Posted on 03/15/2005 2:41:19 PM PST by Michael_Michaelangelo
The Future of Biology: Reverse Engineering 03/14/2005 Just as an engineer can model the feedback controls required in an autopilot system for an aircraft, the biologist can construct models of cellular networks to try to understand how they work. “The hallmark of a good feedback control design is a resulting closed loop system that is stable and robust to modeling errors and parameter variation in the plant”, [i.e., the system], “and achieves a desired output value quickly without unduly large actuation signals at the plant input,” explain Claire J. Tomlin and Jeffrey D. Axelrod of Stanford in a Commentary in PNAS.1 (Emphasis added in all quotes.) But are the analytical principles of reverse engineering relevant to biological systems? Yes, they continue: “Some insightful recent papers advocate a similar modular decomposition of biological systems according to the well defined functional parts used in engineering and, specifically, engineering control theory.”
One example they focus on is the bacterial heat shock response recently modeled by El-Samad et al.2 (see 01/26/2005 entry). These commentators seem quite amazed at the technology of this biological system: In a recent issue of PNAS, El-Samad et al. showed that the mechanism used in Escherichia coli to combat heat shock is just what a well trained control engineer would design, given the signals and the functions available.
This is no simple trick. “The challenge to the cell is that the task is gargantuan,” they exclaim. Thousands of protein parts – up to a quarter of the cell’s protein inventory – must be generated rapidly in times of heat stress. But like an army with nothing to do, a large heat-shock response force is too expensive to maintain all the time. Instead, the rescuers are drafted into action when needed by an elaborate system of sensors, feedback and feed-forward loops, and protein networks.
Living cells defend themselves from a vast array of environmental insults. One such environmental stress is exposure to temperatures significantly above the range in which an organism normally lives. Heat unfolds proteins by introducing thermal energy that is sufficient to overcome the noncovalent molecular interactions that maintain their tertiary structures. Evidently, this threat has been ubiquitous throughout the evolution [sic] of most life forms. Organisms respond with a highly conserved response that involves the induced expression of heat shock proteins. These proteins include molecular chaperones that ordinarily help to fold newly synthesized proteins and in this context help to refold denatured proteins. They also include proteases [enzymes that disassemble damaged proteins] and, in eukaryotes, a proteolytic multiprotein complex called the proteasome, which serve to degrade denatured proteins that are otherwise harmful or even lethal to the cell. Sufficient production of chaperones and proteases can rescue the cell from death by repairing or ridding the cell of damaged proteins.
The interesting thing about this Commentary, however, is not just the bacterial system, amazing as it is. It’s the way the scientists approached the system to understand it. “Viewing the heat shock response as a control engineer would,” they continue, El-Samad et al. treated it like a robust system and reverse-engineered it into a mathematical model, then ran simulations to see if it reacted like the biological system. They found that two feedback loops were finely tuned to each other to provide robustness against single-parameter fluctuations. By altering the parameters in their model, they could detect influences on the response time and the number of proteins generated. This approach gave them a handle on what was going on in the cell. The analysis in El-Samad et al. is important not just because it captures the behavior of the system, but because it decomposes the mechanism into intuitively comprehensible parts. If the heat shock mechanism can be described and understood in terms of engineering control principles, it will surely be informative to apply these principles to a broad array of cellular regulatory mechanisms and thereby reveal the control architecture under which they operate.
With the flood of data hitting molecular biologists in the post-genomic era, they explain, this reverse-engineering approach is much more promising than identifying the function of each protein part, because: ...the physiologically relevant functions of the majority of proteins encoded in most genomes are either poorly understood or not understood at all. One can imagine that, by combining these data with measurements of response profiles, it may be possible to deduce the presence of modular control features, such as feedforward or feedback paths, and the kind of control function that the system uses. It may even be possible to examine the response characteristics of a given system, for example, a rapid and sustained output, as seen here, or an oscillation, and to draw inferences about the conditions under which a mechanism is built to function. This, in turn, could help in deducing what other signals are participating in the system behavior.
The commentators clearly see this example as a positive step forward toward the ultimate goal, “to predict, from the response characteristics, the overall function of the biological network.” They hope other biologists will follow the lead of El-Samad et al. Such reverse engineering may be “the most effective means” of modeling unknown cellular systems, they end: “Certainly, these kinds of analyses promise to raise the bar for understanding biological processes.”
1Tomlin and Axelrod, “Understanding biology by reverse engineering the control,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0500276102, published online before print March 14, 2005.
2El-Samad, Kurata, Doyle, Gross and Khammash, “Surviving heat shock: Control strategies for robustness and performance,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0403510102, published online before print January 24, 2005. Reader, please understand the significance of this commentary. Not only did El-Samad et al. demonstrate that the design approach works, but these commentators praised it as the best way to understand biology (notice their title). That implies all of biology, not just the heat shock response in bacteria, would be better served with the design approach. This is a powerful affirmation of intelligent design theory from scientists outside the I.D. camp.
Sure, they referred to evolution a couple of times, but the statements were incidental and worthless. Reverse engineering needs Darwinism like teenagers need a pack of cigarettes. Evolutionary theory contributes nothing to this approach; it is just a habit, full of poison and hot air. Design theory breaks out of the habit and provides a fresh new beginning. These commentators started their piece with a long paragraph about how engineers design models of aircraft autopilot systems; then they drew clear, unambiguous parallels to biological systems. If we need to become design engineers to understand biology, then attributing the origin of the systems to chance, undirected processes is foolish. Darwinistas, your revolution has failed. Get out of the way, or get with the program. We don’t need your tall tales and unworkable utopian dreams any more. The future of biology belongs to the engineers who appreciate good design when they see it.
It’s amazing to ponder that a cell is programmed to deal with heat shock better than a well-trained civil defense system can deal with a regional heat wave. How does a cell, without eyes and brains, manage to recruit thousands of highly-specialized workers to help their brethren in need? (Did you notice some of the rescuers are called chaperones? Evidently, the same nurses who bring newborn proteins into the world also know how to treat heat stroke.) And to think this is just one of many such systems working simultaneously in the cell to respond to a host of contingencies is truly staggering.
Notice also how the commentators described the heat shock response system as “just what a well trained control engineer would design.” Wonder Who that could be? Tinkerbell? Not with her method of designing (see 03/11/2005 commentary). No matter; leaders in the I.D. movement emphasize that it is not necessary to identify the Designer to detect design. But they also teach that good science requires following the evidence wherever it leads.
You are too kind (now, when I actually do embarrass myself, you'll remember your comments here, right?)
Sure. Hee hee. (Sucked in another one!)
Dobson had an interesting discussion in one of his writings about: revelation, scripture, gut feel; logic.
To those I might add: consultation, group determination, meditation; wisdom; mathematics
These are not rank ordered, but they are all avenues to knowledge or the interpretation thereof.
Please be ready to repost your last, xzins to the new article and please re-ping all the correspondents!
They can be, as PH is busy doing. But the ranking is an added feature. Certainty is not a kind of knowledge
Let's face it. Uncertainty is as certain as anything. Those who ignore that fact generally make for ugly and mean politicians.
This would make an interesting personality test. List all the kinds of knowing and have people rank them. I don't know what it would prove, but I bet it would predict chat room compatibility.
Your attempts to personalize the discussion are doomed to failure. What I believe is irrelevant to a philosphical discussion of what we know and how we know it. To limit, "all that there is" to my own understanding is to commit the very form of arrogance that I object to.
I look at the soundwaves in the CMB and see sound existing long before any biological life and therefore utterly disagree with you
If you accept physical evidence of those soundwaves, however long ago they may have been created, then you accept the physical evidence of their existence. All experience is of past events, it is simply a matter of how long ago they took place, a thousandth of a second or a few billion years ago. "Sound" by definition is an experience.
Once again, this is simply sloppy use of the language, or a misunderstanding of the primacy of language. A Rush Limbaugh likes to misquote Rand, "Words mean things." And as Rand said more precisely, "Words have precise meanings."
Thus, when I say, "By definition" I am saying that the word itself describes its own limits which you may not violate simply because it is inconvenient to your personal beliefs.
I previously had thought you were a materialist, a metaphysical naturalist like several other correspondents here who see “all that there is” as that which occurs in nature,
and I was fully prepared today to not respond because of your offensive personalization of the discussion. That you can dismiss a philosophical position because you deem the proponent a "materialist" is indicative of the weakness of your arguments. Denigrating and thereby dismissing people's views by calling them your favorite epithets is no way to conduct a discussion. Your counterpart did the same by saying I "live in a world of my own personal preferences" never considering how offensive this might be.
If I were to respond in like kind I would then be attacked for attacking you personally, so I can't win no matter what I do. I least I don't have a big beam sticking out of my eye.
Then when you said to betty boop ”There is no such separation between spirit and 4D space/time, can't be tested, can't be proven. “ I took it that your definition of “all that there is” is that which can be (logically) proven, i.e. can’t be proven therefore it doesn’t exist.
This statement proves how poorly versed in logic you are. The Fallacy of Can't Prove a Negative addresses precisely this point. The definition of "all that exists" and "all that has been proven to exist" are two completely different things. Just because something can't be proven to exist doesn't mean it doesn't, logically. Sub-mesons existed before they were "proven" to exist.
On the other hand, just asserting something exists doesn't mean that it does. The question is: Do you have any "evidence" that it exists?
Now, if you want to assert that your subjective experiences qualify as evidence that whatever you claim exists, actually exists; then you have to accept the same claim from anyone else who has a purely "subjective" experience as being just as valid.
This means that every Hindu, Taoist, Zen Buddhist, Muslim, Pagan, Native American and every other belief system you can think of and name has just as much validity as you do.
Until you clarify your view of reality any further discussion of your other comments is pointless.
My view of reality is that it cannot be qualified in any manner, way, shape or form. We simply do not know enough to say what it isn't but only define the tiny corner we have actually discovered and verified. This includes all of the "things" you define as being outside of "all that there is" or this "space/time." You simply cannot know that any of these things actually stand outside of space/time (thus refuting Platonic Philosophical Realism) or that space/time is actually limited or qualified in any way. Until we know everything there is to know about the Universe (in this space/time) nothing can be ruled out.
It is you who are presuming to have knowledge that you simply cannot have, and judging me because I don't see how you can arrive at such a conclusion. Thus your attempt to personalize the discussion.
Sound is a series of mechanical compressions and rarefactions or longitudinal waves that successively propagate through materials (medium) that are at least a little compressible (solid, liquid or gas but not vacuum). In sound waves parts of matter (molecules or groups of molecules) move in a direction of the spreading of the disturbance (as opposite to transversal waves). The cause of sound waves is called the source of waves, e.g. a violin string vibrating upon being bowed or plucked.
A sound wave is usually represented graphically by a wavy, horizontal line; the upper part of the wave (the crest) indicates a compression and the lower part (the trough) indicates a rarefaction.
The perception of sound is the sense of hearing. In humans and many animals this is accomplished by the ears, but loud sounds and low frequency sounds can be perceived by other parts of the body through the sense of touch. Sounds are used in several ways, most notably for communication through speech or, for example, music. Sound perception can also be used for acquiring information about the surrounding environment in properties such as spatial characteristics and presence of other animals or objects. For example, bats use one sort of echolocation, ships and submarines use sonar, and humans can determine spatial information by the way in which they perceive sounds.
The study of sound is called acoustics and is performed by acousticians. A notable subset is psychoacoustics, which combines acoustics and psychology to study how people react to sounds.
For instance, the statement above "that you simply cannot have" is wrongful. That is not a reflection on you but on the statement itself as follows:
One the one hand you assert that space/time reality is entirely subjective and on the other hand you want to have an "objective" definition of the word, "sound." So which is it?
My unabridged Webster's first entry for sound is:
The sensation produced by stimulation of the organs of hearing by vibration transmitted through the air or other medium.
This is the meaning of the Zen Koan: If a tree falls in the forest and there is no one to hear it, is there sound?
Vibration happens, sound IS a perception. To which I would say:
The frequency range of sound audible to humans is approximately between 20 and 20,000 Hz.
is the working definition of sound. The frequency range of vibration between 20 and 20,000 Hz is perceived as sound for human beings. Saying it is "sound" Begs the Question that it is perceived vibration.
What you illustrate here is why there is so much confusion in the world on these issues. The perception of vibration as sound existed long, long before any of these technical definitions.
The definition of sound as "a series of mechanical compressions and rarefactions or longitudinal waves that successively propagate through materials (medium) that are at least a little compressible (solid, liquid or gas but not vacuum)." is relative to space/time. It couldn't exist without space/time. But that definition is not a subjective statement; OTOH, it is not "objective truth" either because we don't know what sound "is" from "beyond" space/time. Max Tegmark, for instance, would suggest that sound is a mathematical structure "beyond" space/time which manifests "in" space/time - but we, from within space/time, cannot know that is the "objective truth" of the matter.
Public release date: 10-Apr-2005
Contact: David Reid
david.reid@iop.org
44-207-470-4815
Institute of Physics
http://www.eurekalert.org/bysubject/mathematics.php
Sacred constant might be changing
Scientists discover one of the constants of the universe might not be constant
Physical constants are one of the cornerstones of physics ? sacred numbers which we know to be fixed ? but what if some of these constants are changing? Speaking at the Institute of Physics conference Physics 2005, Dr Michael Murphy of Cambridge University will discuss the "fine structure constant" ? one of the critical numbers in the universe which seems to be precisely tuned for life to exist ? and suggest that it might not be constant after all.
Dr Murphy has used the largest optical telescope in the world, the Keck telescope on Mauna Kea in Hawaii, to study light from distant quasars. This light has been travelling across the universe for billions of years, and seems to show that the fine structure constant, often known as "alpha", may be varying over time.
The fine structure constant governs the electromagnetic force which holds all atoms and molecules together. Scientists have known for many years that if its value was slightly different, life could not exist. Only the very tiniest changes over time could be tolerated, and most scientists believe that alpha today is the same as it always has been.
The constant also affects the absorption fingerprint of atoms, which can be detected when light shines through gas clouds. Murphy has used quasars as incredibly distant light sources, whose light encounters gas clouds on its way to Earth. The light takes time to reach Earth, so he sees the fingerprints as they were billions of years ago. By comparing these fingerprints with those obtained in experiments on Earth, he concludes that alpha has changed by about one part in two-hundred-thousand during the last 10 billion years.
Other researchers have published results which suggest that alpha does not change. However Dr Murphy's work is the most detailed survey ever performed. He says that the internal checks in his method, which other research groups did not use, make this the most reliable measurement to date.
Murphy is careful not to claim that the case is closed, and he says that nobody can really say that alpha varies until another type of experiment has confirmed it. "We are claiming something extraordinary here," says Murphy, "and the evidence, though strong, is not yet extraordinary enough."
Dr Michael Murphy is a Research Associate at the Institute of Astronomy in the University of Cambridge, and a Research Fellow of Darwin College, Cambridge.
###
Contact Details: Dr Michael Murphy, Tel: 0122-333-7505, Email: mim@ast.cam.ac.uk
Michael Murphy's research website: http://www.ast.cam.ac.uk/~mim/res.html
Dr Murphy is available for interviews: Contact David Reid, Institute of Physics, 44-207-470-4815 to arrange an interview.
I had an interesting look at this sort of "relative" thing today, while doing a bit of orbitology. Specifically, I was playing around with differences between a couple of satellite trajectories. The normal approach is to look at the differences as a function of time, and I saw pretty much what I expected -- an oscillation in the position differences that grew with time.
However, I also had reason to believe that the three position differences had a "phase" relationship -- and so I plotted the component differences against each other. Along-track vs. radial differences formed a rather interesting spiral, as did along-track vs. crosstrack position differences. Radial vs. cross-track was obviously a tilted "side view" of a yet another spiral. What I saw as oscillations in the "position vs. time" plots was nothing more than a cross-sectional slice of a motion for which there was more than simply a time-dependence in the motion -- the actual motion was more complex than the position vs. time plots could show.
The point here is that your "relative to space/time" statements are very much like this -- perhaps what we see in 4D is likewise a cross-sectional "slice" of motion within a larger-dimensioned universe?
This is not of necessity, as I understand it, but rather because the belief is we ought to "notice" a higher dimension. That has always bothered me since our vision and minds are restricted to what appears to be four (seemingly arbitrary) dimensions out of n.
There's also the Randall theory that gravity is so small compared to the other fields because it is interdimensional. Branification: An alternative to compactification.
As you can see, there are theories for higher dimensional dynamics, as you suggest - and they are state-of-the-art. Below is one group I've been watching for quite a long time because they have doggedly avoided the compactification model. You might find their work interesting also:
Welcome to the homepage of the 5D Space-Time-Matter consortium. We are a group of physicists and astronomers working on a five-dimensional version of general relativity. Our work differs from Kaluza-Klein theory (the basis of superstrings) in that we do not assume compactification of the extra dimension. This means that new terms (those involving the 5th coordinate) enter into physics, even at low energies. In 4D spacetime these can be interpreted as matter and energy. We move them to the right-hand side of the 4D field equations and take them to describe an induced energy-momentum tensor. In fact, we have shown that no 5D energy-momentum tensor is required. 4D matter of all kinds can arise as a manifestation of a higher-dimensional vacuum. This is one way to realize Einstein's dream of transmuting the "base wood" of matter into the "pure marble" of geometry -- that is, of unifying the gravitational field, not just with other fields but with its source.
Fascinating post, ckilmer! This development bears watching. Thank you so much for the post/ping!
Perhaps there's even a connection -- maybe that 5th dimension has some correspondence to an "imaginary" time axis, as opposed to the "real" time we experience.
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