Friday, June 11, 2010

The Gibbs Paradox

Last week in this blog, I wrote that the “Gibbs Paradox” deserved an entire entry of its own. Well, here it is. Russ Hobbie and I mention the Gibbs Paradox in a footnote in Section 3.18 (The Chemical Potential of a Solution) in the 4th edition of Intermediate Physics for Medicine and Biology. When calculating the entropy of mixing (where a solute and solvent are intermixed), we derived an expression for the number of ways N particles can be distributed among N sites. If we assume the solute particles are indistinguishable, there is only one way. The footnote then reads
The fact that there is only one mircostate because of the indistinguishability of the particles is called the Gibbs paradox. For an illuminating discussion of the Gibbs paradox, see Casper and Freier (1973).
Fundamentals of Statistical and Thermal Physics, by Frederick Reif, superimposed on Intermediate Physisc for Medicine and Biology.
Fundamentals of Statistical
and Thermal Physics,
by Frederick Reif.
The Gibbs Paradox is examined in more detail by Frederick Reif in his landmark textbook Fundamentals of Statistical and Thermal Physics. (Indeed, Chapter 3 of Intermediate Physics for Medicine and Biology follows a statistical approach similar to Reif’s analysis, and even more similar to the discussion in his introductory textbook—a personal favorite of mine—Statistical Physics, Berkeley Physics Course Volume 5). Reif considers “a gas consisting of N identical monatomic molecules of mass m enclosed in a container of volume V.” When he calculates the entropy, S, of the gas, he obtains
S = N k [ln V + 3/2 ln T + σ]     (7.2.16)
where k is Boltzmann’s constant, T is the absolute temperature, and σ is a constant independent of N, T, and V. He then ends the section with the provocative statement “This expression for the entropy is, however, not correct,” which leads to his discussion (Sec. 7.3) of the Gibbs paradox. Reif continues
The challenging statement at the end of the last section suggests that the expression (7.2.16) for the entropy merits some discussion… [The expression] for S is clearly wrong since it implies that the entropy does not behave properly as an extensive quantity. Quite generally, one must require that all thermodynamic relations remain valid if the size of the whole system under consideration is simply increased by a scale factor α, i.e., if all its extensive parameters are multiplied by the same factor α. In our case, if the independent extensive parameters V and N are multiplied by α, the mean energy… is indeed properly increased by this same factor, but the entropy S in (7.2.16) is not increased by α because of the term N ln V.

Indeed, (7.2.16) asserts that the entropy S of a fixed volume V of gas is simply proportional to the number N of molecules. But this dependence on N is not correct, as can readily be seen in the following way. Imagine that a partition is introduced which divides the container into two parts. This is a reversible process which does not affect the distribution of systems over accessible states. Thus, the total entropy ought to be the same with, or without, the partition in place; i.e.

S = S' + S"     (7.3.1)

where S' and S" are the entropies of the two parts. But the expression (7.2.16) does not yield the simple additivity required by (7.3.1). This is easily verified. Suppose, for example, that the partition divides the gas into two equal parts, each containing N' molecules of gas in a volume V'. Then the entropy of each part is given by (7.2.16) as

S' = S" = N' k [ln V' + 3/2 ln T + σ]

while the entropy of the whole gas without partition is by (7.2.16)

S = 2 N' k [ ln (2 V') + 3/2 ln T + σ] .

Hence

S – 2 S' = 2 N' k ln(2 V') – 2 N' k ln V' = 2 N' k ln2

and is not equal to zero as required by (7.3.1).

This paradox was first discussed by Gibbs and is commonly referred to as the “Gibbs paradox.” Something is obviously wrong in our discussion; the question is what.
Reif then analyzes in more detail the implications of removing the partition between the two sides of the box. He finds that
The act of removing the partition has thus very definite physical consequences. Whereas before removal of the partition a molecule of each subsystem could only be found within a volume V', after the partition is removed it can be located anywhere within the volume V = 2 V'. If the two subsystems consisted of different gasses, the act of removing the partition would lead to diffusion of the molecules throughout the whole volume 2V' and consequent random mixing of the different molecules. This is clearly an irreversible process; simply replacing the partition would not unmix the gases. In this case the increase in entropy in (7.3.2) would make sense as being simply a measure of the irreversible increase of disorder resulting from the mixing of unlike gases [the entropy of mixing that Russ and I calculated].

But if the gases in the subsystems are identical, such an increase of entropy does not make physical sense. The root of the difficulty embodied in the Gibbs paradox is that we treated the gas molecules as individually distinguishable, as though interchanging the positions of two like molecules would lead to a physically distinct state of the gas. This is not so. Indeed, if we treated the gas by quantum mechanics (as we shall do in Chapter 9), the molecules would, as a matter of principle, have to be regarded as completely indistinguishable. A calculation of the partition function would then automatically yield the correct result, and the Gibbs paradox would never arise. Our mistake has been to take the classical point of view too seriously. Even though one may be in a temperature and density range where the motion of molecules can be treated to a very good approximation by classical mechanics, one cannot go so far as to disregard the essential indistinguishability of the molecules.
In a sidenote, Reif adds
Just how different must molecules be before they should be considered distinguishable?… In a classical view of nature two molecules could, or course, differ by infinitesimal amounts… In a quantum description this troublesome question does not arise because of the quantized discreteness of nature… Hence the distinction between identical and nonidentical molecules is completely unambiguous in a quantum-mechanical description. The Gibbs paradox thus foreshadowed already in the last [19th] century conceptual difficulties that were resolved satisfactorily only by the advent of quantum mechanics.
Several good American Journal of Physics articles discuss the Gibbs phenomenon. Pesic examines Gibb’s own writings to trace his thoughts on the issue (“The Principle of Identicality and the Foundations of Quantum Theory: I. The Gibbs Paradox,” American Journal of Physics, Volume 59, Pages 971–974, 1991), and Landsberg and Tranah study in more detail in role of the Gibbs paradox for quantum mechanics (“The Gibbs Paradox and Quantum Gases,” American Journal of Physics, Volume 46, Pages 228–230, 1978). Finally, Casper and Freier (the authors of the paper cited in our footnote) analyze the Gibbs paradox by comparing macroscopic and microscopic points of view (“‘Gibbs Paradox’ Paradox,” American Journal of Physics, Volume 41, Pages 509–511, 1973).

You know, there is a lot of physics in that little footnote on page 68 of Intermediate Physics for Medicine and Biology.

Friday, June 4, 2010

The Gibbs Phenomenon

In chapter 11 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss Fourier analysis, a fascinating but very mathematical subject. One of the most surprising results of Fourier analysis is the Gibbs phenomenon, which we describe at the end of Sec. 11.5 (Fourier Series for a Periodic Function).
Table 11.4 shows the first few coefficients for the Fourier series representing the square wave, obtained from Eq. 11.34… Figure 11.16 shows the fits for n = 3 and n = 39. As the number of terms in the fit is increased, the value of Q [measuring the least squares fit between the function at its Fourier series] decreases. However, spikes of constant height (about 18% of the amplitude of the square wave or 9% of the discontinuity in y) remain. These are seen in Fig. 11.16. These spikes appear whenever there is a discontinuity in y and are called the Gibbs phenomenon.
You have to be amazed by the Gibbs phenomenon. Think about it: as you add terms in the sum, the fit between the function and its Fourier series gets better and better, but the overshoot in amplitude does not get any smaller. Instead, the region containing ringing near the discontinuity gets narrower and narrower. If you want to see a figure like our Fig. 11.16 presented as a neat animation, take a look at http://www.sosmath.com/fourier/fourier3/gibbs.html. Also, check out http://ocw.mit.edu/ans7870/18/18.06/javademo/Gibbs/ for an interactive demo that will let you include up to 200 terms in the Fourier series.

The Gibbs phenomenon is important in medical imaging. The entry for the Gibbs phenomenon from the Encyclopedia of Medical Imaging is reproduced below.
Gibbs phenomenon, (J. Willard Gibbs, 1839-1903, American physicist), phenomenon occurring whenever a “curve” with sharp edges is subject to Fourier analysis. The Gibbs phenomenon is relevant in MR imaging, where it is responsible for so-called Gibbs artefacts. Consider a signal intensity profile across the skull, where at the edge of the brain the signal intensity changes from virtually zero to a finite value. In MR imaging the measurement process is a breakdown of such intensity profiles into their Fourier harmonics. i.e. sine and cosine functions. Representation of the profiles measured with a limited number of Fourier harmonics is imperfect, resulting in high frequency oscillations at the edges, and the image can therefore exhibit some noticeable signal intensity variations at intensity boundaries: the Gibbs phenomenon, overshoot artefacts, or “ringing.” The artefacts can be suppressed by filtering the images. However, filtering can in turn reduce spatial resolution.
Figures 12.24 and 12.25 of our book show a CT scan with ringing inside the skull and its removal by filtering, an example of the Gibbs phenomenon.

Josiah Willard Gibbs was a leading American physicist from the 19th century. He is particularly well known for his contributions to thermodynamics. Gibbs appears at several places in Intermediate Physics for Medicine and Biology. Section 3.17 discusses the Gibbs free energy, a quantity that provides a simple way to keep track of the changes in total entropy when a system is in contact with a reservoir at constant temperature and pressure. A footnote on page 68 addresses the Gibbs paradox (which deserves an entire blog entry of its own), and Problem 47 in Chapter 3 introduces the Gibbs factor (similar to the Boltzmann factor but including the chemical potential).

Selected Papers of Great American Physicists, superimposed on Intermediate Physics for Medicine and Biology.
Selected Papers of Great
American Physicists.
The preface to Gibbs’ book on statistical mechanics is reproduced in Selected Papers of Great American Physicists: The Bicentennial Commemorative Volume of the American Physical Society 1976, edited by Spencer Weart. I recall being quite impressed by this book when in graduate school at Vanderbilt University. Below is a quote from Weart’s biographical notes about Gibbs.
Gibbs, son of a Yale professor of sacred literature, descended from a long line of New England college graduates. He studied at Yale, received his Ph.D. there in 1863—one of the first doctorates granted in the United States—tutored Latin and natural philosophy there, and then left for three decisive years in Europe. Up to that time, Gibbs had shown interest in both mathematics and engineering, which he combined in his dissertation “On the Form of the Teeth in Wheels in Spur Gearing.” The lectures he attended in Paris, Berlin and Heidelberg, given by some of the greatest men of the day, changed him once and for all. In 1871, two years after his return from Europe, he became Yale’s first Professor of Mathematical Physics. He had not yet published any papers on this subject. For nine years he held the position without pay, living on the comfortable inheritance his father had left; only when Johns Hopkins University offered Gibbs a post did Yale give him a small salary.

Gibbs never married. He lived out a calm and uneventful life in the house where he grew up, which he shared with his sisters. He was a gentle and considerate man, well-liked by those who knew him, but he tended to avoid society and was little known even in New Haven. Nor was he known to more than a few of the world’s scientists—partly because his writings were extremely compact, abstract and difficult. As one of Gibb’s European colleagues wrote, “Having once condensed a truth into a concise and very general formula, he would not think of churning out the endless succession of specific cases that were implied by the general proposition; his intelligence, like his character, was of a retiring disposition.” The Europeans paid for their failure to read Gibbs: A large part of the work they did in thermodynamics before the turn of the century could have been found already in his published work.

Friday, May 28, 2010

Happy Birthday Laser!

Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles, by Eisberg and Resnick, superimposed on Intermediate Physics for Medicine and Biology.
Quantum Physics of Atoms,
Molecules, Solids, Nuclei, and Particles,
by Eisberg and Resnick.
This month marks the 50th anniversary of the invention of the laser. In May 1960, Theodore Maiman built the first device to produce coherent light by the mechanism of “Light Amplification by Stimulated Emission of Radiation” at Hughes Research Laboratories in Malibu, making the laser just slightly older than I am. A special website, called laserfest, is commemorating this landmark event. Eisberg and Resnick discuss lasers in Section 11.7 of their textbook Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles (quoted from the first edition, 1974).
In the solid state laser that operates with a ruby crystal, some Al atoms in the Al2O3 molecules are replaced by Cr atoms. These “impurity” chromium atoms account for the laser action… The level of energy E1 is the ground state and the level of energy E3 is the unstable upper state with a short lifetime (≈10−8 sec), the energy difference E3-E1 corresponding to a wavelength of about 5500 Å. Level E2 is an intermediate excited state which is metastable, its lifetime against spontaneous decay being about 3 x 10−3 sec. If the chromium atoms are in thermal equilibrium, the population number of the states are such that [n3 is less than n2 is less than n1]. By pumping in radiation of wavelength 5500 Å, however, we stimulate absorption of incoming photons by Cr atoms in the ground state, thereby raising the population number of energy state E3 and depleting energy state E1 of occupants. Spontaneous emission, bringing atoms from state 3 to state 2, then enhances the occupancy of state 2, which is relatively long-lived. The result of this optical pumping is to decrease n1 and increase n2, such that n2 is greater than n1 and population inversion exists. Now, when an atom does make a transition from state 2 to state 1, the emitted photon of wavelength 6943 Å will stimulate further transitions. Stimulated emission will dominate stimulated absorption (because n2 is greater than n1) and the output of photons of wavelength 6943 Å is much enhanced. We obtain an intensified coherent monochromatic beam.
Lasers are an important tool in biology and medicine. Russ Hobbie and I discuss their applications in Chapter 14 (Atoms and Light) the 4th edition of Intermediate Physics for Medicine and Biology. In Section 14.5 (The Diffusion Approximation to Photon Transport) we write
A technique made possible by ultrashort light pulses from a laser is time-dependent diffusion. It allows determination of both μs and μa [the scattering and absorption attenuation coefficients]. A very short (150-ps) pulse of light strikes a small region on the surface of the tissue. A detector placed on the surface about 4 cm away records the multiply-scattered photons… A related technique is to apply a continuous laser beam, the amplitude for which is modulated at various frequencies between 50 and 800 MHz. The Fourier transform of Eq. 14.29 gives the change in amplitude and phase of the detected signal. Their variation with frequency can also be used to determine μa and μs.
We also mention lasers in Section 14.10 (Heating Tissue with Light).
Sometimes tissue is irradiated in order to heat it; in other cases tissue heating is an undesired side effect of irradiation. In either case, we need to understand how the temperature changes result from the irradiation. Examples of intentional heating are hyperthermia (heating of tissue as a part of cancer therapy) or laser surgery (tissue ablation). Tissue is ablated when sufficient energy is deposited to vaporize the tissue.
Russ and I give many references about lasers in medicine in our Resource Letter (“Resource Letter MP-2: Medical Physics,” American Journal of Physics, Volume 77, Pages 967–978, 2009):
F. Lasers and optics

Lasers have introduced many medical applications of light, from infrared to the visible spectrum to ultraviolet.

150. Lasers in Medicine, edited by R. W. Waynant (CRC, Boca Raton, 2002). (I)

151. Laser-Tissue Interactions: Fundamentals and Applications, M. H. Niemz (Springer, Berlin, 2007). (I)

152. “Lasers in medicine,” Q. Peng, A. Juzeniene, J. Chen, L. O. Svaasand, T. Warloe, K.-E. Giercksky, and J. Moan, Rep. Prog. Phys. 71, Article 056701, 28 pages
(2008). (A)

A fascinating and fast-growing new technique to image biological tissue is optical coherence tomography “OCT.” It uses reflections like ultrasound but detects the reflected rays using interferometry.

153. Optical Coherence Tomography, M. E. Brezinski (Elsevier, Amsterdam, 2006). Overview of the physics of OCT and applications to cardiovascular medicine, musculoskeletal disease, and oncology. (I)

154. “Optical coherence tomography: Principles and applications,” A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, Rep. Prog. Phys. 66, 239–303 (2003). (I)

With infrared light, scattering dominates over absorption. In this case, light diffuses through the tissue. Optical imaging in turbid media is difficult but not impossible.

155. “Recent advances in diffuse optical imaging,” A. P. Gibson, J. C. Hebden, and S. R. Arridge, Phys. Med. Biol. 50, R1–R43 (2005). (I)

156. “Pulse oximetry,” R. C. N. McMorrow and M. G. Mythen, Current Opinion in Critical Care 12, 269–271 (2006). The pulse oximeter measures the oxygenation of blood and is based on the diffusion of infrared light. (I)

One impetus for medical applications of light has been the development of new light sources, such as free-electron lasers and synchrotrons. In both cases, the light frequency is tunable over a wide range.

157. “Free-electron-laser-based biophysical and biomedical instrumentation,” G. S. Edwards, R. H. Austin, F. E. Carroll, M. L. Copeland, M. E. Couprie, W. E. Gabella, R. F. Haglund, B. A. Hooper, M. S. Hutson, E. D. Jansen, K. M. Joos, D. P. Kiehart, I. Lindau, J. Miao, H. S. Pratisto, J. H. Shen, Y. Tokutake, A. F. G. van der Meer, and A. Xie, Rev. Sci. Instrum. 74, 3207–3245 (2003). (I)

158. “Medical applications of synchrotron radiation,” P. Suortti and W. Thomlinson, Phys. Med. Biol. 48, R1– R35 (2003). (I)

Finally, photodynamic therapy uses light-activated drugs to treat diseases.

159. “The physics, biophysics and technology of photodynamic therapy,” B. C. Wilson and M. S. Patterson, Phys. Med. Biol. 53, R61–R109 (2008). (A)
Happy birthday, laser!

Friday, May 21, 2010

Kalin Lucas and his ruptured Achilles tendon

Basketball fans may recall that in this year's NCAA tournament, Michigan State University (located about a 90 minute drive from where I work here at Oakland University in Rochester Michigan) made it into the final four before losing to Butler. They might have won the entire tournament if they were not without their star, Kalin Lucus, who ruptured his left Achilles tendon in a second round game against the University of Maryland. Coach Tom Izzo, who is much beloved here in southeast Michigan, managed two more wins without Lucus, before losing in the semifinals.

Why did Lucus injure his Achilles tendon? There was no collision or accident, he just landed awkwardly. Readers of the 4th edition of Intermediate Physics for Medicine and Biology won’t be too surprised when they hear about sports injuries to the Achilles tendon. In Section 1.5 of our book, Russ Hobbie and I analyze the forces on the Achilles tendon and show that the tension in this tendon can be nearly twice the body weight.
The Achilles tendon connects the calf muscles (the gastrocnemius and soleus) to the calcaneus at the back of the heal (Fig. 1.9). To calculate the force exerted by this tendon on the calcaneus when a person is standing on the ball of one foot, assume that the entire foot can be regarded as a rigid body. This is our first example of creating a model of the actual situation. We try to simplify the real situation to make the calculation possible while keeping the features that are important to what is happening. In this model the internal forces within the foot are being ignored.

Figure 1.10 shows the force exerted by the tendon on the foot (FT), the force of the leg bones (tibia and fibula) on the foot (FB), and the force of the floor upward, which is equal to the weight of the body (W)...
We then go one to solve the equations of translational and rotational equilibrium to find that FT = 1.8 W and FB = 2.8 W, and conclude
The tension in the Achilles tendon is nearly twice the person’s weight, while the force exerted on the leg by the talus is nearly three times the body weight. Once can understand why the tendon might rupture.
Many sports injuries result from the laws of biomechanics. The problem is often that a tendon must exert a large force in order to create enough torque to maintain rotational equilibrium. For the Achilles tendon, the moment arm between the joint and the tendon is roughly half the moment arm between the joint and the ball of the foot, so the force on the tendon must be about twice the weight. Our bodies are often built this way: large forces are required to make up for small moment arms. I sometimes give a problem on one of my Biological Physics (PHY 325) exams that illustrates this by calculating the forces on the shoulder of a gymnast performing an “iron cross” on the rings. Here again, the torque exerted by the rings on the arm is huge because of the large moment arm (essentially the entire length of the arm itself), while the moment arm of the pectoral muscle is small because it connects to the humerus (the arm bone) only about 5 cm from the shoulder, at a small angle. The problem suggests that the pectoral muscle must supply a force of over twenty times the body weight! No wonder I was so poor at the rings in my high school physical education class. Readers interested in learning more about this topic might want to read Williams and Lissner's classic textbook Biomechanics of Human Motion. Russ and I cite the 1962 first edition, but I believe that the book has evolved into Biomechanics of Human Motion: Basics and Beyond for the Health Professions, by Barney LeVeau, due out later this year.

Hopefully these insights into biomechanics can help you appreciate how Kalin Lucus could suffer a season-ending injury so easily. I’m glad MSU was able to make it to the final four even without Lucus. However, to be honest, the Spartans were only my 4th favorite team in the tournament this year. Oakland University participated in March Madness for only the second time in the school’s history. Vanderbilt University (where I went for graduate school) also reached the Big Dance, and many predicted that the University of Kansas (where I attended college) would win the entire event. Unfortunately, all three schools lost in the first weekend of play. Russ didn’t fare much better, as the University of Minnesota lost in the first round. Congratulations to Duke University (home to an excellent Biomedical Engineering Department) for their ultimate victory.

Friday, May 14, 2010

Single-Pool Exponential Decomposition Models: Potential Pitfalls in their Use in Ecology Studies

In Section 11.2 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss fitting data using nonlinear least squares. Our first example in this section is a fit using a single exponential decay, y(x) = a e–bx, where a and b are to be determined. We suggest that the reader
“take logarithms of each side of the equation

log y = log ab x log e

v = a' – b' x.

This can be fit by the linear [least squares] equation, determining constants a' and b' using Eqs. 11.5.”
This method works fine for ideal data, but in almost any real application the data will be corrupted by noise. In that case, fitting a linear equation to the logarithm of the data may not be wise. I discussed this issue last year in the May 22 entry to this blog, but wish to explore it in more detail this week.

Recently, Russ coauthored a paper about his recent results on this topic, published in the journal Ecology (Volume 91, Pages 1225–1236). In collaboration with his daughter Sarah Hobbie (Associate Professor in the Department of Ecology, Evolution and Behavior at the University of Minnesota), and her former postdoc E. Carol Adair (currently with the National Center for Ecological Analysis and Synthesis at the University of California Santa Barbara), Russ examined “Single-Pool Exponential Decomposition Models: Potential Pitfalls in their Use in Ecology Studies.” The abstract to the paper is given below.
The importance of litter decomposition to carbon and nutrient cycling has motivated substantial research. Commonly, researchers fit a single-pool negative exponential model to data to estimate a decomposition rate (k). We review recent decomposition research, use data simulations, and analyze real data to show that this practice has several potential pitfalls. Specifically, two common decisions regarding model form (how to model initial mass) and data transformation (log-transformed vs. untransformed data) can lead to erroneous estimates of k. Allowing initial mass to differ from its true, measured value resulted in substantial over- or underestimation of k. Log-transforming data to estimate k using linear regression led to inaccurate estimates unless errors were lognormally distributed, while nonlinear regression of untransformed data accurately estimated k regardless of error structure. Therefore, we recommend fixing initial mass at the measured value and estimating k with nonlinear regression (untransformed data) unless errors are demonstrably lognormal. If data are log-transformed for linear regression, zero values should be treated as missing data; replacing zero values with an arbitrarily small value yielded poor k estimates. These recommendations will lead to more accurate k estimates and allow cross-study comparison of k values, increasing understanding of this important ecosystem process.
The authors performed a massive review of the literature, reading and analyzing nearly 500 papers about litter decomposition, most of which fit data to an exponential decay, e–kt. The bottom line is that doing a linear least squares fit to the logarithm of the data can cause significant errors. Much better is to use a nonlinear least squares fit. The manuscript concludes “We suggest that careful selection of fitting methods, as we have described above, will lead to more accurate and comparable k estimates, thereby increasing our understanding of this important ecosystem process.” Of course, my favorite thing about their paper is that it cites the 4th edition of Intermediate Physics for Medicine and Biology!

One pitfall can be illustrated by considering measurements of the voltage across a resistor in an RC circuit. The voltage decays with an RC time constant. However thermal, or Johnson, noise is also present (see Section 9.8). Once the voltage decays to less than the Johnson noise, the measured voltage fluctuates between positive and negative values. If you take the logarithm of the voltage, the negative values are undefined. In other words, you can’t do a linear least squares fit to the logarithm of the data if the data can be negative. The problem remains even when the data is nonnegative (as in Hobbie’s paper) if the data can be zero. However, if you make a nonlinear least squares fit of the data itself (rather than the logarithm of the data) the problem vanishes.

In order to explain these observations in Intermediate Physics for Medicine and Biology, Russ and I (mainly Russ) wrote an Addendum available at the book’s website. It lists what changes are needed to properly explain least squares fitting of exponential data. Enjoy!

Friday, May 7, 2010

Hysteresis and Bistability in the Direct Transition from 1:1 to 2:1 Rhythm in Periodically Driven Single Ventricular Cells

When preparing the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I added two homework problems (Problems 37 and 38) in Chapter 10 (Feedback and Control) about “cardiac restitution.” These problems contain a fascinating and elegantly simple example of restitution that provides insight into nonlinear dynamics and chaos. Problem 37 begins
Problem 37 The onset of ventricular fibrillation in the heart can be understood in part as a property of cardiac restitution.” The action potential duration (APD) depends on the previous diastolic interval (DI): the time from the end of the last action potential until the start of the next one. The relationship between APD and DI is called the restitution curve. In cardiac muscle, a typical restitution curve has the form

APDi+1 = 300 (1 – exp(DIi/100))

where all times are given in ms. Suppose we apply to the heart a series of stimuli, with period (or cycle length) CL. Since APD + DI = CL, we have DIi+1 = CL – APDi+1.
The problem then goes on to have the reader do some numerical calculations using various cycle lengths and initial diastolic intervals. Depending on the parameters, you can get (a) a simple 1:1 response between stimulation and action potential, (b) a 2:2 response in which every stimulus triggers an action potential but the APD alternates between long and short, a behavior called “alternans,” (c) a 2:1 response where an action potential is triggered by every second stimulus, with the tissue being refractory and not responding to the other stimuli, and (d) chaos. I have found this model is an excellent way to introduce students to chaotic behavior; even students with a weak mathematics background can understand it. When discussing this mathematical model with students, I often hand out a particularly clear paper to serve as background reading: J. N. Weiss, A. Garfinkel, H. S. Karagueuzian, Z. Qu, and P.-S. Chen (1999) “Chaos and the Transition to Ventricular Fibrillation: A New Approach to Antiarrhythmic Drug Evaluation,” Circulation, Volume 99, Pages 2819–2826.

Problem 38 explores how to understand this behavior by analyzing the slope of the restitution curve. If the slope is too steep, the behavior becomes more complex. Part (d) of Problem 38 says
Suppose you apply a drug to the heart that can change the restitution curve to

APDi+1 = 300 (1 – b exp(DIi/100)) .

Plot APD as a function of DI for b = 0, 0.5, and 1. What value of b ensures that the slope of the restitution curve is always less than 1? Garfinkel et al. (2000) have suggested that one way to prevent ventricular fibrillation is to use drugs to flatten the restitution curve.
There is yet another type of behavior that is not discussed in Problems 37 or 38: a bistable response. Below is a new homework problem that discusses bistable behavior.
Problem 38 ½ Use the restitution curve from Problem 38, with b = 1/3 and CL = 250, to analyze the response of the system with initial diastolic intervals of 50, 60, 70, 80, and 90. You should find that the qualitative behavior depends on the initial condition. Which values of the initial diastolic interval give a 1:1 response, and which give 2:1? Determine the initial value of the DI, to three significant figures, for which the system makes a transition from one behavior to the other. When two qualitatively different behaviors can both occur, depending on the initial conditions, the system is “bistable.” To learn more about such behavior, see Yehia et al. (1999).
The full citation to the paper mentioned at the end of the problem is
Yehia, A. R., D. Jeandupeux, F. Alonso, and M. R. Guevara (1999) “Hysteresis and Bistability in the Direct Transition From 1:1 to 2:1 Rhythm in Periodically Driven Single Ventricular Cells,” Chaos, Volume 9, Pages 916–931.
The senior author on this article is Michael Guevara, of the Centre for Applied Mathematics in Bioscience and Medicine at McGill University. The introductory paragraph of their paper is reproduced below.
The majority of cells in the heart are not spontaneously active. Instead, these cells are excitable, being driven into activity by periodic stimulation originating in a specialized pacemaker region of the heart containing spontaneously active cells. This pacemaker region normally imposes a 1:1 rhythm on the intrinsically quiescent cells. However, the 1:1 response can be lost when the excitability of the paced cells is decreased, when there are problems in the conduction of electrical activity from cell to cell, or when the heart rate is raised. When 1:1 synchronization is lost in the intact heart, one of a variety of abnormal cardiac arrhythmias can arise. In single quiescent cells isolated from ventricular muscle, 1:1 rhythm can be replaced by a N+1:N rhythm (N≥2), a period-doubled 2:2 rhythm, or a 2:1 rhythm. We investigate below the direct transition from 1:1 to 2:1 rhythm in experiments on single cells and in numerical simulations of an ionic model of a single cell formulated as a nonlinear system of differential equations. We show that there is hysteresis associated with this transition in both model and experiment, and develop a theory for the bistability underlying this hysteresis that involves the coexistence of two stable fixed-points on a two-branched one-dimensional map.
For those interested in exploring the application of nonlinear dynamics to biology and medicine in more detail, two books Russ and I cite in Intermediate Physics for Medicine and Biology—and which I recommend highly—are From Clocks to Chaos by Leon Glass and Michael Mackey (both also at McGill) and Nonlinear Dynamics and Chaos by Steven Strogatz.

Friday, April 30, 2010

Max Planck and Blackbody Radiation

Max Planck is one of the founders of quantum mechanics, and the fundamental constant governing all quantum phenomena bears his name. His historic contribution arose from the study of thermal radiation. Section 14.7 in the 4th edition of Intermediate Physics for Medicine and Biology analyzes thermal radiation (also known as blackbody radiation), but does not tell the fascinating history behind this advance. In fact, Russ Hobbie and I write “we will not discuss the history of these developments, but will simply summarize the properties of the blackbody radiation function that are important to us.” What better place than this blog to fill in the missing history.

Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles, by Eisberg and Resnick, superimposed on Intermediate Physics for Medicine and Biology.
Quantum Physics of Atoms,
Molecules, Solids, Nuclei, and Particles,
by Eisberg and Resnick.
Eisberg and Resnick’s textbook Quantum Physics of Atoms, Molecules, Solids, Nuclei, and Particles is a good place to learn more (I will quote from the first edition having the silver cover, which I used as an undergraduate). In fact, the opening section of their first chapter addresses this very issue.
At a meeting of the German Physical Society on Dec. 14, 1900, Max Planck read his paper “On the Theory of the Energy Distribution Law of the Normal Spectrum.” This paper, which first attracted little attention, was the start of a revolution in physics. The date of its presentation is considered to be the birthday of quantum physics, although it was not until a quarter century later that modern quantum mechanics, the basis of our present understanding, was developed by Schroedinger and others… Quantum physics represents a generalization of classical physics that includes the classical laws as special cases. Just as relativity extends the range of application of physical laws to the region of high velocities, so quantum physics extends the range to the region of small dimensions; and, just as a universal constant of fundamental significance, the velocity of light c, characterizes relativity, so a universal constant of fundamental significance, now called Planck’s constant h, characterizes quantum physics. It was while trying to explain the observed properties of thermal radiation that Planck introduced this constant in his 1900 paper…
Eisberg and Resnick end their first chapter with “A Bit of Quantum History”
At first Planck was unsure whether his introduction of the constant h was only a mathematical device or a matter of deep physical significance. In a letter to R. W. Wood, Planck called his limited postulate “an act of desperation.” “I knew,” he wrote, “that the problem (of the equilibrium of matter and radiation) is of fundamental significance for physics; I knew the formula that reproduces the energy distribution in the normal spectrum; a theoretical interpretation had to be found at any cost, no matter how high.”
To better understand the mathematics underlying blackbody radiation, try the new homework problem below, based on Eisberg and Resnick’s analysis (you may want to review Sec. 3.7 of our book about the Boltzmann factor before you attempt this problem).
Section 14.7
Problem 22.5 Let us derive the blackbody spectrum, Eq. 14.37.
(a) Assume the energy En of radiation with frequency ν is discrete, En = h ν n, where n=0, 1, 2, … Let the probability Pn of any state be given by the Boltzmann factor, C e−nhν/kT. Normalize this probability distribution (that is, find C by setting the sum of the probabilities over all states equal to one).
(b) Find the average energy Eave for frequency ν by performing the sum Eave = P0 E0 + P1 E1 + … .
(c) The number of frequencies per unit volume in the frequency range from ν to ν + dν is 8πν2dν/c3. Multiply the result from (b) by this quantity, to get the energy density of the radiation.
(d) The spectrum of power per unit area emitted from a blackbody is equal to c/4 times the energy density. Find the power per unit area per unit frequency, Wν(ν,T) (Eq. 14.37).
You may need to use the following two infinite series
1 + x + x2 + x3 + … = 1/(1−x) ,
x + 2x2 + 3x3 + … = x/(1x)2 .

Friday, April 23, 2010

Therapeutic Touch

Therapeutic touch is a “healing technique” in which a therapist places their hands near a patient and detects or manipulates the patient’s “energy field.” Russ Hobbie and I don’t discuss therapeutic touch in the 4th edition of Intermediate Physics for Medicine and Biology, nor will we include it in future editions. However, since this egregious example of “voodoo science” hasn’t gone away (see http://www.therapeutictouch.org), let me address it here in this blog.

Bob Park described therapeutic touch in his delightful April 3, 1998 entry to his What’s New weekly column.
3. HUMAN ENERGY FIELD: SCIENTIST, AGE 9, TESTS TOUCH THERAPY.
More than 40,000 health professionals have been trained in TT and it's offered by 70 hospitals in the US. And yet no one had ever checked to see if practitioners can, as they claim, tactilely sense such a field—until now. The Journal of the American Medical Association this week published the research of a fourth-grade girl. For a science fair project, the little girl persuaded 21 touch therapists to submit to a beautifully simple test. In 280 trials, the 21 scored 44%. According to the editor of JAMA, reviewers found the study to be “solid gold.” The James Randi Educational Foundation has been offering $1M to anyone who can pass a similar test—only one tried (WN 27 Mar 98) , but a 9-year old must have seemed less threatening. The girl, Emily Rosa of Loveland, CO, now 11, plans to take on magnet therapy next.
Recently, Russ called my attention to Eugenie Mielczarek’s insightful commentary “Magnetic Fields, Health Care, Alternative Medicine and Physics” in the April 2010 edition of Physics and Society, the quarterly newsletter of the Forum of Physics and Society, a division of the American Physical Society. Mielczarek writes
In Therapeutic Touch the protocol requires that a therapist moves his or her hands over the patient’s “energy field,” allegedly “tuning” a purported “aura” of biomagnetic energy that extends above the patient’s body. This is thought to somehow help heal the patient. Although this is less than one percent of the strength of Earth’s magnetic field, corresponds to billions of times less energy than the energy your eye receives when viewing even the brightest star in the night sky, and is billions of times smaller than that needed to affect biochemistry, the web sites of prominent clinics nevertheless market the claims.
Iron, Nature's Universal Element:  Why People Need Iron   and Animals Make Magnets,  by Eugenie Mielczarek, superimposed on Intermediate Physics for Medicine and Biology.
Iron, Nature's Universal Element:
Why People Need Iron
and Animals Make Magnets
,
by Eugenie Mielczarek.
Mielczarek is an emeritus professor at George Mason University. In 2006 she published a Resource Letter in the American Journal of Physics: “Physical Frontiers in Biology: A Resource for Students and Faculty” (Volume 74, Pages 375–381). Russ and I mentioned this publication in our 2009 “Resource Letter on Medical Physics,” where we wrote that Mielczarek’s letter “begins with a fascinating three-page essay on the role of physics in biology.” This week I discovered that the published black-and-white pictures in that 3-page essay are available in color at Mielczarek’s website. Mielczarek is an editor of the 1993 book Biological Physics, a collection of landmark biological physics papers. One of her research interests is the role of iron in biological systems, and in 2000 she coauthored the book Iron, Nature’s Universal Element: Why People Need Iron and Animals Make Magnets, which I just put onto my summer reading list. We cite this “very readable” book in Section 8.8.3 of Intermediate Physics for Medicine and Biology, but it must have been one of those things that Russ added to the 4th edition because I haven’t read it yet. We also cite Mielczarek’s American Journal of Physics paper “Experimental and Theoretical Models of Nonlinear Behavior" in Chapter 10 of our book.

For more information about the physics of therapeutic touch, see the article “Emerita Professor Makes a Case Against Distance Healing” in the Mason Gazette, and the press release “Think Tank Objects to Taxpayer Funding for Therapeutic Touch, other Alternative Medicine Therapies” from the Center of Inquiry.

Let us hope that hope that Bob Park and Eugenie Mielczarek continue to debunk the techniques of “alternative medicine” when they violate the laws of physics.

Friday, April 16, 2010

PHY 530, Bioelectric Phenomena

This week I finished up my PHY 530 class (Bioelectric Phenomena), which I discussed once before in this blog. Rather than adopting a textbook, I based this graduate class on a collection of scientific papers. Below I list the three dozen papers we studied. It should not be regarded as a “greatest hits” list. Some are Nobel Prize winning papers, but oftentimes I selected a lesser-known article that happened to cover a specific topic I wanted to teach. Many are cited in the 4th edition of Intermediate Physics for Medicine and Biology (indicated by a *). Students were assigned the 16 papers marked in bold: they had to take a quiz on each of these before we discussed them in class, and the exams often contained questions drawn directly from these papers. The other 20 articles are supplementary: consider them recommended reading, rather than required.

I had two goals in the class: to teach the basic elements of bioelectricity, and to lead a workshop on how to write a scientific paper. The students were given two projects (one was to simulate a squid nerve axon using the Hodgkin-Huxley model, and the other was to determine a dipole source from simulated EEG data) and had to write up their results in a brief (4 page maximum) paper having the classic structure: Abstract, Introduction, Methods, Results, Discussion, References. We read essays related to writing scientific papers, such as "What's Wrong With These Equations?" and "Writing Physics," both by N. David Mermin, and learned to use the Science Citation Index. I am pleased with how the class went, and I hope the students were too.
1. A. L. Hodgkin and A. F. Huxley (1939) “Action Potentials Recorded from Inside a Nerve Fiber,” Nature, Volume 144, Pages 710–711. *

2. A. L. Hodgkin and B. Katz (1949) The Effect of Sodium Ions on the Electrical Activity of the Giant Axon of the Squid,” Journal of Physiology, Volume 108, Pages 37–77.

3. A. L. Hodgkin and A. F. Huxley (1952) A Quantitative Description of Membrane Current and its Application to Conduction and Excitation in Nerve, Journal of Physiology, Volume 117, Pages 500544. *

4. D. A. Doyle, J. M. Cabral, R. A. Pfuetzner, A. Kuo, J. M. Gulbis, S. L. Cohen, B. T. Chait, and R. MacKinnon (1998) The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity, Science, Volume 280, Pages 6977. *

5. O. P. Hamill, A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth (1981) Improved Patch-Clamp Techniques for High-Resolution Current Recording From Cells and Cell-Free Membrane Patches, Pflugers Archive, Volume 391, Pages 85100. *

6. A. L. Hodgkin and W. A. H. Rushton (1946) The Electrical Constants of a Crustacean Nerve Fibre, Proceedings of the Royal Society of London, B, Volume 133, Pages 444479. *

7. W. A. H. Rushton (1951) “A Theory of the Effects of Fibre Size in Medullated Nerve,” Journal of Physiology, Volume 115, Pages 101–122. *

8. R. FitzHugh (1961) “Impulses and Physiological States in Theoretical Models of Nerve Membrane,” Biophysical Journal, Volume 1, Pages 445–466.

9. W. Rall (1962) “Theory of Physiological Properties of Dendrites,” Annals of the New York Academy of Sciences, Volume 96, Pages 1071–1092.

10. F. Rattay (1989) Analysis of Models for Extracellular Fiber Stimulation, IEEE Transactions on Biomedical Engineering, Volume 36, Pages 676682.

11. A. T. Barker, R. Jalimous, and I. L. Freeston (1985) Non-Invasive Magnetic Stimulation of Human Motor Cortex,” Lancet, Volume 8437, Pages 11061107. *

12. M. Hallett and L. G. Cohen (1989) “Magnetism: A New Method for Stimulation of Nerve and Brain,” Journal of the American Medical Association, Volume 262, Pages 538–541. *

13. B. J. Roth, L. G. Cohen and M. Hallett (1991) “The Electric Field Induced During Magnetic Stimulation,” Electroencephalography and Clinical Neurophysiology, Supplement 43, Pages 268–278.

14. R. Plonsey (1974) The Active Fiber in a Volume Conductor,” IEEE Transactions on Biomedical Engineering, Volume 21, Pages 371381.

15. B. J. Roth, D. Ko, I. R. von Albertini-Carletti, D. Scaffidi and S. Sato (1997) Dipole Localization in Patients with Epilepsy Using the Realistically Shaped Head Model, Electroencephalography and Clinical Neurophysiology, Volume 102, Pages 159166.

16. M. Schneider (1974) “Effect of Inhomogeneities on Surface Signals Coming From a Cerebral Current-Dipole Source,” IEEE Transactions on Biomedical Engineering, Volume 21, Pages 52–54.

17. B. J. Roth and J. P. Wikswo (1985) The Magnetic Field of a Single Axon: A Comparison of Theory and Experiment,” Biophysical Journal, Volume 48, Pages 93109. *

18. M. Hamalainen, R. Hari, R. J. Ilmoniemi, J. Knuutila, and O. V. Lounasmaa (1993) “Magnetoencephalography: Theory, Instrumentation, and Application to Noninvasive Studies of the Working Human Brain,” Reviews of Modern Physics, Volume 65, Pages 413–497. *

19. T.-K. Truong and A. W. Song (2006) Finding Neuroelectric Activity Under Magnetic-Field Oscillations (NAMO) with Magnetic Resonance Imaging In Vivo,” Proceedings of the National Academy of Sciences, Volume 103, Pages 1259812601.

20. B. J. Roth and P. J. Basser (2009) “Mechanical Model of Neural Tissue Displacement During Lorentz Effect Imaging,” Magnetic Resonance in Medicine, Volume 61, Pages 59–64.

21. A. T. Winfree (1987) When Time Breaks Down. Princeton Univ Press, Princeton, NJ, Pages 106–107. *

22. B. J. Roth (2002) “Virtual Electrodes Made Simple: A Cellular Excitable Medium Modified for Strong Electrical Stimuli,” The Online Journal of Cardiology, http://sprojects.mmi.mcgill.ca/heart/pages/rot/rothom.html

23. D. W. Frazier, P. D. Wolf, J. M. Wharton, A. S. L. Tang, W. M. Smith and R. E. Ideker (1989) Stimulus-Induced Critical Point: Mechanism for Electrical Initiation of Reentry in Normal Canine Myocardium,” Journal of Clinical Investigation, Volume 83, Pages 10391052.

24. N. Shibata, P.-S. Chen, E. G. Dixon, P. D. Wolf, N. D. Danieley, W. M. Smith, and R. E. Ideker (1988) “Influence of Shock Strength and Timing on Induction of Ventricular Arrhythmias in Dogs,” American Journal of Physiology, Volume 255, Pages H891–H901.

25. J. N. Weiss, A. Garfinkel, H. S. Karagueuzian, Z. Qu and P.-S. Chen (1999) Chaos and the Transition to Ventricular Fibrillation: A New Approach to Antiarrhythmic Drug Evaluation,” Circulation, Volume 99, Pages 28192826.

26. A. Garfinkel, Y.-H. Kim, O. Voroshilovsky, Z. Qu, J. R. Kil, M.-H. Lee, H. S. Karagueuzian, J. N. Weiss, and P.-S. Chen (2000) “Preventing Ventricular Fibrillation by Flattening Cardiac Restitution,” Proceedings of the National Academy of Sciences, Volume 97, Pages 6061–6066. *

27. N. G. Sepulveda, B. J. Roth and J. P. Wikswo, Jr. (1989) Current Injection into a Two-Dimensional Anisotropic Bidomain,” Biophysical Journal, Volume 55, Pages 987999. *

28. B. J. Roth (1992) “How the Anisotropy of the Intracellular and Extracellular Conductivities Influences Stimulation of Cardiac Muscle,” Journal of Mathematical Biology, Volume 30, Pages 633–646. *

29. Efimov I. R., Y. Cheng, D. R. Van Wagoner, T. Mazgalev, and P. J. Tchou (1998) Virtual Electrode-Induced Phase Singularity: A Basic Mechanism of Defibrillation Failure,” Circulation Research, Volume 82, Pages 918925.

30. Efimov, I. R., Y. N. Cheng, M. Biermann, D. R. Van Wagoner, T. N. Mazgalev, and P. J. Tchou (1997) “Transmembrane Voltage Changes Produced by Real and Virtual Electrodes During Monophasic Defibrillation Shock Delivered by an Implantable Electrode,” Journal of Cardiovascular Electrophysiology, Volume 8, Pages 1031–1045.

31. Roth, B. J. (1995) “A Mathematical Model of Make and Break Electrical Stimulation of Cardiac Tissue Using a Unipolar Anode or Cathode,” IEEE Transactions on Biomedical Engineering, Volume 42, Pages 1174–1184.

32. Cheng, Y., V. Nikolski, and I. R. Efimov (2000) “Reversal of Repolarization Gradient Does Not Reverse the Chirality of the Shock-Induced Reentry in the Rabbit Heart,” Journal of Cardiovascular Electrophysiology, Volume 11, Pages 998–1007.

33. Trayanova, N. A., B. J. Roth, and L. J. Malden (1993) The Response of a Spherical Heart to a Uniform Electric Field: A Bidomain Analysis of Cardiac Stimulation,” IEEE Transactions on Biomedical Engineering, Volume 40, Pages 899908.

34. Nielsen, P. M. F., I. J. Le Grice, B. H. Smaill, and P. J. Hunter (1991) “Mathematical Model of Geometry and Fibrous Structure of the Heart,” American Journal of Physiology, Volume 260, Pages H1365–H1378.

35. Krassowska, W., T. C. Pilkington, and R. E. Ideker (1987) “The Closed Form Solution to the Periodic Core-Conductor Model Using Asymptotic Analysis,” IEEE Transactions on Biomedical Engineering, Volume 34, Pages 519–531.

36. Rodriquez, B., J. C. Eason, and N. Trayanova (2006) “Differences Between Left and Right Ventricular Anatomy Determine the Types of Reentrant Circuits Induced by an External Electric Shock: A Rabbit Heart Simulation Study,” Progress in Biophysics and Molecular Biology, Volume 90, Pages 399–413.