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that were presumably primitively present the associated thermal energy (equal to the identity, leading to a view of evolution in in the Xenoturbella lineage but have since product kT, where k is Boltzmann’s constant been lost. This means that Xenoturbella is and T is the temperature in kelvin) is too secondarily simplified rather than pristine small to allow relative particle motion, as it and primitive, and may not be as reliable does in ordinary liquids. So dynamic collec- however, not least by work on enteropneusts tions of grains require a continuous external source of energy to prevent them from get- complexity of gene expression5. Xenoturbella As we reflect on Xenoturbella’s newly ting stuck in a particular configuration.
exalted state as a deuterostome, it is worth ancestry, if not the ancestry of both deutero- recalling similar examples. Aristotle classed energy is typically injected through a surface stomes and protostomes. Classifying it as a (a stirring rod, shear zone or vibrating wall, flatworm, therefore, might not have been so amphioxus, when first described, was named for example),steep gradients of kinetic energy far from the truth, as that is what the earliest Limax lanceolatus — a kind of slug. So there are invariably present in the system, caused is no shame in having once been classed as a by the decrease in relative particle motion further from the energy source and by the leagues3 have placed Xenoturbella closer to spatial anisotropies arising from the direc- the ambulacraria than to the root of deutero- Henry Gee is a senior editor at Nature. tional nature of the forcing. These complica- stomes in general raises further problems, 1. Norén, M. & Jondelius, U. Nature 390, 31–32 (1997).
for it means that it cannot represent a truly 2. Israelsson, O. Nature 390, 32 (1997).
liquids can be described by the traditional primitive state. Ambulacraria and chordates 3. Bourlat, S. J., Nielsen, C., Lockyer, A. E., Littlewood, D. T. J. & Telford, M. J. Nature 424, 925–928 (2003).
share anatomical features, such as a body 4. Shu, D.-G. et al. Nature 414, 419–424 (2001).
statistical mechanics5,7,8. And they are the cavity and structures called pharyngeal slits, 5. Lowe, C. J. et al. Cell 113, 853–865 (2003).
major reasons why granular materialsremain one of the least well understoodclasses of matter.
Granular materials
plications associated with the lack of energyconservation in granular media, D’Anna et Shaken sand — a granular fluid?
al.6 have attacked the problem directly by studying the response of vertically vibratedglass beads (physicists’ equivalent of sand), The connection between random grain motion and viscosity in shaken using a beefed-up version of the aforemen- sand — a strongly non-equilibrium system — has been probed. Curiously, tioned pendulum (pictured on the cover of the link is similar to that found in an ordinary liquid in thermal equilibrium.
this issue). Their bead-filled container is driven with band-filtered white noise at a pills, breakfast cereal and, not least of all, relatively high frequency, which ensures that sand — are usually defined to be discrete no single characteristic frequency dominates oscillations of a rigid pendulumimmersed in an ordinary liquid, the the forcing, that the natural frequency of the temperature and viscosity of the liquid can through energy-dissipating contact forces oscillator is far below the driving frequency, be determined1. This is due, in part, to a relation from equilibrium statistical mech- stretched to include wetted grains and pendulum probe is operated in two modes: anics known as the fluctuation–dissipation powders for which attractive surface forces free and forced. In the free mode, a constant theorem2, which, in a precursor to its mod- are also important).Many industrial practices ern form, was devised by Einstein3 to explain require the efficient handling and mixing of jostles it about in irregular excursions about the diffusive Brownian motion of small par- granular materials: food and agricultural its equilibrium position. Analysis of this ticles suspended in liquids4. Driven granular processing, sorting and assembly of parts, Brownian-like motion gives the ‘noise power materials, such as shaken sand, are systems spectral density’ in terms of the driving far from equilibrium — they have strong frequency. In the forced mode, a sinusoidal spatial and temporal variations in quantities torque is applied to the oscillator, and such as density and local particle velocity, and would consequently not be expected to ials behave unusually because they combine obey the fluctuation–dissipation theorem.
properties of both liquids and solids7,8.
behaviour of granular materials seems, at least superficially, liquid-like5. One might waves or ripples when shaken10 or blown11, described by the theory developed for equi- librium fluids — one of the two parameters a rigid pendulum would reveal a similar can attest who has walked on wet sand and used in the fit to theory being the friction fluctuation–dissipation relation in driven observed a dry halo around their foot).
coefficient, which is proportional to the granular materials, despite their dissipative shaken beads’ viscosity. Furthermore, the nature. On page 909 of this issue6, D’Anna lar materials arise because, unlike an ordi- bead viscosity is found to decrease nearly nary fluid, the kinetic energy associated with find, surprisingly, that the answer seems to the relative motion of macroscopic particles be yes. In particular, their experiments show (called ‘granular temperature’ by physicists) decrease in viscosity with increasing temper- that the free and forced motions of the probe is not constant. Instead, it is continually and ature — nearly a factor of three for water are related by a fluctuation–dissipation-like irrevocably transferred by collisions to inter- relation, and that an effective viscosity and nal (thermal or non-kinetic) degrees of free- dom. Although individual grains possess a leagues’ finding6 concerning the so-called Granular materials — such as peas, coal, fluctuation–dissipation ratio, which is NATURE | VOL 424 | 21 AUGUST 2003 | www.nature.com/nature 2003 Nature Publishing Group
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derived from the complex susceptibility and liquids. Some puzzles remain. Why does the the two drugs most commonly used to treat effective temperature vary by approximately a malaria4. Hope for the containment of the relates collective response to individual factor of 10 for differently shaped probes? disease now rests largely on a remarkable set grain motion.This ratio turns out to be nearly What influence does the probe have on the of artemisinin drugs developed by Chinese scientists in the 1970s and early 1980s, which enables D’Anna et al. to define an effective dissipation ratio an increasing function of temperature for the grains. For a classical frequency (albeit slowly)? The answers them- The parasites are small ‘protozoan’ cells liquid, this ratio is equal to kT and is strictly selves may be mundane,but they might lead to (the most prevalent species infecting humans independent of frequency. Using the average deeper insights into the properties of granular are Plasmodium falciparum and P. vivax), value of the ratio as their measure of thermal materials and other related non-equilibrium energy, the authors show that the tempera- subjects such as traffic flow, flocking, evolving mosquito bite. They first invade the liver and ture increases as the square of the driving- replicate there for two weeks, before begin- force amplitude — a result that would be Paul Umbanhowar is in the Department of Physics ning a cycle of red-blood-cell invasion, then naively expected if the bead velocities were and Astronomy, Northwestern University, growth, replication and red-cell destruction linearly related to the container velocity, which in turn increases in direct proportion artemisinin drugs are known to act specifi- to the drive amplitude. These findings are intriguing, and they support results from 1. Uhlenbeck, G. E. & Goudsmit, S. Phys. Rev. 34, 145–151 (1929).
Artemisinin contains a structural feature other analyses of model systems that have 2. Reichl, L. E. A Modern Course in Statistical Physics 545–560 called a peroxide bridge (Fig. 1), and this is indicated that the fluctuation–dissipation believed to be the key to the drug’s mode 3. Einstein, A. Ann. Physik 17, 549–560 (1905).
theorem, or a slightly modified version of it, 4. Brown, R. Phil. Mag. 4, 161–173 (1828).
of action. Ferrous iron (Fe2+) catalyses the applies to granular materials13–15. There are 5. Jaeger, H. M., Nagel, S. R. & Behringer, R. P. Rev. Mod. Phys. 68,
also signs that the temperatures obtained reactive free radicals5. The theory has been 6. D’Anna, G., Mayor, P., Barrat, A., Loreto, V. & Nori, F. Nature through application of the fluctuation– that these artemisinin-derived free radicals 424, 909–912 (2003).
dissipation theorem13 are compatible with 7. Kadanoff, L. P. Rev. Mod. Phys. 71, 435–444 (1999).
chemically modify and inhibit a variety of 8. de Gennes, P. G. Rev. Mod. Phys. 71, S374–S382 (1999).
parasite molecules, resulting in parasite of statistical mechanics that is applicable to 9. Makse, H. A., Havlin, S., King, P. R. & Stanley, H. E. Nature 386,
granular systems and possibly to other non- 10. Melo, F., Umbanhowar, P. B. & Swinney, H. L. Phys. Rev. Lett. 75,
haem — an essential component of haemo- 11. Bagnold, R. A. The Physics of Blown Sand and Desert Dunes globin — and it has long been suspected that
granular ensembles with strong dissipation 12. Reynolds, O. Phil. Mag. 20, 469 (1885).
have a definable viscosity and approximately 13. Makse, H. A. & Kurchan, J. Nature 415, 614–617 (2002).
artemisinins inside the parasite. In support obey the fluctuation–dissipation theorem are 14. Aumaitre, S., Fauve, S., McNamara, S. & Poggi, P. Eur. Phys. J. B of this, Fe2+-haem activates artemisinins in exciting, but they do not yet definitively 19, 449–460 (2001).
the test tube and haem–artemisinin com- 15. Colizza, V., Barrat, A. & Loreto, V. Phys. Rev. E 65, 050301(R) (2002).
answer the question of how deep the similarities plexes can be formed. This theory appealed 16. Edwards, S. F. in Granular Matter: An Interdisciplinary Approach (ed. Mehta, A.) 121–140 (Springer, New York, 1994).
to malariologists because it seemed toexplain the specificity of the drug within thecontext of a unique aspect of parasite metab- olism. During its growth and replicationinside the red blood cell, the parasite ingestsand degrades up to 80% of host-cell haemo- To kill a parasite
vacuole. This releases Fe2+-haem, which isoxidized to Fe3+-haematin and then aggre- Artemisinins have been used since ancient times to treat malaria. A gates within the food vacuole into an ordered new theory could explain how this age-old medicine is able to cause theory developed that the specific antimalar-ial effect of artemisinin was due to its entry five living in sub-Saharan Africa, but the into the parasite food vacuole and its inter-disease also afflicts Southeast Asia, South action with Fe2+-haem. Here, it would set off The Chinese herb qinghao (Artemisia annua) has long been used to treatmalaria — Taoist manuscripts dating a ‘cluster bomb’ of free radicals, inhibiting back to the third century describe the use of situation has worsened over recent years as several key parasite components and even- qinghao extracts to treat malaria-related fevers1. Over the past two decades, deriva- This theory has been challenged7,however, tives of the herb’s active ingredient,artemisinin, have made an increasing contribution to malaria treatment. But the derivatives kill the parasite has remained obscure. Writing on page 957 of this issue, Krishna and colleagues2 propose a radical new theory to explain the molecular basis ofthe antimalarial activity of artemisinin.
Malaria remains a scourge of the develop- ing world, killing over a million people each Figure 1 Structure of artemisinin. The molecule contains a peroxide bridge (red), which becomes
year and infecting around 500 million3. Most cleaved when artemisinin interacts with ferrous iron (Fe2+Ꮞ. Cleavage creates ‘C4’ and ‘seco-C4’ free
of the victims are children under the age of radicals, each capable of chemically modifying biological molecules.
NATURE | VOL 424 | 21 AUGUST 2003 | www.nature.com/nature 2003 Nature Publishing Group

Source: http://dml.riken.go.jp/pub/nori/pdf/Nature_424_886.pdf