Friday, January 31, 2014

The Feynman Lectures on Physics: New Millennium Edition

Several years ago in this blog, I discussed The Feynman Lectures on Physics. Russ Hobbie and I cite the Feynman Lectures in Chapter 11 of the 4th Edition of Intermediate Physics for Medicine and Biology. Recently, a new millennium edition of the Feynman Lectures has been produced and it is fully online: If you are reading this blog, you can read the Feynman Lectures, free and open to all. The preface to the millennium edition states
“Nearly fifty years have passed since Richard Feynman taught the introductory physics course at Caltech that gave rise to these three volumes, The Feynman Lectures on Physics. In those fifty years our understanding of the physical world has changed greatly, but The Feynman Lectures on Physics has endured. Feynman's lectures are as powerful today as when first published, thanks to Feynman's unique physics insights and pedagogy. They have been studied worldwide by novices and mature physicists alike; they have been translated into at least a dozen languages with more than 1.5 millions copies printed in the English language alone. Perhaps no other set of physics books has had such wide impact, for so long.
This New Millennium Edition ushers in a new era for The Feynman Lectures on Physics (FLP): the twenty-first century era of electronic publishing. FLP has been converted to eFLP, with the text and equations expressed in the LaTeX electronic typesetting language, and all figures redone using modern drawing software.
The consequences for the print version of this edition are not startling; it looks almost the same as the original red books that physics students have known and loved for decades. The main differences are an expanded and improved index, the correction of 885 errata found by readers over the five years since the first printing of the previous edition, and the ease of correcting errata that future readers may find. To this I shall return below.
The eBook Version of this edition, and the Enhanced Electronic Version are electronic innovations. By contrast with most eBook versions of 20th century technical books, whose equations, figures and sometimes even text become pixellated when one tries to enlarge them, the LaTeX manuscript of the New Millennium Edition makes it possible to create eBooks of the highest quality, in which all features on the page (except photographs) can be enlarged without bound and retain their precise shapes and sharpness. And the Enhanced Electronic Version, with its audio and blackboard photos from Feynman's original lectures, and its links to other resources, is an innovation that would have given Feynman great pleasure.”
All three volumes of this classic text are online. There is a lot of extra stuff too, like an errata for each edition, exercises with solutions, stories from many physicists about how the Feynman Lectures influenced their careers, original course handouts, and related links. And did I mention it is available free and open to all?


Friday, January 24, 2014

Drosophila melanogaster

In Chapter 9 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss how the patch clamp technique combined with genetics methods can be used to answer scientific questions. One example we consider is the potassium channel in the fruit fly.
“Gene splicing combined with patch-clamp recording provided a wealth of information. Regions of the DNA responsible for synthesizing the membrane channel have been identified. One example that has been extensively studied is a potassium channel from the fruit fly, Drosophila melanogaster. The Shaker fruit fly mutant shakes its legs under anesthesia. It was possible to identify exactly the portion of the fly’s DNA responsible for the mutation. When Shaker DNA was placed in other cells that do not normally have potassium channels, they immediately made functioning channels.”
So what is Drosophila melanogaster, and why is it significant? Horace Freeland Judson describes this famous model system in his masterpiece The Eighth Day of Creation: The Makers of the Revolution in Biology. In his Chapter 4, On T. H. Morgan’s Deviation and the Secret of Life, Judson writes
“Thinking of T. H. Morgan, one thinks first, or should, of the common vinegar fly, Drosophila, whose mutants and hybrids and their multitudinous descendants he examined for red eyes and eosin eyes and white eyes, vestigial wings or wild-type, and so on, and which he kept as best he could in hundreds of milk bottles stoppered with cotton wool. With Drosophila, Morgan discovered, for example, the mechanism by which sex is determined, at the instant of the egg’s fertilization, by the pairing of the sex chromosomes, either XX or XY, and the consequent phenomenon of sex-linked inheritance that explains, as we all also know, the appearance of disorders like hemophilia among the male descendants of Queen Victoria. And when Morgan and a student of his, Alfred Henry Sturtevant, perceived that the statistical evidence for linkage of many genes on one chromosome could be extended to map their relative distance one from another along that chromosome, then the hereditary material became palpably a string of beads, a line of points, each controlling a character of the organism.”
In The Wellsprings of Life, Isaac Asimov describes the same experiments.
“What was needed [to understand genetics] was a simpler type of organism [compared to humans]; one that was small and with few needs, so that it might easily be kept in quantity; one that bred frequently and copiously; and one that had cells with but a few chromosomes. An organism which met all these needs ideally was first used in 1906 by the American zoologist Thomas Hunt Morgan. This was the common fruit fly, of which the scientific name is the much more formidable Drosophila melanogaster (‘the black-bellied moisture-lover’). These are tiny things, only about one twenty-fifth of an inch long, and can be kept in bottles with virtually no trouble. They can breed every two weeks, laying numerous eggs each time. Their cells have only eight chromosomes apiece (with four in the gametes).

More genetic experiments have been conducted with Drosophila in the past half-century [Asimov was writing in 1960] than with any other organism, and Morgan received the Nobel prize in medicine and physiology in 1933 for the work he did with the little insect. Enough work was done with other organisms, from germs to mammals, to show that the results obtained from Drosophila studies are quite general, applying to all species.”
If you want to learn more about Drosophila, I suggest the article Drosophila melanogaster: a fly through its history and current use by Stephenson and Metcalfe (Journal of the Royal College of Physicians of Edinburgh, Volume 43, Pages 70-75, 2013). For those who prefer video, here is a great introduction to Drosophila from the Journal of Visualized Experiments, JoVE. Finally, for our 5-year-old readers (or the young at heart), you can purchase a Drosophila melanogaster plush toy here for just ten dollars.

Friday, January 17, 2014

George Ralph Mines

In Chapter 10 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the contribution of George Ralph Mines to cardiac electrophysiology.
“The propagation of an action potential is one example of the propagation of a wave in excitable media. We saw in Chap. 7 that waves of depolarization sweep through cardiac tissue. The circulation of a wave of contraction in a ring of cardiac tissue was demonstrated by Mines in 1914. It was first thought that such a wave had to circulate around an anatomic obstacle, but it is now recognized that no obstacle is needed.”
This year marks the 100th anniversary of Mines’ landmark work. Regis DeSilva, in an article titled George Ralph Mines, Ventricular Fibrillation and the Discovery of the Vulnerable Period (Journal of the American College of Cardiology, Volume 29, Pages 1397-1402, 1997) describes Mines’ work in more detail.
“George Ralph Mines … made two major contributions to electrophysiology. His scientific legacy includes elucidating the theoretical basis for the occurrence of reentrant arrhythmias and the discovery of the vulnerable period of the ventricle.” 
First, DeSilva discusses Mines’ analysis of reentry in cardiac tissue.
“Mines applied his concept of reentry to myocardial tissue and suggested that closed circuits may also exist within heart muscle. Under normal conditions, these circuits are uniformly excited, and an excitatory wave dies out. He suggested that the twin conditions of unidirectional block and slow conduction may occur in abnormal myocardial tissue. Thus, tissue in a reentrant circuit may allow a circulating wavefront to be sustained by virtue of conductive tissue being always available for excitation. In this paper, he also published a now classic figure by illustrating the concept of circus movement in such small myocardial circuits, and this diagram is still used unchanged today in teaching this mechanism to students of electrocardiography (14)”
Reference 14 (Mines GR, On Dynamic Equilibrium in the Heart, Journal of Physiology, Volume 46, Pages 349-383, 1913) is not cited in IPMB.

DeSilva then addresses Mines identification of a “vulnerable period” in the heart.
“Mines’ second major contribution was also his most important discovery. It was published … in 1914, entitled 'On Circulating Excitations in Heart Muscles and Their Possible Relation to Tachycardia and Fibrillation'  [Transactions of the Royal Society of Canada, Volume 8, Pages 43-52, 1914] (15).…[Before 1914] the most common method of inducing fibrillation was by the application of repeated electrical shocks to the heart through an induction coil. Mines’ innovation in studying the onset of fibrillation was to modify the method by applying single shocks to the rabbit heart, and by timing them precisely at various periods during the cardiac cycle.… Stimuli were delivered by single taps of a Morse key, and the moment of application of the stimulus was signaled by the use of a sparking coil connected to an insulated pointer that produced dots on the kymographic trace. Correlation of the position of the dots on the mechanical trace with the electrocardiogram provided an indication of its timing in electrical diastole…. By so doing, ‘it was found in a number of experiments that a single tap of the Morse key if properly timed [his italics] would start fibrillation which would persist for a time. . . . The point of interest is that the stimulus employed would never cause fibrillation unless it was set in at a certain critical instant’ (15)…. The importance of this work lies in the fact that Mines identified for the first time a narrow zone fixed within electrical diastole during which the heart was extremely vulnerable to fibrillation. An external stimulus, or a stimulus generated from within the heart, if properly timed to fall within this zone, could trigger a fatal arrhythmia and cause death. This observation has spurred three generations of scientists to study the factors which cause death by disruption of what Mines called 'the dynamic equilibrium of the heart' (14).”
Clearly Mines made landmark contributions to our understanding of the heart. But perhaps the most intriguing aspect of Mines’ life was the unusual circumstances of his untimely death. DeSilva writes
“On the evening of Saturday November 7, 1914, the night janitor entered Mines’ laboratory and found him lying unconscious with equipment attached, apparently for the recording of respiration (25). He was taken immediately to the Royal Victoria Hospital where he regained consciousness only briefly. Shortly before midnight, he developed seizures and died without regaining consciousness. A complete autopsy was performed, including examination of all the abdominal and thoracic viscera and the brain, but no final diagnosis was rendered (26). The presumption was that death resulted from self-experimentation.”
Here is how Art Winfree describes the same event, in his Scientific American article Sudden Cardiac Death: A Problem in Topology:
“Mines had been trying to determine whether relatively small, brief electrical stimuli can cause fibrillation. For this work he had constructed a device to deliver electrical impulses to the heart with a magnitude and timing that could be precisely controlled. The device had been employed in preliminary work with animals. When Mines decided it was time to begin work with human beings, he chose the most readily available experimental subject: himself. At about six o’clock that evening a janitor, thinking it was unusually quiet in the laboratory, entered the room. Mines was lying under the laboratory bench surrounded by twisted electrical equipment. A broken mechanism was attached to his chest over the heart and a piece of apparatus nearby was still recording the faltering heartbeat. He died without recovering consciousness.”
Winfree notes in the 2nd edition of his book The Geometry of Biological Time that there is still some controversy about if Mines' death was truly from self experimentation. The circumstances of his death are certainly suggestive of this, even if we lack definitive proof.

I can't help but notice the similarities between George Ralph Mines and Henry Moseley. Both were Englishmen whose last name started with "M". Both were born at about the same time (Mines in 1886, Moseley in 1887). Both made fundamental contributions to science at an early age (Mines to cardiac electrophysiology, and Moseley to our understanding of the atomic number and the periodic table). Both are probably underappreciated in the history of science, and neither won the Nobel Prize. And both died before reaching the age of 30 (Mines in 1914, Moseley in 1915). Mines died in the mysterious accident in his lab described above, and Moseley died in the Battle of Gallipoli during World War I. And, of course, both are mentioned in the 4th edition of Intermediate Physics for Medicine and Biology.

Friday, January 10, 2014

Happy Birthday, Earl Bakken!

Today, Earl Bakken turns 90 years old. Bakken is the founder of the medical device company Medtronic, and he played a key role in the development of the artificial pacemaker. I had the good fortune to meet Bakken in 2009 at a reception in the Bakken Museum as part of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society held in Minneapolis.

Kirk Jeffrey’s book Machines in our Hearts tells the story of how Bakken, at the request of the renowned heart surgeon C. Walton Lillehei, developed the first battery powered pacemaker.
“Bakken first thought of an ‘automobile battery with an inverter to convert the six volts to 115 volts to run the AC pacemaker on its wheeled stand. That, however, seemed like an awfully inefficient say to do the job, since we needed only a 10-volt direct-current pulse to stimulate the heart.’ Powering the stimulator from a car battery would have eliminated the need for electrical cords and plugs, but would not have done away with the wheeled cart. Bakken then realized that he could simply build a stimulator that used transistors and small batteries. ‘It was kind of an interesting point in history,’ he recalled—‘a joining of several technologies.’ In constructing the external pulse generator, Bakken borrowed a circuit design for a metronome that he had noticed a few months earlier in an electronics magazine for hobbyists. It included two transistors. Invented a decade earlier, the transistor was just beginning to spread into general use in the mid-1950s. Hardly anyone had explored its applications in medical devices. Bakken used a nine-volt battery, housed the assemblage in an aluminum circuit box, and provided an on-off switch and control knobs for stimulus rate and amplitude.

At the electronics repair shop that he had founded with his brother-in-law in 1949, Bakken had customized many instruments for researchers at the University of Minnesota Medical School and the nearby campus of the College of Agriculture. Investigators often ‘wanted special attachments or special amplifiers’ added to some of the standard recording and measuring equipment. ‘So we began to manufacture special components to go with the recording equipment. And that led us into just doing specials of many kinds…We developed….animal respirators, semen impedance meters for the farm campus, just a whole spectrum of devices.’ Usually the business would sell a few of these items. When Bakken delivered the battery-powered external pulse generator to Walt Lillehei in January 1958, it seemed to the inventor another special order, nothing more. The pulse generator was hardly an aesthetic triumph, but it was small enough to hold in the hand and severed all connection between the patient’s heart and the hospital power system. Bakken’s business had no animal-testing facility, so he assumed that the surgeons would test the device by pacing laboratory dogs. They did ‘a few dogs,’ then Lillehei put the pacemaker into clinical use. When Bakken next visited the university, he was surprised to find that his crude prototype was managing the heartbeat of a child recovering from open-heart surgery.”
Russ Hobbie and I discuss the artificial pacemaker in Chapter 7 of the 4th edition of Intermediate Physics for Medicine and Biology
“Cardiac pacemakers are a useful treatment for certain heart diseases [Jeffrey (2001), Moses et al. (2000); Barold (1985)]. The most frequent are an abnormally slow pulse rate (bradycardia) associated with symptoms such as dizziness, fainting (syncope), or heart failure. These may arise from a problem with the SA node (sick sinus syndrome) or with the conduction system (heart block). One of the first uses of pacemakers was to treat complete or “third degree” heart block. The SA node and the atria fire at a normal rate but the wave front cannot pass into the conduction system. The AV node or some other part of the conduction system then begins firing and driving the ventricles at its own, pathologically slower rate. Such behavior is evident in the ECG in Fig. 7.30, in which the timing of the QRS complex from the ventricles is unrelated to the P wave from the atria. A pacemaker stimulating the ventricles can be used to restore a normal ventricular rate.”
You can learn more about Bakken’s contributions to the development of the pacemaker here or on video here. Visit his website here or read his autobiography. He now lives in Hawaii, where local magazines have reported about him here and here. Those wanting to join the celebration can attend Earl Bakken’s birthday bash at the Bakken Museum, or celebrate at the North Hawaii Community Hospital.

Happy birthday, Earl Bakken!

Friday, January 3, 2014

Integrals of Sines and Cosines

Last week in this blog, I discussed the Fourier series. This week, I want to highlight some remarkable mathematical formulas that make the Fourier series work: integrals of sines and cosines. The products of sine and cosines obey these relationships:
where n and m are integers. In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I dedicate Appendix E to studying these integrals. They allow some very complicated expressions involving infinite sums to reduce to elegantly simple equations for the Fourier coefficients. Whenever I am teaching Fourier Series, I go through the derivation up to the point where these integrals are needed, and then say “and now the magic happens!”

The collection of sines and cosines (sinmx, cosnx) are an example of an orthogonal set of functions. How do you prove orthogonality? One can derive it using the trigonometric product-to-sum formulas.
I prefer to show that these integrals are zero for some special cases, and then generalize. Russ and I do just that in Figure E2. When we plot (a) sinx sin2x and (b) sinx cosx over the range 0 to 2π, it becomes clear that these integrals are zero. We write “each integrand has equal positive and negative contributions to the total integral,” which is obvious by merely inspecting Fig. E2. Is this a special case? No. To see a few more examples, I suggest plotting the following functions between 0 and 2π:
In each case, you will see the positive and negative regions cancel pairwise. It really is amazing. But don’t take my word for it, as you’ll miss out on all the fun. Try it.

Nearly as amazing is what happens when you analyze the case for m = n by integrating cosnx cosnx = cos2nx or sinnx sinnx=sin2nx. Now the integrand is a square, so it always must be positive. These integrals do not vanish (although the “mixed” integral cosnx sinnx does go to zero). How do I remember the value of this integral? Just recall that the average value of either cos2nx or sin2nx is ½. As long as you integrate over an integral number of periods, the result is just π.

When examining non-periodic functions, one integrates over all x, rather than from merely zero to 2π. In this case, Russ and I show in Sec. 11.10 that you get delta function relationships such as
I won’t ask you to plot the integrand over x, because since x goes from negative infinity to infinity it might take you a long time.

The integrals of products of sines and cosines is one example of how Russ and I use appendicies to examine important mathematical results that might distract the reader from the main topic (in this case, Fourier series and its application to imaging), but are nevertheless important.