know the exact mechanism by which the provigil affects these cells. IIRC, the provigil doesn't interact directly with the receptor, but nonspecifically intercalates into the membranes and does who-knows-what, with one end result being increased firing rate in cells expressing the proper receptors. However, this drug is not some sort of high-specificity compound that was rationally designed or found by interaction with a known target like most of the new drugs coming out on the market. It may have many side effects that are not documented. I took it for several months, and it made me extremely stupid. I became severely depressed and was driven almost to suicide. I would just sit on the floor and cry, babbling that I used to be smart and I didn't know what was happening to me. The disturbing thing was that I somehow didn't realize that it was the drug doing it to me. Once my girlfriend figured this out and got me to stop taking it, I was fine. When I looked into it a little more, I found that there were a few people in narcolepsy support groups who had similar side effects, despite the fact that these were not reported during clinical trials (and therefore, my doctors had a hard time believing that they were real). In summary, stay away from provigil unless you need it. For the people it works for, it's a miracle drug, but it is a very serious drug, not just a caffeine pill.
Re:Titanium is also very flexible.
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The Sexiest Metal
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· Score: 1
I used to make some knives and things out of titanium alloys, and I worked with a few of them. Unalloyed titanium is closer to aluminum in strength and weight than it is to steel. Even titanium alloys are not nearly as strong as a piece of good steel the same size and shape, they're just a hell of a lot lighter (and rustproof). However, I made a friend a set of the 6-Al-4-V alloy wrist spikes when I was less "mature," and after sending them away to get them properly heat treated, their strength and weight baffled anyone who would pick them up and try to bend them. However, the original poster is right that the 50-50 nickel-Ti alloy "nitinol" is seriously cool. It's incredibly expensive to make and use, and I think it's pretty heavy, but you can do stuff like take a wire of it, dip it in cold water, then twist it into any shape and it will stay like that. Then you can dip it in hot water and it will go back to its original shape.
A couple of comments:
first, you're right that long-term expression of the target gene is difficult to achieve. However, there are certain very important applications of gene therapy that only require transient expression of the transgene. One example is to regrow blood vessels to the heart, which is a recent success of gene therapy.
Second, long-term expression is only difficult to achieve if you're using certain techniques to introduce the transgenes (e.g. retroviruses). If you combine "cloning" with gene therapy, you can use more typical lab techniques for stable transfection to get around this problem for certain classes of diseases, most notably diseases which affect blood cells, such as sickle cell anemia or even AIDS, if you could re-introduce CCR5 negative T cells, for example. A recent paper in Cell demonstrated repopulation of bone marrow with transgenic embryonic stem cells expressing the HoxB4 gene, which would make this possible in the absence of the Bush administration. And if we can figure out how to get hematopoietic stem cells (the blood-making stem cells in bone marrow) to proliferate in a dish forever, we can solve this problem without cloning.
So basically what I'm saying is that the real stumbling block in generalized gene therapy (stable transfection in vivo) has not been overcome, and you're right that this is a long way off. However, there are important types of gene therapy that do not require this, and they are either already here or will be here shortly.
The US has laws limiting embryonic stem cell research. They don't care if use use cells from yourself
This is one of the many misconceptions regarding this technology that is perpetuated to bias the public against it. One of the general strategies is to take cells from yourself and de-differentiate them, then do your gene therapy in a dish and re-introduce the cells. This gets around many of the problems of gene therapy because introducing genes into cells in a dish is easy, but introducing them into cells in a living human has rarely been done successfully. The problem is that opponents of this technology prefer to think of the process of de-differentiating your cells as cloning an army of little single-celled people since those cells from your arm could theoretically grow into humans, IF they were implanted into a human uterus under the right conditions. So cells from yourself actually ARE embryonic stem cells in certain cases. We don't have to use this strategy in all cases; SCID is an easy target for gene therapy as diseases go. It was first cured using gene therapy about two years ago in France. Funny how little press the successes of gene therapy get compared to the failures. However, any gene therapy of this type for any disease other than the SCIDs will require either breaking US laws regarding embryonic stem cells or the development of new technologies to circumvent this limitation. Of course, this is irrelevant because neither of these things will happen. Scientists in other countries (including recently-relocated American scientists) will simply beat us to it.
There is one serious flaw in DNA computing that people are sweeping under the rug, and that's that although the amount of time needed to solve the problem does not increase exponentially, the amount of DNA does. Off the top of my head, I don't know the amount of DNA needed to perform a given calculation, but one of my professors who works on this sort of thing showed us once that a calculation that could be done in a reasonable amount of time on a standard desktop computer would require more DNA than there is on earth. I'm sure there are ways to increase the efficiency of the process, but this is still a fundamental limitation of this type of computing.
Re:Biologists and Psychologists Abuse this...
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Digital Biology
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I'm sorry, DNA can obviously be percieved as a digital sequence. There are four distinct states encoding the information. ("recipe", whatever) I hope it's clear that it's not analog at least.
This statement is formally correct, but highly misleading. The whole digital vs. analog paradigm implies that DNA simply contains a signal as a function of position, but this is not the case. It's an actual molecule in the real world; the conformation of the molecule matters for important things like transcriptional regulation. This is more easily illustrated with protein sequences. They are also "digital," with twenty states instead of four. However, the behavior of protein molecules of known sequence is not ab initio predictable in practice for sequences of any useful length.
Re:Biologists and Psychologists Abuse this...
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Digital Biology
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The computer is exactly the same in both cases. The genome is interpreted differently in muscle cells and neurons because the genome itself turns on or off parts of itself in different places in the body.
I think I agree with everything except one point, and some lack of clarity in my previous post is getting in the way. The only thing (besides the genome itself) that has not changed between neurons and myocytes is the underlying laws of physics. Whether or not it is your intention, I think this is the computer you're referring to, which is what I ultimately agree with. When I said the computer has changed, I was referring to the idea that the things that actually act directly on the genome were the computer, i.e. the transcription factors and RNA polymerase. Since both of us think that's incorrect, we can stick to the idea that the computer is analogous to underlying physical laws. What you're saying is that the different transcription factors and so forth that mediate differentiation are also in software, which I agree with too. I think we actually agree on all of that. The one difference is that you're arguing that there's no difference between a program and data accessed by a program, so the genome is like a program written in an interpreted language. Actually, I can agree with that too, in a formal sense. The problem is that this argument can be extrapolated all the way out to any deterministic system, and almost anything can be analogous to a computer program. So what's the point of the analogy?
I think the issue is less whether the analogy is formally correct at some arbitrarily abstract level and more whether it's a "good" analogy or not. A human being and a donut are topologically equivalent (donut hole:mouth->anus), but I'm not aware of any analogy based on that fact that most people would call "good." If you say that the genome is analogous to a program written in a very high-level interpreted language that partially codes for its own interpreter (e.g. photoshop macro language with extensions), then I would agree that this could be formally valid. Nevertheless, it's a bad analogy. First, it's not specific to the genome--almost anything can be said to be analogous to a computer program if you apply that level of abstraction. More importantly, it's misleading. Unless you already understand a significant amount about molecular biology and computer science, the analogy is going to mislead you. The genome:computer program analogy is bad, and no number of pop science books is going to change that. Of course, it may be much better than the genome:immortal soul or genome:collective unconscious analogies...
Re:Biologists and Psychologists Abuse this...
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Digital Biology
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I agree with most of what you're saying, but I think there's a fundamental hole in your logic. If one is to believe that the genome is a computer program, then the cell must be the computer. Or, more precisely, the transcriptional machinery the previous poster mentioned, in addition to signal transduction networks in the cytoplasm, epigenetic influences, and a few other things are part of the computer that runs the program of the genome. But where are these things in the digital computer implementation you speak of? They're in SOFTWARE. In your example, a closer analogy is that of the computer to the laws of physics which regulate interactions among proteins and nucleic acids. The computer program is therefore analogous to the regulatory machinery of the cell, and the genome is analogous to data in an array (although the program can use the information in the array to modify its own code). In your example, the genome is NOT analogous to a computer program, but to data ACCESSED BY a program. This might seem like a subtle distinction, but it's really not. With a few exceptions, programs don't dramatically alter the setup or basic functions of the chip they're run on, but the genome does. In some sense, that's most of what the genome does. Neurons and muscle cells have the same "program," but the "computer" is different. That is one reason why the genome:program analogy is stupid. The geneticists you've been talking to almost certainly know better and should be more careful what they say.
Re:Biologists and Psychologists Abuse this...
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Digital Biology
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On some superficial level computer virus and DNA code analogies are good, but the problem is when people take them too far. What makes these analogies bad is that you don't have to take them very far to go too far. The computer virus analogy, to have any value, would require that programs are like cells, for example. They're not, at least in the important ways. The DNA code analogy is a very, very dangerous one that is emerging. Perhaps the best comparison I can make is to the brain-computer analogy. There are very few things more damaging to understanding of the brain than this intuitively appealing piece of idiocy. The DNA code analogy is already starting to lead people astray--I've seen papers from CS people making evolutionary arguments about coding in base 2 vs base 4 (ACTG = 4 bases) and that kind of thing, but the arguments are completely irrelevant because they take one detail and ignore everything else of what's known about the biochemistry of nucleic acids and the molecular biology of cells. Bad analogies are dangerous because they poison the way people think. Unfortunately, since biological systems are invariably orders of magnitude more complex than the systems they're being compared to, it's usually the conceptual understanding of the biological issues that suffers and not the other way around.
Re:Be careful not to take this too far.
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Digital Biology
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One comment that complements the previous post is that it is important to distinguish between computational biology and what the book is calling "digital biology." Computational biology is doing biology with computer models. "Digital biology" is doing CS using certain techniques inspired by biological systems. That does not make it biology. The book would be more appropriately titled "biological digitalism."
But I expected better from many of you. They aren't doing this to increase their population. They aren't even doing this for stem cell research per se. They have plenty of stem cells from their very aggressive population control program. No, what they want is money. They want to clone embryos to sell to us squeamish westerners.
Statements like this disturb me a little. Why is it that we automatically assume that researchers in China have such unholy motives? Maybe they think it's interesting science with great potential to improve people's lives, the same as most of us in the West.
China is not looking to increase their population (which they have difficulty controlling or feeding as is now)... they are doing research to A) Best the US and Europe at their own game, and B) come up with medical breakthrough that meet condition A and benefit their own society as well... maybe even boost their economy with something original that only they can produce, that being working genetic medicines they for once control under patent
Or alternatively, maybe there are no red or yellow menaces at work, simply scientists who happen to be Chinese, doing the same work as scientists who happen to be American, European, etc.
There are strains of smallpox that exist in the lab, but the virus no longer exists in nature. The last case of smallpox was in 1979, except for a lab-related case in the 1980's.
The fact is that we just don't know what will happen if we do this, and applying half-knowledge to a problem can only make it worse.
The fact is that YOU don't know what will happen. It's important to understand that there are people in the world who know things you don't.
Based on the 75 mg/kg number, that means the LD50 of coffee for a 150lb. (67kg) person would be about 25 STRONG cups (200mg apiece). The LD50, BTW, is if you were to take 100 people in cages and give them all a dose of drug, the dose at which 50 people would be killed. Of course, this is more along the lines of the caffeine extracted from 25 cups of coffee injected into your veins at once. Or about 67 cans of Jolt. I could imagine that being fatal...
I don't understand what you're trying to say. Quantum holography is based on downconversion of photons to pairs of photons. This does not happen in any biological system, the brain included.
One really cool old experiment was when Hall showed that if you take a strip of metal in a magnetic field and send current through it, there will be a voltage difference between the two sides of the strip. Based on only this, it was determined that the charge carrying particle in "electricity" is the electron. It might not be quite as cool as Millikan's oil drop experiment, but it shows something mind-bogglingly fundamental with an extremely simple apparatus.
I simply don't believe that the human mind is as plain as you would like to paint it.
I'm doing my phd in theoretical and computational neuroscience, so I know a lot about the human brain (rigorously discussing the relationship between brain and mind is a can of worms I don't want to open here). My point is that you "simply not believing" something is based on intuitive beliefs rather than scientific data. People before Einstein simply couldn't believe that gravity could bend light, or that time goes slower on a mountaintop than at sea level. The fundamental principles of organization and function of the human brain are well understood, whether or not you choose to believe it. It's just that they're SO DAMN COMPLICATED. The brain is a physical system, like an anthill or a microchip. It is extremely complex, but this does not give it mystical powers beyond what would be possible by the normal laws of physical reality. People can't bend spoons with their mind or magically read each other's minds. This is difficult to experimentally "prove," but no one has ever been able to prove that they could do anything supernatural (for a sensationalistic spin on it, check out James Randi's million dollar challenge). My point is that the functions of the brain are well understood enough that there is no big mysterious void in scientific knowledge where the substrates of psychic ability are likely to be hiding.
And I agree with the other reply... the distinction between science and esp is that I can write down what I observed, explain it with math, and send it to someone across the world who can duplicate my experiments, and get the same answers from that math. If you could do that with ESP, we would use it instead of telecommunications satellites. Oh yeah, explain orbits without math.
I essentially agree with you, but I want to point out that not everything has to be explained with math to be science. It just has to be explained by a falsifiable model, which may or may not be mathematical in nature. Many of the greatest scientific discoveries involved no math at all. Like when Pasteur discovered chirality, or whoever it was discovered that maggots don't grow on meat unless you let flies lay eggs there. Before this simple experiment, people actually thought maggots spontaneously arose from rotting meat! To this day, there are scientific fields (such as immunology) in which mathematical models are simply not that useful. More to the point, though, lack of mathematical sophistication is not the problem causing the lack of public science knowledge. We're talking about whether or not the earth orbits the sun, or whether or not tomatoes contain genes. Or whether or not "intelligent design theory" (creationism) deserves to be taught in science classrooms. These are basic concepts that the public is not understanding, not things that require a lot of math to grasp.
But look here [psiexplorer.com] for more. I do, however, think that there is too much that we don't know or don't understand about our own minds to say these ideas are all "fake".
You might think so, in which case your opinions are at odds with massive amounts of data on the topic. If you don't know the neuroscience literature, that's fine. But acknowledge that your opinion is based on nothing but naive intuition.
And if Dr. Penrose is correct (and a LOT of people think he is), there are aspects of human consciousness that transcend mere matter.
As a computational neuroscience grad student, I can say that among serious scientists working on the brain, I've never heard of one who thinks Penrose is right. Personally, I think the guy should look at some data instead of postulating entire bizarre, implausible, and demonstrably false mechanisms based solely on thought experiments. Anyone who does not think the brain is complex enough to display the behaviors it does has not studied enough neurophysiology. I'm not saying the brain is deterministic, only that no one has provided any remotely compelling reason to believe that it could not function if it were.
Using fluorescence (shoot in photons of one wavelength, get photons of a different wavelength out) instead of reflectance, you can get past a couple of the hurdles limiting current CD technology. The most important one is the number of layers. DVDs can have only a couple of layers because of scattering, etc. If you use fluorescence, where the laser beam passes all the way through the disc, the photons coming out are of a different wavelength than the ones going in, so it's easy to filter them. The problem is that you need a way to select only a single layer of the disc to read. This can be done using confocal optics, where you excite multiple layers and filter out all but one. Unfortunately, this will lead to premature bleaching (destruction) of the disc, and a better alternative is to use two-photon excitation, where you excite only one layer. The idea is that if you can focus a laser of high enough power, two photons will hit the same dye molecule within several femtoseconds and create the same effect as one photon of twice the energy. The only place where the photons are concentrated enough to do this is at the very point where they're focused, so you only excite one spot. Of course, these lasers are extremely expensive and large, but there are ways to use cheaper lasers if you send the beam through a crystal that will downconvert each photon into two entangled photons so you can use entangled photons for the two-photon excitation. In general, this type of technology has been around for several years. Surprisingly enough, it's still WAY too expensive for the general public.
Two common ways this is done, depending on how fast you need it to be, are vibrating mirrors that scan the laser beam across the surface, and these things called AODs, or acousto-optic deflectors. My understanding is that it's a piezo crystal where you shine a laser beam through it, and it generates a diffraction pattern. However, how far the first harmonic splits off the axis of the beam is determined by how much current you are putting into the crystal, and everything but the first harmonic is thrown away. Using these, it's possible to redirect the path of a laser on a VERY fast timescale.
I seem to recall that scientists aren't exactly sure how aspirin works either.
The primary mechanism of aspirin is actually entirely understood and has been for quite a while. It is a non-competitive inhibitor of these enzymes cyclooxygenase 1 and 2 (COX for short), which catalyze formation of prostaglandins, mediators of the inflammatory response. However, COX-1 is not important in inflammation, but protects the lining of the stomach and intestines. After solving the structures of the two COX enzymes, scientists were able to design several molecules from scratch that would only inhibit COX-2 and not COX-1. These hit the market a couple years ago under the generic names celecoxib and rofecoxib, or trade names of Celebrex and Vioxx, for treatment of osteoarthritis. I think we've all seen the commercials.
If you want to take a drug that no one knows how it works, go for it. However, I will not be taking a drug that scientists are clueless about.
I wrote most of this in a different post, but it was too long and got cut off, so I figured I'd mention it again here. Scientists are not entirely clueless about how provigil works. Basically they know that it increases the firing rate of certain cells involved in regulation of wakefulness. However, they do not know the exact mechanism by which this works, and it's believed to be mediated by a bizarre mechanism in which the provigil molecules are intercalated into the cell membranes. So it's not some cutting edge, rationally designed, high-specificity drug like it sounds like it is. It's more of a low-specificity drug that acts on a downstream pathway, giving it less stimulant-type side effects. More importantly, it has numerous side effects including making you stupid. I took it for a few months for narcolepsy, and I became extremely slow-witted and depressed, and was eventually almost driven to suicide. It was only when my girlfriend figured out that it was the drug that was doing it that I stopped taking it and was okay. I also gave one to her once so she could stay up late and study for a big test, and it impaired her memory and thought processes and she ended up getting a terrible grade on the test. I think the slight stupefying effect happens to most people who take it, but only to a severe extent in some, but the point is that it is a very serious drug that should not be taken casually.
The Uberman sleep cycle thing is complete bullshit. There have been numerous REM deprivation studies done in animals, and what your brain and body really need is stage 4 sleep, not REM. REM is the lightest part of sleep, and stage 4 is the deepest. I'm a narcoleptic MD/PhD student studying neurophysiology, so I know a little about this stuff. If you want to be more efficient with your sleep, don't sleep more than four hours at a time. EEG studies have shown that four hours is about the optimum length of time for sleep, and it becomes much less efficient after that. So if you can sleep for two four-hour periods per day, you are in very good shape. There are multiple lines of evidence supporting the fact that Homo sapiens in "nature" slept twice a day, including a periodic body temperature changes with a 12 hour period (you're always sleepier when your body temp. is just past its peak, IIRC). Most people get very tired after lunch--this is not a coincidence. Note that in many cultures, this is the sleeping pattern people have (e.g. the Siesta).
No one really knows for sure why all animals sleep (down to fruit flies and earthworms), especially since one would think it would be strongly selected against, evolutionarily speaking. The fact that we spend 1/3 of our day defenseless shows just how important sleep is (that and the fact that sleep deprivation is fatal in all organisms from humans down to fruit flies). Interestingly, even birds that fly for days on end or whales that have to swim to the surface to breathe still sleep. However, their brains are capable of sleeping one hemisphere at a time! Another interesting/random fact is that hibernation is different than sleep because at least some animals that hibernate wake up out of their hibernation periodically and sleep for a day, then wake up again and hibernate some more. Apparently the hibernation and sleep are distinguishable by EEG (recording "brain waves" by scalp electrode). Most evidence points towards sleep's most important role being in consolidation of memory in cortex (and probably general homeostasis of neurons). People used to think this occurred during REM, but now it sounds more like this is occurring during different stages of sleep, while REM is more like a waking state where information is filtered and organized and prepared for consolidation in deeper stages of sleep. Your conscious perception of these processes occurring is called "dreams," BTW, and contrary to common belief, they do not happen exclusively during REM sleep. The reason why we need "sleep," a period of inactivity, is apparently because there simply isn't a way to perform certain tasks of homestasis, synaptic strength updating, etc. while the network is functional. This makes sense if you think about it, and apparently there's some interesting data supporting. Destexhe and Sejnowski have a book about some of this stuff, and I think they argue that pyramidal cells in cortex receive synchronous excitatory and inhibitory inputs from the intralaminar nuclei and reticular nucleus, respectively. Both of those are parts of the thalamus, a structure in the middle of the brain that sends some projections out to the cortex, or the layers of cells on the surface. Anyway, the excitatory input activates NMDA receptors and voltage-gated calcium channels in the dendrites, while the inhibitory input shunts the depolarization, preventing firing of action potentials. The dendrite therefore fills with calcium, activating various pathways involved in synaptic plasticity, etc.
But I digress. The point is, sleep is important, and just because there is a drug out there that can fool your brain into thinking it doesn't need sleep, it still does. Forced sleep deprivation, in time, has been shown to cause permanent brain damage and eventually death. Taking a drug like provigil will most likely not prevent these things from happening--it will only prevent you from knowing that these things are happening. Another thing is that some people will say that scientists don't know how provigil works. This is partly true. There was a paper in Cell (I think) a couple years ago demonstrating that provigil (also called modafinil) increases firing in cells expressing a certain receptor for hypocretin/orexin, this short peptide neurotransmitter that regulates various aspects of wakefulness and hunger. The neurons that make that stuff were recently shown to be the ones that mysteriously die in narcoleptic patients. However, we don't know the exact mechanism by which the provigil affects these cells. IIRC, the provigil doesn't interact directly with the receptor, but nonspecifically intercalates into the membranes and does who-knows-what, with one end result being increased firing rate in cells expressing the proper receptors. However, this drug is not some sort of high-specificity compound that was rationally designed or found by interaction with a known target like most of the new drugs coming out on the market. It may have many side effects that are not documented. I took it for several months, and it made me extremely stupid. I became severely depressed and was driven almost to suicide. I would just sit on the floor and cry, babbling that I used to be smart and I didn't know what was happening to me. The disturbing thing was that I somehow didn't realize that it was the drug doing it to me. Once my girlfriend figured this out and got me to stop taking it, I was fine. When I looked into it a little more, I found that there were a few people in narcolepsy support groups who had similar side effects, despite the fact that these were not reported during clinical trials (and therefore, my doctors had a hard time believing that they were real). In summary, stay away from provigil unless you need it. For the people it works for, it's a miracle drug, but it is a very serious drug, not just a caffeine pill.
I used to make some knives and things out of titanium alloys, and I worked with a few of them. Unalloyed titanium is closer to aluminum in strength and weight than it is to steel. Even titanium alloys are not nearly as strong as a piece of good steel the same size and shape, they're just a hell of a lot lighter (and rustproof). However, I made a friend a set of the 6-Al-4-V alloy wrist spikes when I was less "mature," and after sending them away to get them properly heat treated, their strength and weight baffled anyone who would pick them up and try to bend them. However, the original poster is right that the 50-50 nickel-Ti alloy "nitinol" is seriously cool. It's incredibly expensive to make and use, and I think it's pretty heavy, but you can do stuff like take a wire of it, dip it in cold water, then twist it into any shape and it will stay like that. Then you can dip it in hot water and it will go back to its original shape.
The only determiner of sex in baby mammals (and in birds afaik, as well) is which, of set (X,Y) chromosome
This is correct, except that in birds XY is the female and XX is the male.
A couple of comments: first, you're right that long-term expression of the target gene is difficult to achieve. However, there are certain very important applications of gene therapy that only require transient expression of the transgene. One example is to regrow blood vessels to the heart, which is a recent success of gene therapy.
Second, long-term expression is only difficult to achieve if you're using certain techniques to introduce the transgenes (e.g. retroviruses). If you combine "cloning" with gene therapy, you can use more typical lab techniques for stable transfection to get around this problem for certain classes of diseases, most notably diseases which affect blood cells, such as sickle cell anemia or even AIDS, if you could re-introduce CCR5 negative T cells, for example. A recent paper in Cell demonstrated repopulation of bone marrow with transgenic embryonic stem cells expressing the HoxB4 gene, which would make this possible in the absence of the Bush administration. And if we can figure out how to get hematopoietic stem cells (the blood-making stem cells in bone marrow) to proliferate in a dish forever, we can solve this problem without cloning.
So basically what I'm saying is that the real stumbling block in generalized gene therapy (stable transfection in vivo) has not been overcome, and you're right that this is a long way off. However, there are important types of gene therapy that do not require this, and they are either already here or will be here shortly.
disclaimer: iaamdphd
The US has laws limiting embryonic stem cell research. They don't care if use use cells from yourself
This is one of the many misconceptions regarding this technology that is perpetuated to bias the public against it. One of the general strategies is to take cells from yourself and de-differentiate them, then do your gene therapy in a dish and re-introduce the cells. This gets around many of the problems of gene therapy because introducing genes into cells in a dish is easy, but introducing them into cells in a living human has rarely been done successfully. The problem is that opponents of this technology prefer to think of the process of de-differentiating your cells as cloning an army of little single-celled people since those cells from your arm could theoretically grow into humans, IF they were implanted into a human uterus under the right conditions. So cells from yourself actually ARE embryonic stem cells in certain cases. We don't have to use this strategy in all cases; SCID is an easy target for gene therapy as diseases go. It was first cured using gene therapy about two years ago in France. Funny how little press the successes of gene therapy get compared to the failures. However, any gene therapy of this type for any disease other than the SCIDs will require either breaking US laws regarding embryonic stem cells or the development of new technologies to circumvent this limitation. Of course, this is irrelevant because neither of these things will happen. Scientists in other countries (including recently-relocated American scientists) will simply beat us to it.
There is one serious flaw in DNA computing that people are sweeping under the rug, and that's that although the amount of time needed to solve the problem does not increase exponentially, the amount of DNA does. Off the top of my head, I don't know the amount of DNA needed to perform a given calculation, but one of my professors who works on this sort of thing showed us once that a calculation that could be done in a reasonable amount of time on a standard desktop computer would require more DNA than there is on earth. I'm sure there are ways to increase the efficiency of the process, but this is still a fundamental limitation of this type of computing.
I'm sorry, DNA can obviously be percieved as a digital sequence. There are four distinct states encoding the information. ("recipe", whatever) I hope it's clear that it's not analog at least.
This statement is formally correct, but highly misleading. The whole digital vs. analog paradigm implies that DNA simply contains a signal as a function of position, but this is not the case. It's an actual molecule in the real world; the conformation of the molecule matters for important things like transcriptional regulation. This is more easily illustrated with protein sequences. They are also "digital," with twenty states instead of four. However, the behavior of protein molecules of known sequence is not ab initio predictable in practice for sequences of any useful length.
The computer is exactly the same in both cases. The genome is interpreted differently in muscle cells and neurons because the genome itself turns on or off parts of itself in different places in the body.
I think I agree with everything except one point, and some lack of clarity in my previous post is getting in the way. The only thing (besides the genome itself) that has not changed between neurons and myocytes is the underlying laws of physics. Whether or not it is your intention, I think this is the computer you're referring to, which is what I ultimately agree with. When I said the computer has changed, I was referring to the idea that the things that actually act directly on the genome were the computer, i.e. the transcription factors and RNA polymerase. Since both of us think that's incorrect, we can stick to the idea that the computer is analogous to underlying physical laws. What you're saying is that the different transcription factors and so forth that mediate differentiation are also in software, which I agree with too. I think we actually agree on all of that. The one difference is that you're arguing that there's no difference between a program and data accessed by a program, so the genome is like a program written in an interpreted language. Actually, I can agree with that too, in a formal sense. The problem is that this argument can be extrapolated all the way out to any deterministic system, and almost anything can be analogous to a computer program. So what's the point of the analogy?
I think the issue is less whether the analogy is formally correct at some arbitrarily abstract level and more whether it's a "good" analogy or not. A human being and a donut are topologically equivalent (donut hole:mouth->anus), but I'm not aware of any analogy based on that fact that most people would call "good." If you say that the genome is analogous to a program written in a very high-level interpreted language that partially codes for its own interpreter (e.g. photoshop macro language with extensions), then I would agree that this could be formally valid. Nevertheless, it's a bad analogy. First, it's not specific to the genome--almost anything can be said to be analogous to a computer program if you apply that level of abstraction. More importantly, it's misleading. Unless you already understand a significant amount about molecular biology and computer science, the analogy is going to mislead you. The genome:computer program analogy is bad, and no number of pop science books is going to change that. Of course, it may be much better than the genome:immortal soul or genome:collective unconscious analogies...
I agree with most of what you're saying, but I think there's a fundamental hole in your logic. If one is to believe that the genome is a computer program, then the cell must be the computer. Or, more precisely, the transcriptional machinery the previous poster mentioned, in addition to signal transduction networks in the cytoplasm, epigenetic influences, and a few other things are part of the computer that runs the program of the genome. But where are these things in the digital computer implementation you speak of? They're in SOFTWARE. In your example, a closer analogy is that of the computer to the laws of physics which regulate interactions among proteins and nucleic acids. The computer program is therefore analogous to the regulatory machinery of the cell, and the genome is analogous to data in an array (although the program can use the information in the array to modify its own code). In your example, the genome is NOT analogous to a computer program, but to data ACCESSED BY a program. This might seem like a subtle distinction, but it's really not. With a few exceptions, programs don't dramatically alter the setup or basic functions of the chip they're run on, but the genome does. In some sense, that's most of what the genome does. Neurons and muscle cells have the same "program," but the "computer" is different. That is one reason why the genome:program analogy is stupid. The geneticists you've been talking to almost certainly know better and should be more careful what they say.
On some superficial level computer virus and DNA code analogies are good, but the problem is when people take them too far. What makes these analogies bad is that you don't have to take them very far to go too far. The computer virus analogy, to have any value, would require that programs are like cells, for example. They're not, at least in the important ways. The DNA code analogy is a very, very dangerous one that is emerging. Perhaps the best comparison I can make is to the brain-computer analogy. There are very few things more damaging to understanding of the brain than this intuitively appealing piece of idiocy. The DNA code analogy is already starting to lead people astray--I've seen papers from CS people making evolutionary arguments about coding in base 2 vs base 4 (ACTG = 4 bases) and that kind of thing, but the arguments are completely irrelevant because they take one detail and ignore everything else of what's known about the biochemistry of nucleic acids and the molecular biology of cells. Bad analogies are dangerous because they poison the way people think. Unfortunately, since biological systems are invariably orders of magnitude more complex than the systems they're being compared to, it's usually the conceptual understanding of the biological issues that suffers and not the other way around.
One comment that complements the previous post is that it is important to distinguish between computational biology and what the book is calling "digital biology." Computational biology is doing biology with computer models. "Digital biology" is doing CS using certain techniques inspired by biological systems. That does not make it biology. The book would be more appropriately titled "biological digitalism."
But I expected better from many of you. They aren't doing this to increase their population. They aren't even doing this for stem cell research per se. They have plenty of stem cells from their very aggressive population control program. No, what they want is money. They want to clone embryos to sell to us squeamish westerners.
Statements like this disturb me a little. Why is it that we automatically assume that researchers in China have such unholy motives? Maybe they think it's interesting science with great potential to improve people's lives, the same as most of us in the West.
China is not looking to increase their population (which they have difficulty controlling or feeding as is now)... they are doing research to A) Best the US and Europe at their own game, and B) come up with medical breakthrough that meet condition A and benefit their own society as well... maybe even boost their economy with something original that only they can produce, that being working genetic medicines they for once control under patent
Or alternatively, maybe there are no red or yellow menaces at work, simply scientists who happen to be Chinese, doing the same work as scientists who happen to be American, European, etc.
Firstly - smallpox has not been wiped out.
There are strains of smallpox that exist in the lab, but the virus no longer exists in nature. The last case of smallpox was in 1979, except for a lab-related case in the 1980's.
The fact is that we just don't know what will happen if we do this, and applying half-knowledge to a problem can only make it worse.
The fact is that YOU don't know what will happen. It's important to understand that there are people in the world who know things you don't.