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ScienceWeek
ScienceWeek - May 31, 2002 Vol. 6 Number 22
An Online Research Digest Published Weekly Since 1997
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Scientifically speaking, a butterfly is at least as mysterious
as a superstring. When something ceases to be mysterious, it
ceases to be of absorbing concern to scientists. Almost all the
things scientists think and dream about are mysterious.
-- Freeman J. Dyson
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Top Graphic: Portrait of Jacob Mayer, Burgomeister of Basle
(detail) -- Hans Holbein (the Younger) (1497-1543)
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Section 1
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Contents of this Issue (Full reports in Section 2):
Basic Sciences:
1. Ferromagnetism in 1-Dimensional Monatomic Metal Chains
2. On Elementary Excitations in a 1-Dimensional Wire
3. On Quantum Phase Transitions in Ultracold Systems
4. Tides and the Possible Biosphere of Europa
5. On Ultra-Slow and Stored Light Pulses
6. On Supramolecular Chirality
7. Renewed Interest in Systems Biology
8. Immune-System Phagocytes: On the Mechanism of Killing Microbes
9. On the Potassium Ion Channel
10. On the Biodiversity Crisis
11. On the Control of Gene Expression
12. Modulation of Nuclear Shape to Alter Gene Expression
Praxis:
13. On Chemical Control of Phase Stability in Silica/Surfactant
Composites
14. Self-Organized Systems: X-Ray Measurement of Surface Stress
Discontinuities
15. On Entanglement, Decoherence, and Cooper Boxes
16. Molecular Self-Assembly on Metal Substrates
17. Conjugated Polyelectrolytes as Biosensors
18. Organization of 2-Dimensional Phospholipid Monolayers on a
Gel-Forming Substrate
19. HIV Patients in the US: Racial and Ethnic Disparities in
Participation in Research and Access to Experimental Treatments
20. US Homicide Risk During Infancy 1989-1998
21. On Adverse Drug Reactions
22. Frog Deformities Produced by Low Doses of a Herbicide
23. On Dechlorination of Halogenated Organics
24. Discovery of Prions in Mammalian Skeletal Muscle
Miscellany:
25. In Focus: On Thermodynamics and Statistical Physics
26. ScienceWeek Notices and Subscription Information
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Section 2
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1. FERROMAGNETISM IN 1-DIMENSIONAL MONATOMIC METAL CHAINS
In theoretical physics, one approach that has proved to be of
great general utility is to begin with an attempt to identify
and understand the simplest model exhibiting the same essential
features as the physical problem in question. In
condensed-matter physics, such a model is the so-called "Ising
model", an approach that has been applied to ferromagnetism, and
also to a number of other systems. In general, the Ising model
consists of an array of entities in one, two, or three
dimensions, with each entity capable of being in one of two
possible states, with each entity interacting only with its
nearest neighbors, with a condition that when two neighboring
entities are in the same state the total energy of the pair is
reduced compared to when the same two neighboring entities are
in opposite states. These are the elements of the model, with
other conditions imposed depending on how the model is used.
Various versions of the model have been of great utility in
studies of cooperative phenomena in condensed- matter systems.
A "ferromagnet" is a material (e.g., iron) in which there may be
a permanent magnetic moment (magnetic dipole moment), and in
which the *spins of the atoms are aligned parallel to each
other. Concerning permanent magnetic moments: In general,
according to theory, the intrinsic spins of the electrons in an
atom, together with the motion of the electrons around the
nucleus, give rise to a magnetic field around the atom, and the
magnitude of this field is related to the magnetic dipole moment
of the atom or ion. The term "Curie point" refers to the
temperature above which ferromagnetic materials lose their
ferromagnetism. The Curie point is thus the critical point for a
phase transition.
In general, an "epitaxial film" is a crystalline film whose
lattice structure is identical to the lattice structure of an
underlying crystalline substrate.
P. Gambardella et al (Institute of Nanostructure Physics
Lausanne, CH) discuss nanostructure ferromagnetism, the authors
making the following points:
1) Two-dimensional systems, such as ultrathin epitaxial films
and superlattices, display magnetic properties distinct from
bulk materials(1). A challenging aim of current research in
magnetism is to explore structures of still lower
dimensionality(2-5). As the dimensionality of a physical system
is reduced, magnetic ordering tends to decrease as fluctuations
become relatively more important. Spin lattice models predict
that an infinite one-dimensional linear chain with short-range
magnetic interactions spontaneously breaks up into segments with
different orientation of the magnetization, thereby prohibiting
long-range ferromagnetic order at a finite temperature. These
models, however, do not take into account kinetic barriers to
reaching equilibrium or interactions with the substrates that
support the one-dimensional nanostructures.
2) Since the work of Ising (1925), magnetism in 1-dimensional
systems has been the subject of continuous theoretical(4, 5) and
experimental(2) research. Progress in atomic engineering makes
it possible today to build 1-dimensional arrays of
transition-metal chains by self-assembly epitaxial techniques on
suitable substrates. Pioneering experiments in this direction
investigated the magnetic behavior of Fe stripes 1 to 10
nanometers wide obtained by step-flow growth on W(110) and
Cu(111) surfaces. Ideally, one would like to construct monatomic
chains in very large numbers while maintaining a fine control of
the dimensions, uniformity and spatial distribution of the
individual chains.
3) The authors report a demonstration that the existence of both
short- and long-range ferromagnetic order for 1-dimensional
monatomic chains of Co constructed on a Pt substrate. The
authors report evidence that the monatomic chains consist of
thermally fluctuating segments of ferromagnetically coupled
atoms which, below a threshold temperature, evolve into a
ferromagnetic long-range-ordered state owing to the presence of
anisotropy barriers. The Co chains are characterized by large
localized orbital moments and correspondingly large magnetic
anisotropy energies compared to 2-dimensional films and bulk Co.
References (abridged):
1. Schneider, C. M. & Kirschner, J. in Handbook of Surface
Science (eds Horn, K. & Scheffler, M.) 511-668 (Elsevier,
Amsterdam, 2000).
2. Himpsel, F. J., Ortega, J. E., Mankey, G. J. & Willis, R. F.
Magnetic nanostructures. Adv. Phys. 47, 511-597 (1998).
3. Stamm, C. et al. Two-dimensional magnetic particles. Science
282, 449-451 (1998).
4. Weinert, M. & Freeman, A. J. Magnetism of linear chains. J.
Mag. Magn. Mater. 38, 23-33 (1983).
5. Dorantes-Dávila, J. & Pastor, G. M. Magnetic anisotropy of
one-dimensional nanostructures of transition metals. Phys. Rev.
Lett. 81, 208-211 (1998).
Nature 2002 416:301
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2. ON ELEMENTARY EXCITATIONS IN A 1-DIMENSIONAL WIRE
O.M. Auslaender et al (Weizmann Institute of Science, IL)
discuss excitations in a 1-dimensional wire, the authors making
the following points:
1) Electronic systems such as metals contain a vast number of
mobile electrons. Surprisingly, despite the Coulomb repulsion
between them, many electronic properties of metals can be well
described in terms of independent particles with a finite
lifetime, each carrying charge e and spin half (1, 2). Most
importantly, their excitation spectrum, which for noninteracting
electrons is simply determined by the underlying band mass m, is
only slightly modified by the Coulomb interactions. However,
such a simple description of electronic systems, known as Landau
Fermi-liquid theory (1), is valid only in two and three spatial
dimensions. In one-dimensional (1D) metals, where electrons are
forced to move on a line, the single-particle description
completely breaks down by even the slightest Coulomb repulsion.
Instead, the excitations of an interacting 1D system, being
fluctuations of the charge and spin densities, are well
described by collective modes that involve the entire electron
population (3). These collective modes are decoupled into two
separate kinds: collective spin modes and collective charge
modes. Coulomb interactions couple primarily to the latter,
thereby strongly influencing their dispersion. Conversely, the
excitation spectrum of the spin modes, typically unaffected by
interactions, remains similar to the noninteracting case. It can
be shown that the stronger the Coulomb repulsion is, the larger
the propagation velocity is.
2) Although interactions fundamentally alter the excitation
spectrum of a 1D wire, they do not affect its conductance (5).
In fact, a clean 1D wire has universal conductance irrespective
of its length, density, and dispersion, rendering transport
measurements an ineffective tool for investigating the role of
interactions in one dimension. This limitation can be
circumvented by studying the temperature-dependent transport
properties of disordered wires. However, the lack of knowledge
of the nature of the disorder potential often restricts the
interpretation of such experiments. Therefore, the most direct
way to explore the role of interactions in one dimension is to
measure the excitation spectrum itself.
3) The authors report a method for experimentally determining
the complete dispersion relations of the collective elementary
excitations of an interacting 1D system, in which the tunneling
conductance between two clean, parallel wires is measured. A
fixed amount of energy and momentum is supplied to the system by
externally applying a bias between the wires and a magnetic
field perpendicular to their plane. Because of the conservation
of energy and momentum in this geometry, tunneling is forbidden
unless there exist elementary excitations that match the
supplied momentum and energy. The excitation spectrum deviates
from the noninteracting spectrum, attesting to the importance of
Coulomb interactions. An observed 30% enhancement of the
excitation velocity relative to noninteracting electrons with
the same density, a parameter determined experimentally, is
consistent with theories on interacting electrons in one
dimension. In short wires, 6 and 2 micrometers long, finite size
effects, resulting from the breaking of translational
invariance, are observed.
References (abridged):
1. P. Nozieres, Theory of Interacting Fermi Systems, The
Advanced Book Program (Addison-Wesley, Reading, MA, ed. 2, 1997).
2. B. L. Altshuler, A. G. Aronov, in: Electron-Electron
Interaction in Disordered Systems, A. L. Efros, M. Pollak, Eds.
(North-Holland, Amsterdam, 1985), pp. 1-153.
3. V. J. Emery, in: Highly Conducting One-Dimensional Solids, J.
T. Devreese, R. P. Evrard, V. E. van Doren (Plenum, New York,
1979), pp. 247-303.
4. D. Yue, L. I. Glazman, K. A. Matveev, Phys. Rev. B 49, 1966
(1994) [CrossRef][ISI].
5. Y. Oreg, A. M. Finkel'stein, Phys. Rev. B 54, R14265 (1996).
Science 2002 295:825
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3.ON QUANTUM PHASE TRANSITIONS IN ULTRACOLD SYSTEMS
M. Greiner et al (Ludwig-Maximilians University Munich, DE)
discuss quantum phase transitions, the authors making the
following points:
1) A physical system that crosses the boundary between two
phases changes its properties in a fundamental way. It may, for
example, melt or freeze. This macroscopic change is driven by
microscopic fluctuations. When the temperature of the system
approaches zero, all thermal fluctuations die out. This
prohibits phase transitions in classical systems at zero
temperature, as their opportunity to change has vanished.
However, their quantum mechanical counterparts can show
fundamentally different behavior. In a quantum system,
fluctuations are present even at zero temperature, due to
Heisenberg's uncertainty relation. These quantum fluctuations
may be strong enough to drive a transition from one phase to
another, bringing about a macroscopic change.
2) A prominent example of such a quantum phase transition is the
change from the superfluid phase to the Mott insulator phase in
a system consisting of bosonic particles with repulsive
interactions hopping through a lattice potential. This system
was first studied theoretically in the context of
superfluid-to-insulator transitions in liquid helium(1).
Recently, Jaksch et al (2) have proposed that such a transition
might be observable when an ultracold gas of atoms with
repulsive interactions is trapped in a periodic potential. To
illustrate this idea, the authors consider an atomic gas of
bosons at low enough temperatures that a Bose–Einstein
condensate is formed. The condensate is a superfluid, and is
described by a wavefunction that exhibits long-range phase
coherence(3). An intriguing situation appears when the
condensate is subjected to a lattice potential in which the
bosons can move from one lattice site to the next only by tunnel
coupling. If the lattice potential is turned on smoothly, the
system remains in the superfluid phase as long as the atom–atom
interactions are small compared to the tunnel coupling. In this
regime a delocalized wavefunction minimizes the dominant kinetic
energy, and therefore also minimizes the total energy of the
many-body system. In the opposite limit, when the repulsive
atom–atom interactions are large compared to the tunnel
coupling, the total energy is minimized when each lattice site
is filled with the same number of atoms. The reduction of
fluctuations in the atom number on each site leads to increased
fluctuations in the phase. Thus in the state with a fixed atom
number per site phase coherence is lost. In addition, a gap in
the excitation spectrum appears. The competition between two
terms in the underlying hamiltonian (here between kinetic and
interaction energy) is fundamental to quantum phase
transitions(4) and inherently different from normal phase
transitions, which are usually driven by the competition between
inner energy and entropy.
References (abridged):
1. Fisher, M. P. A., Weichman, P. B., Grinstein, G. & Fisher, D.
S. Boson localization and the superfluid-insulator transition.
Phys. Rev. B 40, 546-570 (1989).
2. Jaksch, D., Bruder, C., Cirac, J. I., Gardiner, C. W. &
Zoller, P. Cold bosonic atoms in optical lattices. Phys. Rev.
Lett. 81, 3108-3111 (1998).
3. Stringari, S. Bose-Einstein condensation and superfluidity in
trapped atomic gases. C.R. Acad. Sci. 4, 381-397 (2001).
4. Sachdev, S. Quantum Phase Transitions (Cambridge Univ. Press,
Cambridge, 2001).
Nature 2002 415:39
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4. TIDES AND THE POSSIBLE BIOSPHERE OF EUROPA
It is an irony that although the term "living system" is widely
used in science, the term has no consensus definition. Instead,
there are many definitions: physiological, biochemical, genetic,
metabolic, thermodynamic, and so on. One might think the
question of the definition of "life" is only of philosophical
significance, but if you are designing a robot to search for
"life" on another astronomical body, precisely what is the robot
to search for? At the present time, the answer to this question
is not at all clear.
Concerning definitions, the various definitions of "life"
currently in use can in general be summarized as follows:
1) The physiological definition defines a living system as a
system that performs various functions such as eating,
metabolizing, excreting, breathing, moving, growing,
reproducing, and being responsive to external stimuli.
2) The biochemical definition defines a living system as a
system that contains reproducible hereditary information coded
in nucleic acids and that metabolizes by controlling the rate of
chemical reactions with protein catalysts (enzymes).
3) The genetic definition defines a living system as a system
capable of evolution by natural selection.
4) The metabolic definition defines a living system as a system
with a definite boundary, the system continually exchanging some
of its materials with its surroundings, but the exchange not
altering the general properties of the system, at least over
some period of time.
5) The thermodynamic definition defines a living system as an
open system manifesting a local increase in order (decrease in
entropy) at the expense of a larger decrease in order outside
the system.
Of course, physical scientists can immediately think of many
"non-living" physical systems that can be described by one or
more of the above definitions, but biologists are fully aware of
such counter-examples and admit the ambiguities of all the
definitions. Research on Earth-bound living systems goes on,
ambiguity or no ambiguity, but when the focus is a search for
living systems elsewhere, the ambiguities become critical.
Jupiter's satellite system consists of at least 16 moons, the
four largest of which are called the Galilean moons, since they
were discovered by Galileo Galilei (1564-1642). They are Io,
Europa, Ganymede, and Callisto, in order of their orbital
distance from Jupiter. Europa, which is slightly smaller than
Earth's moon, has a thick icy crust, and may also have a liquid
water mantle beneath this crust. Very few craters are present on
Europa, which suggests an active surface that renews itself and
thus erases craters as fast as they form from impacts. The
surface also shows numerous lines about 30 kilometers wide and
1000 kilometers long, and these have been interpreted to be
breaks in the crust where water from below has refrozen. The
possible existence of a liquid water mantle beneath the ice on
Europa is of great interest to planetary scientists, since such
a mantle might contain life forms.
Richard Greenberg (University of Arizona, US) discusses the
Jovian moon Europa, the author making the following points:
1) Although the Copernican revolution began over 500 years ago
with the realization that the Earth was not the center of the
universe, but we still await its grand finale: the anticipated
discovery of life elsewhere. Where else might we find life? The
vast scale of the universe makes it virtually certain that there
are other Earth-like settings. In our own Solar System, the
distance of Mars from the Sun makes it sufficiently Earth-like
that, especially with increasing evidence for occasional liquid
water, many are looking there for the first signs of
extraterrestrial life. Recently, however, a new contender has
emerged, and surprisingly it is from the cold outer Solar
System: it is Jupiter's moon Europa.
2) Europa played an early role in the Copernican revolution as
well. As one of the four satellites of Jupiter discovered by
Galileo in 1610, Europa provided evidence that objects could
orbit a celestial body other than Earth. Its steady motion
around the planet, observable in the smallest backyard
telescope, has been followed ever since. However, it was not
until 20 years ago that scientists realized that the tidal
stresses imposed on Europa by the giant Jupiter could generate
enough heat to maintain water in a liquid state, even so far
from the Sun.
3) The possibility of liquid water opened the door to
speculation about life, but water alone is not sufficient to
sustain organisms. Life requires a nurturing environment,
appropriate chemistry, a source of energy — a habitat. Now,
late-20th-century observations by another Galileo — this time
the Galileo spacecraft in orbit around Jupiter — show that tidal
processes may create physical conditions that support a variety
of interconnected habitable settings.
4) Planetary scientists have known for decades that Europa's
surface is predominantly water ice, beginning with ground-based
spectroscopic studies by Gerard Kuiper, among others. The
density inferred from gravity measurements suggests that the
water layer may extend down as far as 150 kilometers below the
surface, or somewhat less if part of the low-density layer is
clay under the ocean. Although the surface is frozen, below it
most of the water layer is probably liquid.
Even a distant view of Europa shows the two main types of
geological terrain: Lines represent tectonic features, such as
cracks and rifts and ridges, and splotches represent disrupted,
chaotic terrain. In fact, nearly all of Europa is covered by
either tectonic or chaotic terrain, in roughly equal measure.
Both appear to have been formed by processes driven by tides:
Over the 85-hour day on Europa, tidal distortion creates stress
that correlates well with tectonic features. And the chaos
likely results from modest local and regional concentration of
the tremendous internal heat of tidal friction.(1-3)
References (abridged):
1. Chyba, C. F., and C. B. Phillips. 2001. Possible ecosystems
and the search for life on Europa. Science 98:801-804.
2. Greenberg, R., P. Geissler, B. R. Tufts and G. V. Hoppa.
2000. Habitability of Europa's crust: The role of tidal-tectonic
processes. Journal of Geophysical Research 105(E7):17,551-17,561.
3. Greenberg, R., G. V. Hoppa, B. R. Tufts, P. Geissler, J.
Riley and S. Kadel. 1999. Chaos on Europa. Icarus 141:263-286.
American Scientist 2002 90:48
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5. ON ULTRA-SLOW AND STORED LIGHT PULSES
An experimental "light pulse" has a finite duration, and in
theory (the so-called "bandwidth theorem") this requires an
infinite number of waves of different frequency to be added
together. The shorter the desired pulse, the larger the
bandwidth of frequencies that must be used. Theoretically, all
light pulses are therefore formed by a packet of waves of
different frequency, each of which has a different amplitude and
phase. The speed of individual waves is called the "phase
velocity", and the velocity at which the peak of the wave packet
propagates is called the "group velocity". In a vacuum, the
phase and group velocities are identical, but in a highly
absorbing or dispersive medium the phase and group velocities
are usually different.
Experiments involving the control of light pulses in a quantum
mechanical regime hold great promise for a future technology of
quantum computing involving optical information storage and
transmission. In 1999, L.V. Hau et al succeeded in slowing light
to a velocity of 30 meters per second in an ultracold sodium
gas. In 2001, the same laboratory reported effectively stopping
light completely for an interval of 1 millisecond before
releasing the pulse to resume normal velocity. Essentially, the
phenomenon involves "storing" the light pulse in the quantum
states of the atoms, with the light pulse reconstituted for
propagation at a later time.
A.V. Turukhin et al (Massachusetts Institute of Technology, US)
discuss slowed light pulses, the authors making the following
points:
1) Since the first observations of ultraslow light (1,2), there
has been substantial interest in its potential applications. For
example, it was proposed that slowing the group velocity of a
laser pulse down to the speed of sound in a material can produce
strong coupling between acoustic waves and the electromagnetic
field (3). This might be utilized for efficient multiwave mixing
and quantum nondemolition measurements (4), as well as for novel
acousto-optical devices. Ultraslow light might even allow
nonlinear interactions down to a single photon level (5).
Finally, it has been suggested and experimentally demonstrated
that the group velocity of light can be decelerated to zero,
effectively trapping or "stopping" the light pulse. Light stored
by this technique is potentially important for quantum computing
applications because it is relatively easy to implement and can
be accomplished with near 100% fidelity in principle.
2) For many potential applications of slow light, a solid-state
medium is preferred. However, most solid materials have
relatively broad optical linewidths, which limits the achievable
light-speed reduction. A notable exception to this general rule
is a class of materials consisting of rare-earth doped
insulators that exhibit spectral hole burning. These materials
are generally used for ultrahigh density optical memories and
processors. In one such material, Pr doped Y(sub2)SiO(sub5)
(Pr:YSO), efficient, narrow-linewidth electromagnetically
induced transparency has also been demonstrated. This is
significant because narrow band electromagnetically induced
transparency enabled the demonstration of ultraslow and
"stopped" light in atomic vapors.
3) The authors report ultraslow group velocities of light in an
optically dense crystal of Pr doped Y(sub2)SiO(sub5). Light
speeds as slow as 45 meters per second were observed,
corresponding to a group delay of 66 microseconds. Deceleration
and "stopping" or trapping of the light pulse was also observed.
These reductions of the group velocity are accomplished by using
a sharp spectral feature in absorption and dispersion that is
produced by resonance Raman excitation of a ground-state spin
coherence.
References (abridged):
1. L. V. Hau, S. E. Harris, Z. Dutton, and C. Behroozi, Nature
(London) 397, 594 (1999).
2. M. Kash, V. Sautenkov, A. Zibrov, L. Hollberg, G. Welch, M.
Kukin, Y. Rostovsev, E. Fry, and M. Scully, Phys. Rev. Lett. 82,
5229 (1999).
3. A. Matsko, Y. Rostovtsev, H. Cummins, and M. Scully, Phys.
Rev. Lett. 84, 5752 (2000).
4. V. Braginsky and F. Khalili, Quantum Measurement (Cambridge
University Press, Cambridge, United Kingdom, 1992).
5. M. Lukin and A. Imamoglu, Phys. Rev. Lett. 84, 1419 (2000).
Phys. Rev. Lett. 2002 88:023602
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6. ON SUPRAMOLECULAR CHIRALITY
M-J. Kim et al (Kwang-Ju Institute of Science and Technology,
KR) discuss supramolecular chirality, the authors making the
following points:
1) Fundamental questions concerning chiroptical polymers arise
from the characteristics of natural polymers, which have a
one-handed helical conformation and show characteristic
functionality in living systems.(1) Conformational chirality can
be optically induced by the irradiation of photochromic
molecules and polymers.(2-5) This phenomenon has been
investigated for cases of many kinds of photochromophores, for
example, azobenzenes,(2-4) overcrowded alkenes,(5) diarylethens,
binaphthalenes, and spiropyranes.
2) Since the pioneering studies by Goodman (1967), the optical
induction of supramolecular chirality has been widely studied
using azobenzene-containing polymers. Azobenzenes are well-known
chromophores for their photoinduced linear orientation via trans
— cis — trans photoisomerization. Photoinduced chirality changes
in azopolymers have been reported for polymethacrylates,(2)
polypeptides,(3) and polyisocyanates.(4) These azobenzene
polymers contain chiral centers, and the chiral properties were
investigated in solution using two different wavelengths as the
light source.
3) The use of circularly polarized light has been demonstrated
as a method for partially resolving a racemic mixture. Recently,
Nikolova et al (1997) reported on the photoinduced chirality of
amorphous and liquid crystalline azobenzene polymers by
irradiation with circularly polarized light. The induced
chirality of the azobenzene polymers was investigated as a
function of the ellipticity of incident light. However, Iftime
et al (2000) reported that circular dichroism is not induced in
an amorphous azopolymer film by irradiation with circularly
polarized light and proposed that liquid crystalline alignment
represents one of the key factors in the creation of a chiral
superstructure. Therefore, the issue of the origin of the
photoinduced chirality of azobenzene polymer films irradiated by
light with handedness is not clear.
4) The authors report an investigation of chirality
photoinduction from amorphous and achiral azobenzene polymer
films. The suggest their results demonstrate that liquid
crystallinity is not a necessary condition for a material to
exhibit photoinduced chiral properties.
References (abridged):
1. Circular Dichroism Principles and Applications, 2nd ed.;
Berova, N., Nakanishi, K., Woody, R. W., Eds.; Wiley-VCH, Inc.:
New York, 2000.
2. Angiolini, L.; Caretti, D.; Giorgini, L.; Salatelli, E.
Macromol. Chem. Phys. 2000, 207, 533.
3. Pieroni, 0.; Fissi, A.; Ciardelli, F. React. Fund. Polvm.
1995, 6, 185.
4. Muller, M.; Zentel, R. Macromolecules 1996, 29, 1609.
5. Feringa, B. L.; Jager, W. F.; Lange B. d. J. Am. Chem. Soc.
1991, 113, 5468.
J. Am. Chem. Soc. 2002 124:3504
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7. RENEWED INTEREST IN SYSTEMS BIOLOGY
The mathematician Norbert Weiner (1894-1964) established the
science of "cybernetics", a field concerned with the common
factors of control and communication in living organisms,
automatic machines, and organizations. In 1948, Weiner's book
_Cybernetics: or, Control and Communication in the Animal and
the Machine_ appeared. The book was extremely popular, and
Wiener became known in the broader scientific community. His
ideas were influential in a reformulation of organismal biology
into "systems biology", which has had parallel development in
various places, the phrase meaning different things to different
people, but in general implying the application of control
systems analysis to living systems.
Hiroaki Kitano (Sony Computer Science Laboratories, JP)
discusses systems biology, the author making the following
points:
1) Since the days of Norbert Weiner, system-level understanding
has been a recurrent theme in biological science (1). The major
reason it is gaining renewed interest today is that progress in
molecular biology, particularly in genome sequencing and
high-throughput measurements, enables us to collect
comprehensive data sets on system performance and gain
information on the underlying molecules. This was not possible
in the days of Weiner, when molecular biology was still an
emerging discipline. There is now a golden opportunity for
system-level analysis to be grounded in molecular-level
understanding, resulting in a continuous spectrum of knowledge.
2) System-level understanding, the approach advocated in systems
biology (2), requires a shift in our notion of "what to look
for" in biology. While an understanding of genes and proteins
continues to be important, the focus is on understanding a
system's structure and dynamics. Because a system is not just an
assembly of genes and proteins, its properties cannot be fully
understood merely by drawing diagrams of their interconnections.
Although such a diagram represents an important first step, it
is analogous to a static roadmap, whereas what we really seek to
know are the traffic patterns, why such traffic patterns emerge,
and how we can control them.
3) Identifying all the genes and proteins in an organism is like
listing all the parts of an airplane. While such a list provides
a catalog of the individual components, by itself it is not
sufficient to understand the complexity underlying the
engineered object. We need to know how these parts are assembled
to form the structure of the airplane. This is analogous to
drawing an exhaustive diagram of gene-regulatory networks and
their biochemical interactions. Such diagrams provide limited
knowledge of how changes to one part of a system may affect
other parts, but to understand how a particular system
functions, we must first examine how the individual components
dynamically interact during operation. We must seek answers to
questions such as: What is the voltage on each signal line? How
are the signals encoded? How can we stabilize the voltage
against noise and external fluctuations? And how do the circuits
react when a malfunction occurs in the system? What are the
design principles and possible circuit patterns, and how can we
modify them to improve system performance?
4) In summary: To understand biology at the system level, we
must examine the structure and dynamics of cellular and
organismal function, rather than the characteristics of isolated
parts of a cell or organism. Properties of systems, such as
robustness, emerge as central issues, and understanding these
properties may have an impact on the future of medicine.
However, many breakthroughs in experimental devices, advanced
software, and analytical methods are required before the
achievements of systems biology can live up to their much-touted
potential.
References (abridged):
1. N. Weiner, Cybernetics or Control and Communication in the
Animal and the Machine (MIT Press, Cambridge, MA, 1948).
2. H. Kitano, Foundations of Systems Biology (MIT Press,
Cambridge, MA, 2001).
Science 2002 295:1662
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8. IMMUNE-SYSTEM PHAGOCYTES: ON THE MECHANISM OF KILLING MICROBES
The immune system blood cells called "neutrophils" have a
diameter between 12 and 15 microns, and the nucleus of these
cells consists of two to five lobes joined together by thin
filaments. Neutrophils move by means of amoeboid motion, and the
same processes are involved in the engulfment (phagocytosis) of
microbes. The bone marrow of a normal adult human produces
approximately 100 billion neutrophils per day.
Chronic granulomatous disease is a congenital defect involving
polymorphonuclear leukocytes (e.g., neutrophils), the disorder
producing an increased susceptibility to severe infection by
catalase-positive microorganisms. Inheritance is usually
autosomal recessive or X-linked.
E.P. Reeves et al (University College London, UK) discuss the
action of immune-system phagocytes, the authors making the
following points:
1) Elie Metchnikoff (1845-1916) discovered that 'phagocytes'
confer immunity by engulfing invading microbes(1). It was
supposed that killing was effected by the contents of the
cytoplasmic granules released into the phagocytic vacuoles in
which the microbes were encapsulated. This hypothesis was
supplanted(2, 3) by the supposition that the killing agents were
reactive oxygen species(4, 5), supported by the discovery of
chronic granulomatous disease, a human condition characterized
by profound susceptibility to bacterial and fungal infection.
The finding that phagocytes from these individuals are unable to
generate reactive oxygen species or to kill microbes efficiently
was taken to imply that the respiratory burst promotes killing
by generating toxic superoxide(4, 5) and H(sub2)O(sub2). The
H(sub2)O(sub2) was thought also to exert an indirect effect,
acting as substrate for myeloperoxidase-catalysed halogenation.
2) According to this prevailing reactive oxygen species model, a
lack of proteases should not affect the killing ability of
neutrophils. Although earlier studies had shown a requirement
for neutrophil elastase to kill some Gram-negative bacilli, and
for both cathepsin G and elastase to protect against infection
by Aspergillus fumigatus, the authors report they extended these
observations to Staphylococcus aureus, the commonest cause of
infection in chronic granulomatous disease, and to Candida
albicans, a microbe that was thought could be killed only with
the intervention of oxygen-dependent processes, because mice
lacking myeloperoxidase are abnormally sensitive to this
pathogen.
The authors report that the simple reactive oxygen species
scheme, which for many years has served as a satisfactory
working hypothesis, is inadequate. The authors report that mice
made deficient in neutrophil-granule proteases but normal with
respect to superoxide production and iodinating capacity, are
unable to resist staphylococcal and candidal infections. The
authors also demonstrate that activation provokes the influx of
an enormous concentration of reactive oxygen species into the
endocytic vacuole. The resulting accumulation of anionic charge
is compensated by a surge of K+ ions that cross the membrane in
a pH-dependent manner. The consequent rise in ionic strength
engenders the release of cationic granule proteins, including
elastase and cathepsin G, from the anionic sulphated
proteoglycan matrix. The authors demonstrate that it is the
proteases, thus activated, that are primarily responsible for
the destruction of the bacteria.
References (abridged):
1. Metchnikoff, B. Immunity in Infective Diseases (Cambridge
Univ. Press, 1905).
2. Sbarra, A. J. & Karnovsky, M. L. The biochemical basis of
phagocytosis. 1. Metabolic changes during the ingestion of
particles by polymorphonuclear leukocytes. J. Biol. Chem. 234,
1355-1362 (1959).
3. Mandell, G. L. Bactericidal activity of aerobic and anaerobic
polymorphonuclear neutrophils. Infect. Immun. 9, 337-341 (1974).
4. Babior, B. M., Curnutte, J. T. & Kipnes, R. S. Biological
defense mechanisms. Evidence for the participation of superoxide
in bacterial killing by xanthine oxidase. J. Lab. Clin. Med. 85,
235-244 (1975).
5. Babior, B. M., Kipnes, R. S. & Curnutte, J. T. Biological
defence mechanisms: the production by leukocytes of superoxide,
a potential bactericidal agent. J. Clin. Invest. 52, 741-744
(1973).
Nature 2002 416:291
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9. ON THE POTASSIUM ION CHANNEL
The functional electrical activity of nerve cells is based
essentially on the rapid movements of ions across the membranes
of these cells, especially the movements of sodium and potassium
ions. These ion movements occur through special pores ("ion
channels") in the cell membrane, and one of the important
problems during the past few decades has been to characterize
these ion channels at the molecular level. Most ion channels are
selective, allowing only ions of a certain type to pass, and an
individual cell has ion channels with various ion selectivities.
The selectivity of an ion channel can be "gated", the channel
effectively opened or closed, and ion channels are said to
"voltage-gated" or "ligand-gated", depending on how the change
in selectivity is provoked. The term "voltage-gated" refers to
the opening or closing of an ion channel by changes in the
electrical potential across the membrane, while the term
"ligand-gated" refers to opening and closing of an ion channel
by interactions between ligands and membrane receptors. It has
become apparent that voltage-gated ion channels are
transmembrane proteins consisting of 4 identical subunits, each
of which contains 6 transmembrane segments. Studies of the
potassium ion channel have identified two segments that contain
several charged protein residues, and these charged residues
apparently sense changes in the potential difference across the
membrane and form part of the membrane "voltage sensor".
Although these regions apparently undergo conformational changes
in response to changes in membrane potential, little is known
about the nature of these changes.
M.S. Sansom and I.H. Shrivastava (University of Oxford, UK)
discuss the potassium ion channel, the authors making the
following points:
1) When the crystal structure of the bacterial channel protein
KcsA was first solved in 1998(1) , it provided us with our first
view of an ion channel at atomic resolution. The structure,
determined at the relatively modest resolution of 3.2 angstroms,
revealed the basic architecture of the channel: an extracellular
selectivity filter, a central cavity and an intracellular gate.
The importance of KcsA lies in the conservation of this basic
pore structure between KcsA and other classes of K+ channels
found in a wide range of organisms, including humans(2) . If we
can understand ion permeation in KcsA, we will thus have grasped
the fundamental mechanism of all K+ channels. But, despite a
large body of work stimulated by the earlier KcsA structure,
fundamental permeation studies were hampered by its limited
resolution.
2) New studies have extended the resolution of the KcsA
structure to 2.0 angstroms, making ions and water molecules in
the filter clearly visible(3) . Changes in structure in the
presence of a low concentration of K+ ions, and in the pattern
of ion occupancy when Rb+ ions are substituted for K+(4) , have
also been explored. These results have been combined with
electrophysiological studies of the flux of K+ versus Rb+ ions
through KcsA as a function of ionic concentration(4) . And
detailed calculations have been made of the energetics of ion
permeation through the KcsA filter(5) . Together, these new
results provide a detailed and convincing picture of the
mechanism of high throughput K+ flux — about one ion every 10
nanoseconds — through K channels. Significantly, these
higher-resolution structural studies confirm a number of
predictions from earlier simulation studies, indicating that
simulations can indeed provide new information.
3) Attempts to understand the high-throughput permeation
mechanism of KcsA have combined electrophysiological
measurements on channels reconstituted in artificial lipid
bilayers with x-ray studies of KcsA crystals in the presence of
different concentrations of K+ or Rb+ ions. Fine details of ions
and water molecules in the filter have now been revealed by the
high resolution structure of KcsA(3).
References (abridged):
1. Doyle D.A., Cabral J.M., Pfuetzner R.A., Kuo A., Gulbis J.M.,
Cohen S.L., Cahit B.T. and MacKinnon R. (1998) The structure of
the potassium channel: molecular basis of K+ conduction and
selectivity. Science, 280:69-77.
2. Lu Z., Klem A.M. and Ramu Y. (2001) Ion conduction pore is
conserved among potassium channels. Nature, 413:809-813.
3. Zhou Y., Morais-Cabral J.H., Kaufman A. and MacKinnon R.
(2001) Chemistry of ion coordination and hydration revealed by a
K+ channel-Fab complex at 2.0 Ĺ resolution. Nature, 414:43-48.
4. Morais-Cabral J.H., Zhou Y. and MacKinnon R. (2001) Energetic
optimization of ion conduction by the K+ selectvity filter.
Nature, 414:37-42.
5. Bernčche S. and Roux B. (2001) Mechanism of ions permeation
in the KcsA potassium channel. Biophys. J., 80:175a.
Current Biology 2002 12:R65
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10. ON THE BIODIVERSITY CRISIS
P.S. Levin and D.A. Levin (National Marine Fisheries Service,
US) discuss the biodiversity crisis, the authors making the
following points:
1) Some 2,000 species of Pacific Island birds (about 15 percent
of the world total) have gone extinct since human colonization.
Roughly 20 of the 297 known mussel and clam species and 40 of
about 950 fishes have perished in North America in the past
century. On average, one extinction happens somewhere on earth
every 20 minutes. Ecologists estimate that half of all living
bird and mammal species will be gone within 200 or 300 years.
Although crude and occasionally controversial, such statistics
illustrate the extent of the current upheaval, which spans the
globe and affects a broad array of plants and animals.
2) Species extinctions are, of course, perfectly natural. In the
grand drama of geologic time, paleontologists have seen
countless species enter and exit the stage. All species begin in
some restricted setting and then spread. Most subsequently
undergo differentiation, and eventually all species come to an
end. The diversity of species at any point in time is simply the
result of these ongoing processes, which can wax and wane in
intensity. For the most part, the total number of species
inhabiting the Earth probably remains fairly static.
3) The current losses are, however, exceptional. Rates of
extinction appear now to be 100 to 1,000 times greater than
background levels, qualifying the present as an era of "mass
extinction." The globe has experienced similar waves of
destruction just five times in the past. Devastating as they
were, after each of these mass extinctions, biological diversity
ultimately recovered. The time it took varied among taxonomic
groups and also depended on just where the organisms lived.
General recovery probably required a few million years in each
case.
References (abridged):
1. Hallam, A, and P. B. Wignall. 1997. Mass Extinctions and
Their Aftermath. Oxford: Oxford University Press.
2. Levin, D. A. 2000. The Origin, Expansion, and Demise of Plant
Species. New York: Oxford University Press.
3. Rosenzweig, M. L. 2001. Loss of speciation rate will
impoverish future diversity. Proc. Nat. Acad. Sci. 98:5404-5410.
American Scientist 2002 90:6
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11. ON THE CONTROL OF GENE EXPRESSION
A.H. Brivanlou and J.E. Darnell Jr. (Rockefeller University, US)
discuss the control of gene expression, the authors making the
following points:
1) All cellular life can recognize and properly respond to
molecules in the extracellular environment. Indeed, an increased
repertoire of recognized extracellular signaling molecules
matched with increasingly sophisticated intracellular responses
was the central requirement for the evolution of metazoan life.
Two very broad fields of research, which are often described as
"signal transduction" and "control of gene expression," have
merged recently to become a pivotal arena for developmental
genetics as well as cellular biochemistry.
2) A host of proteins crucial to transcription initiation are
assembled into the RNA polymerase, the general transcription
factors, coactivators, corepressors, chromatin remodelers,
histone acetylases, deacetylases, kinases, and methylases, to
list the main participants (1-5). These crucial proteins are
present in all eukaryotic cells and contribute to the initiation
of every RNA polymerase II primary transcript that eventually
becomes messenger RNA.
3) As important as the approximately 200 to 300 proteins that
constitute the coactivators and the transcriptional machinery
may be to the survival of cells and organisms, the regulation of
the choice of specific initiation sites for transcription is not
vested in these proteins. Rather, transcriptional regulation
depends on members of an even larger number of proteins, in
mammals perhaps 2000 to 3000, with two characteristic domains: a
DNA binding domain that binds gene-specific regulatory sites
directly, and a second domain that exhibits transcriptional
activation potential. In some cases this dual requirement is
shared between partner proteins, so that the site-specific
binding domain and transcription activation domain occur on
separate proteins. These site-specific transcription factors
recruit coactivators and the transcription machinery to initiate
gene-specific transcription (1-5). As development and cell
specialization occurs, selection among these 2000+ transcription
factors for the regulation of cell-specific gene expression
involves (i) a cascade of transcriptional control of
transcription factor genes, and (ii) signals from outside the
cell that activate, posttranscriptionally, already formed
transcription factors. In the regulatory regions in the DNA of a
few well-studied vertebrate genes, as many as six to eight
different protein chains, acting on one enhancer (together
forming an "enhanceosome"), are required for gene-specific
regulation, and this is likely true for many other genes. The
combinatorial use of subsets of the 2000+ proteins could easily
mean that the complete set of regulators for each gene is
unique, ensuring the right amount of the right protein at the
right time as development proceeds.
References (abridged):
1. S. Malik and R. G. Roeder, Trends Biochem. Sci. 25, 277 (2000)
2. A. M. Naar, B. D. Lemon, R. Tjian, Annu. Rev. Biochem. 70,
475 (2001)
3. A. M. Naar, S. Ryu, R. Tjian, Cold Spring Harbor Symp. Quant.
Biol. 63, 189 (1998)
4. K. A. Jones and J. T. Kadonaga, Genes Dev. 14, 1992 (2000)
5. T. Jenuwein and C. D. Allis, Science 293, 1074 (2001)
Science 2002 295:813
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12. MODULATION OF NUCLEAR SHAPE TO ALTER GENE EXPRESSION
A "keratinocyte" is a cell of the living epidermis and certain
oral epithelium that produces keratin in the process of
differentiating into the dead and fully keratinized cells of the
outer layer of skin (stratum corneum).
C.H. Thomas et al (Northwestern University, US) discuss
modulation of nuclear shape and gene expression, the authors
making the following points:
1) Cell morphology has a profound effect on a range of cellular
events, such as proliferation (1-3), differentiation (4-5),
cytoskeletal organization, and presumably gene expression.
Changes to the cytoskeleton lead to altered stress levels
imparted on the nucleus and could affect organelle and DNA
organization and distribution, ultimately altering cell
function. For example, the rate of albumin secretion from
hepatocytes can be altered by constraining cell size on
patterned culture surfaces (3). In human epidermal keratinocytes
cell shape can modulate between terminal differentiation and
proliferation (4). Furthermore, cells can be forced to enter the
apoptotic cascade when the area on which the cell is allowed to
spread is constrained (1). One proposed mechanism for the
transduction of cell shape information into gene expression is
through mechanical forces transmitted by means of the direct
link of the cytoskeleton to the nucleus, and in particular to
nuclear matrix proteins.
2) The authors report a method for investigating gene-specific
responses in individual cells with controlled nuclear shape and
projected area. The shape of the nuclei of primary osteogenic
cells were controlled on microfabricated substrata with
regiospecific chemistry by confining attachment and spreading of
isolated cells on adhesive islands. Gene expression and protein
synthesis were altered by changing nuclear shape. The authors
suggest their data support the concept of gene expression and
protein synthesis based on optimal distortion of the nucleus,
possibly altering transcription factor affinity for DNA,
transport to the nucleus, or nuclear matrix organization. The
authors suggest that the combination of microfabricated
surfaces, reverse transcription in situ PCR, and a nuclear shape
index measurement is an excellent system to study how
transcription factors, the nuclear matrix, and the cytoskeleton
interact to control gene expression and may be useful for
studying a wide variety of other cell shape-gene expression
relationships.
References (abridged):
1. Chen, C. S. , Mrksich, M. , Huang, S. , Whitesides, G. M. &
Ingber, D. E. (1997) Science 276, 1425-1428
2. Folkman, J. & Moscona, A. (1978) Nature (London) 273, 345-349
3. Singhvi, R. , Kumar, A. , Lopez, G. P. , Stephanopoulos, G.
N. , Wang, D. I. C. , Whitesides, G. M. & Ingbar, D. E. (1994)
Science 264, 696-698
4. Watt, F. M. , Jordan, P. W. & O'Neil, C. H. (1988) Proc.
Natl. Acad. Sci. USA 85, 5576-5580
5. Aulthouse, A. L. (1994) Anat. Rec. 238, 31-37
Proc. Nat. Acad. Sci. 2002 99:1972
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13. ON CHEMICAL CONTROL OF PHASE STABILITY IN SILICA/SURFACTANT
COMPOSITES
A.F. Gross et al (University of California Los Angeles, US)
discuss control of phase stability, the authors making the
following points:
1) Activation energies represent the quantity of energy
necessary to overcome a barrier to reach a new chemical or
physical state. Usually, solution-phase chemistry cannot be
utilized to modify activation energies for crystalline solids
because chemically altering the sample also changes the crystal
phase of the material. However, in materials such as
silica/surfactant composites (MCM-41-type materials), it is
possible to hydrothermally modify the atomic scale amorphous
silica framework without changing the nanoscale periodicity of
the composite.(1-5) Careful examination of the nanometer scale
architecture, however, shows that these atomic scale changes do
influence the nanoscale structure in subtle ways.(3,4) If these
inorganic/organic composite materials undergo a rearrangement of
the nanometer scale periodicity after chemical framework
alteration, they can show markedly different transformation
kinetics.(3) By controlling the possible chemical reactions in
the transforming material and observing the effect on activation
energies, one is thus able to identify the experimental
variables that control metastability.
2) Once it is understood which chemical parameters most heavily
influence phase stability, it becomes possible to identify the
physical changes that result in the altered kinetics. By
identifying changes that inhibit or accelerate rearrangements,
we can gain a better understanding of the actual molecular and
atomic motions that occur during a rearrangement. This both
increases fundamental understanding about transformation
mechanisms in inorganic/organic composite materials and provides
insight into the design of synthetic pathways that utilize
structural rearrangements to create new materials.
3) The authors report a study investigating control of phase
stability through control of silica chemistry in ordered
silica/surfactant composites under hydrothermal conditions. The
composites were hydrothermally treated in pH 9 through pH 11
buffers while using in situ real time x-ray diffraction to
follow a hexagonal-to-lamellar structural transition. The data
were analyzed using both isothermal and nonisothermal
(temperature-ramped) kinetics to determine activation energies.
It was found that the most mildly basic conditions utilized (pH
9), which favor silica condensation, best inhibit the phase
transition and thus produce the most kinetically stable
composites. High-pH treatment, conversely, allows for the most
facile rearrangements. Condensation occurring during composite
synthesis rather than during hydrothermal treatment has a much
smaller effect on phase stability, probably because much of the
condensation that occurs during synthesis is random and not
optimally coupled to the nanoscale architecture.
References (abridged):
1. Kresge, C. T.; Leonowitz, M. E.; Roth, W. J.; Vartuli, J. C.;
Beck, J. S. Nature 1992, 359, 710.[ChemPort] Beck, J. S.;
Vartuli, J. C.; Roth, W. J.; Leonowicz, M. E.; Kresge, C. T.;
Schmitt, K. T.; Chu, C. T.-W.; Olson, D. H.; Sheppard, E. W.;
McCullen, S. B.; Higgins, J. B.; Schlenker, J. L. J. Am. Chem.
Soc. 1992, 114, 10834.
2. Huo, Q.; Margolese, D. I.; Stucky, G. D. Chem. Mater. 1996,
8, 1147.
3. Gross, A. F.; Ruiz, E. J.; Tolbert, S. H. J. Phys. Chem. B
2000, 104, 5448.
4. Gross, A. F.; Le, V. H.; Kirsch, B. L.; Riley, A. E.;
Tolbert, S. H. Chem. Mater. 2001, 13, 3571.
5. Ryoo, R.; Jun, S. J. Phys. Chem. B 1997, 101, 317.
J. Am. Chem. Soc. 2002 124:3713
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14. SELF-ORGANIZED SYSTEMS: X-RAY MEASUREMENT OF SURFACE STRESS
DISCONTINUITIES
B. Croset et al (University of Paris, FR) discuss measurement of
surface stress in self-organized systems, the authors making the
following points:
1) Self-organized surfaces are currently intensively studied
because they are seen as promising templates for further growths
[1-5]. Two alternative long-range interactions are generally
admitted as driving forces for the mesoscopic organization of
two phases on a surface: a) electrostatic interactions due to
the difference in work function between the two phases, or b)
substrate-mediated elastic interactions due to the difference in
surface stress. On one hand, as pointed out by Vanderbilt
(1992), these two interactions lead to similar dependence of the
system energy on the geometrical configuration of the two
phases. When one of the two phases is a chemisorbed phase,
quantitative estimates do not allow one to choose between these
two driving forces. On the other hand, in spite of the
universality of the arguments given by Marchenko (1982), the
chemisorbed systems leading to observation of self-organization
are very rare [2,5]. The predicted exponential dependence of the
characteristic length of self-organization with surface stress
is a possible explanation for such a rarity. Moreover, the
surface stress associated with a chemisorbed phase is very
difficult to predict even by ab initio calculations. Direct
measurements of the stress difference at a microscopic scale for
self-organized chemisorbed surfaces are therefore important.
Since elastic interactions are mediated by the bulk, a
determination of the bulk elastic relaxations should lead to the
stress difference.
2) The authors report they have performed a grazing incidence
x-ray diffraction study of the self-organized N/Cu(001) system.
Diffraction satellites associated with self-organization are
particularly intense around Bragg conditions of the bulk
crystal. Bulk elastic relaxations due to surface stress
discontinuities at domain boundaries are responsible for this
feature. A quantitative analysis shows that these relaxations,
computed by molecular dynamics or continuum elasticity, explain
very well the entire diffraction study. A difference in surface
stress of 7 newtons per meter between uncovered and N-covered
regions of the Cu surface is shown to be the driving force for
self-organization.
References (abridged):
1. J.V. Barth, H. Brune, G. ErtI, and R.J. Behm, Phys. Rev. B
42, 9307 (1990).
2. K. Kern et al., Phys. Rev. Lett. 67, 855 (1991).
3. A. A. Baski and L. J. Whitman, Phys. Rev. Lett. 74, 956
(1995).
4. S. Rousset et al., Surf. Sci. 422, 33 (1999).
5. F.M. Leibsle, S.S. Dhesi, S.D. Barrett, and A.W. Robinson,
Surf. Sci. 317, 309 (1994).
Phys. Rev. Lett. 2002 88:156103
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15. ON ENTANGLEMENT, DECOHERENCE, AND COOPER BOXES
A.D. Armour et al (Imperial College of Science, Technology, and
Medicine London, UK) discuss Cooper boxes, the authors making
the following points:
1) A Cooper box consists of a small superconducting island
weakly linked to a superconducting reservoir [8-10]. The state
of the Cooper box is determined by the balance between its
Coulomb charging energy, and the strength of the Cooper-pair
tunneling between the island and reservoir. Using an external
gate, the Cooper box can be driven into either of two states of
definite Cooper-pair number or a linear superposition of the two
states [9]. Cooper boxes are being explored as possible
candidates for qubits in future quantum computing devices since
they act as readily controllable two-level quantum systems [10].
2) The electrostatic interaction between a conducting cantilever
and a nearby Cooper box causes a displacement in the cantilever
whose sign depends on which of the two charge states the Cooper
box is in. When the Cooper box is prepared in a superposition of
charge states, it and the cantilever become entangled and the
cantilever is driven into a superposition of spatially separated
states. If the coupling is strong enough, then the separation
between the states in the superposition can become larger than
their quantum position uncertainty, and so we can describe them
as macroscopically distinct. Again using external voltage gates,
the degree of entanglement between the cantilever and the Cooper
box after a given period of interaction (which we call the wait
time) can be imprinted on the charge state of the box. For an
isolated cantilever the entanglement between the cantilever and
the Cooper box is a periodic function of the wait time. However,
because the cantilever is driven into a superposition of
spatially separated states, it will be subject to environmental
decoherence, which eventually destroys the periodicity in the
entanglement between the cantilever and the Cooper box. Of
course the Cooper box itself is also subject to environmental
decoherence, but this should not prevent the decoherence rate of
the cantilever being determined.
3) The charge state of the Cooper box can be measured with great
sensitivity and with minimum disturbance using a radio-frequency
single electron transistor. Probing the charge state of the box
after different wait times, and averaged over many different
runs, will give information about the periodicity in the degree
of entanglement of the cantilever and the Cooper box.
Furthermore, measurement of the charge state of the Cooper box
after different wait times will also allow the decoherence time
of the cantilever due to interactions with its environment to be
inferred.
References (abridged):
8. V. Bouchiat, D. Vion, P. Joyez, D. Esteve, and M. H. Devoret,
Phys. Scr. T76, 165 (1998).
9. Y. Nakamura, Yu. A. Pashkin, and J. S. Tsai, Nature (London)
398, 786 (1999).
10. Y Makhlin, G. SchtSn, and A. Shnirman, Rev. Mod. Phys. 73,
357 (2001).
Phys. Rev. Lett. 2002 88:148301
Related Background:
TWO-LEVEL JOSEPHSON-JUNCTION SYSTEMS IN QUANTUM COMPUTING A thin
insulating barrier separating two superconducting materials at
low temperature is called a "Josephson junction", and
superconducting current can flow across the junction in the
absence of an applied voltage (direct-current Josephson effect).
When the current exceeds a critical value, the zero-resistance
character of the barrier is lost. Such a junction has a number
of interesting properties when subjected to various applied
fields. So-called "Josephson effects" were predicted
theoretically by B.D. Josephson in 1962. Josephson was 22 years
of age when he made his theoretical discovery; he received the
Nobel Prize in Physics in 1973.
... ... Y. Nakamura et al (NEC Laboratories, JP) discuss two-
level Josephson-junction systems, the authors making the
following points:
1) A two-level system is a simple model widely applied to many
problems in physics. For decades, time evolution of the quantum
state of a two-level system has been extensively studied in many
contexts: e.g., nonadiabatic transition at the level crossing,
quantum state evolution under a resonant driving field (Rabi
oscillations), and the effect of a dissipative environment
coupled to the two-level system. Moreover, recent proposals for
implementations of quantum computation, which require coherent
control of the quantum state of a two-level system, i.e., a
"qubit", have increased the interest in the dynamic behavior of
a two-level system under a driving force such as an oscillation
field or a high-speed pulse.
2) One of the candidates for physical realization of a qubit is
a small Josephson-junction circuit called a "Cooper-pair box",
which consists of a small superconducting electrode connected to
a reservoir via a Josephson junction. Because of the charging
effect of the small electrode, two charge-number states, in
which the number of Cooper pairs in the "box" electrode differs
by one, constitute an effective two-level system. Because of the
collective nature of the superconducting state, this two-level
system is basically characterized simply by "macroscopic"
parameters, the Josephson energy and the charging energy, which
can be well controlled by the geometry of the circuit designed
and fabricated by present nanotechnology. Superposition of the
two charge states has been confirmed in experiments, and
coherent manipulation of the quantum state by using a dc
gate-voltage pulse has been demonstrated, i.e., coherent
oscillations between two degenerate charge states were observed.
Phys. Rev. Lett. 2001 87:246601
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16. MOLECULAR SELF-ASSEMBLY ON METAL SUBSTRATES
S. Lukas et al (Ruhr University Bochum, DE) discuss molecular
self-assembly on metal substrates, the authors making the
following points:
1) The fabrication of nanometer-sized structures on surfaces or
interfaces is currently attracting considerable interest.
Previous work has shown that linear, one-dimensional structures
of atoms and molecules on metal surfaces can be produced by
using templates like regular arrangements of surface defects
(i.e., steps) [1-3] or special sites within a reconstruction
[4]. Since the production of templates can be a challenging task
in itself, recently the so-called supramolecular approach has
attracted more interest. In this case the formation of molecular
nanostructures proceeds by self-assembly on a flat, unstructured
substrate by employing directional intermolecular interactions
such as hydrogen bonds [5]. Not all molecules, however, are
suited for this approach since adding molecular functions
required for the intermolecular interactions (e.g..
carboxy-units), will in general change the electronic properties
of the original molecule and thus limits this approach to a
particular class of molecules. Pentacene [C(sub22)H(sub14)], an
aromatic hydrocarbon, for example, is not suited for such an
approach since this molecule cannot form hydrogen bonds.
2) On the other hand, pentacene has recently attracted a
considerable amount of attention due to its fascinating
electronic properties. In addition to pentacene single crystals
showing superconductivity for both electrons and holes, this
material has been successfully used to build high-performance
organic field effect transistors (OFETs) and related devices.
However, the deposition of ultra-thin single-crystalline films
from this material on a solid substrate has not yet been
successfully carried out. This problem is related to the fact
that on flat and rather weakly interacting metal surfaces like
Cu(111) neither benzene nor molecules with a larger number of
aromatic rings show any lateral order. Templates like regular
arrays of steps are required to obtain such 2-dimensional order.
As a result, the growth of ordered pentacene adlayers by epitaxy
on these substrates is very difficult or impossible. In
contrast, for aromatic molecules with additional functional
groups which provide a specific substrate interaction, epitaxial
structures with a high degree of order could be grown by using
heteroepitaxy on metal substrates. Finding a way to employ
self-organization for the formation of two-dimensionally ordered
adlayers of pentacene would thus not only allow for the
fabrication of nanostructures but would also open the
possibility to produce highly oriented pentacene layers by
epitaxy for use in electronic devices.
3) The authors report that the formation of one-dimensional,
unidirectional nanoscopic molecular structures by self-assembly
on metal substrates with a long range ordering up to several
hundred nanometers has been achieved by a novel mechanism, an
oscillatory modulation of the adsorption energy due to
charge-density waves related to a surface state. For the case of
pentacene adsorbed on Cu(110), annealing at 400 kelvins produces
a regular pattern of molecular wires one molecule wide (15.6
angstroms) and a wire-to-wire distance of 28 +- 2 angstroms.
Results obtained for similar compounds suggest that the
underlying mechanism is rather general and can be applied also
for other linear aromatic molecules.
References (abridged):
1. T. Jung, R. Schlittler, J. K. Gimzewski, and F. J. Himpsel,
Appl. Phys. A 61, 467 (1995).
2. V. Marsico, M. Blanc, K. Kuhnke, and K. Kern, Phys. Rev.
Lett. 78, 94 (1997).
3. M. Boehringer, K. Morgenstern, W. D. Schneider, M. Wuehn, Ch.
Woell, and R. Berndt, Surf. Sci. 444, 199 (2000).
4. M. Boehringer, K. Morgenstern, W. D. Schneider, R. Berndt, F.
Mauri, A. de Vita, and R. Car, Phys. Rev. Lett. 83, 324 (l999)
5. J. V. Barth, J. Weckesser, C. Cai, P. Guenter, L. Buergi, 0.
Jeandupeux, and K. Kern, Angew. Chem., Int. Ed. Engl. 39, 1230
(2000).
Phys. Rev. Lett. 2002 88:028301
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17. CONJUGATED POLYELECTROLYTES AS BIOSENSORS
D. Wang et al (University of California Santa Barbara, US)
discuss conjugated polyelectrolytes, the authors making the
following points:
1) Conjugated polymers are a versatile class of organic
materials that promise utility in a variety of applications
ranging from antistatic coatings, electrodes, and transistors,
to light-emitting diodes, large area displays, photodetectors,
photovoltaic cells, and lasers (1-3). The electrical, optical,
and electrochemical properties of conjugated polymers can be
modified by chemical synthesis and are strongly affected by
relatively small perturbations, including changes in
temperature, solvent, or chemical environment. As a result of
this sensitivity, conjugated polymers are promising as sensory
materials (4, 5); sensing may be accomplished by transducing
and/or amplifying physical or chemical changes into electrical,
optical, or electrochemical signals. Conjugated polymers have
been used to detect chemical species (chemosensors), such as
ions, gases (for example, trinitrotoluene), and other chemicals,
or biomolecules such as proteins, antibodies, and DNA, using
electrical, chromic, electrochemical, photoluminescent,
chemoluminescent, or gravimetric responses.
2) Contemporary biosensor and bioassay developments have focused
on mimicking natural host-receptor ("lock-and-key")
interactions. "Lock-and-key" molecular recognition can be
between enzyme and substrate, ligand and receptor, antibody and
antigen, or between two strands of nucleic acids with
complementary sequences. Although antibody-based ELISAs
(enzyme-linked immunosorbent assays) are widely used for
detection of biological species with high sensitivity, these
assays are relatively labor-intensive and time-consuming (hours
to days) and require two different antibodies of defined
specificities to adequately detect the target molecule
(potentially making them cumbersome to perform). Additionally,
the detection of small molecules using ELISA can seldom be
accomplished because of the recognition of one epitope by both
capture and detection antibodies. Therefore, competition assays
have to be performed that are both less accurate and more time
consuming.
3) Biosensors based on conjugated polymers as sensory materials
exhibit real-time response (electrochemical or optical) to the
ligand-receptor recognition event. The coupling of a recognition
event to photoinduced electron transfer or a change in the
electronic structure of the conjugated polymer produces changes
in the luminescence, UV-visible absorption, or redox potential
of the polymer (4, 5).
References (abridged):
1. Skotheim, T. A. , Reynolds, J. & Elsenbaumer, R. (1998)
Handbook of Conducting Polymers (Dekker, New York)
2. Friend, R. H , Gymer, R. W , Holmes, A. B , Burroughes, J. H
, Marks, R. N , Taliani, C , Bradley, D. D. C , Dos Santos, D. A
, Bredas, J. L , Logdlund, M. , et al. (1999) Nature (London)
397, 121-128
3. McGehee, M. D. , Miller, E. K. , Moses, D. & Heeger, A. J.
(2000) in Twenty Years of Conducting Polymers: From Fundamental
Science to Applications, ed. Bernier, P. (Elsevier, Amsterdam).
4. Leclerc, M. (1999) Adv. Mater. 11, 1491-1498
5. McQuade, D. T. , Pullen, A. E. & Swager, T. M. (2000) Chem.
Rev. 100, 2537-2574
Proc. Nat. Acad. Sci. 2002 99:49
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18. ORGANIZATION OF 2-DIMENSIONAL PHOSPHOLIPID MONOLAYERS ON A
GEL-FORMING SUBSTRATE
B. Struth et al (European Synchrotron Radiation Facility
Grenoble, FR) discuss phospholipid monolayers, the authors
making the following points:
1) Reversible sol-gel transitions are accompanied by a
divergence of viscosity and the appearance of an elastic modulus
related to the buildup of a gel network that can immobilize
large amounts of liquid. The surface properties of such gelling
structures are largely unexplored. As model systems, aqueous
clay gels [1,2], beside their fundamental interest, have also
practical applications in many industrial processes [3,4].
2) The air-water interface has proved to be ideal for the study
of associations of lipid monolayers with adsorption layers such
as proteins [5] or polyelectrolytes. Furthermore, organic
complexes with clay minerals and ternary systems made up of clay
minerals, organic compounds, and water are of interest in the
study of adsorption processes in physics, chemistry, and
biology. Such systems also have a technological importance,
since their properties play a central role in industrial
processes such as soil remediation and fabrication of cosmetic
care products, roughcasts, and paint coatings.
3) The motivation to study a phospholipid monolayer on a gel
surface goes beyond the biophysical membrane aspect of such a
monolayer and the wide technological interest of gels. The
investigation of a phospholipid-gel system raises a series of
novel issues, since it combines many fundamental aspects of
surface science with properties of complex fluids: due to
thermal fluctuations, the ordering of 2-dimensional organic
monolayers on liquid surfaces does not extend to long-range
scales, which may be a problem for applications. The aim of the
authors was to study the free and lipid covered surface of a
liquid sol undergoing a sol-gel transition. Strong effects are
expected on the monolayer structure, since the 2-dimensional
system will now be coupled to a 3-dimensional substrate of
increasing viscoelasticity. The authors report they obtained for
the first time detailed structural information on free sol and
gel surfaces and on the 2-dimensional ordering of phospholipid
monolayers deposited on these phases. Such detailed
investigations were made possible by the use of synchrotron
x-ray radiation surface scattering techniques.
4) In summary: The authors report the the gelation process is
accompanied by the formation of a single layer of mineral
particles beneath the surface, this layer inducing a
reorganization of the lipidic monolayers.
References (abridged):
1. H. van Olphen, Discuss. Faraday Soc. 11, 82-84 (1951).
2. A. Mourchid et al., Langmuir 11, 1942-1950 (1995).
3. H. K. Schmidt et al., J. Sol-Gel Sci. Technol. 13, 397-404
(1998).
4. C. J. Brinker and G. W. Scherer, Sol-Gel Science (Academic
Press, San Diego, 1990).
5. H. Haas, G. Brezesinski, and H. Mohwald, Biophys. J. 68, 312
(1995).
Phys. Rev. Lett. 2002 88:025502
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19. HIV PATIENTS IN THE US: RACIAL AND ETHNIC DISPARITIES IN
PARTICIPATION IN RESEARCH AND ACCESS TO EXPERIMENTAL TREATMENTS
A.L. Gifford et al (University of California San Diego, US)
discuss HIV treatment in the US, the authors making the
following points:
1) Clinical research should involve diverse populations of
patients.(1,2,3) Race, sex, and other sociodemographic factors
can influence the course of disease, the response to treatment,
the types of toxic effects, and health-related behavior, with
the result that the degree of diversity can affect the
generalizability of the results.(4,5) Choosing research cohorts
that resemble the target clinical population may improve the
likelihood that new therapies will be accepted by patients and
their doctors. Many patients with serious diseases have few or
no options for conventional treatment, so enrollment in trials
of experimental treatments or new applications of existing
medications can be the only means of access to needed care.
2) Human immunodeficiency virus (HIV) infection is a case in
point. The course of HIV disease is affected by the biology of
the host and socially influenced health-related behavior. Those
with HIV often have special needs and few options: their median
household income is about one third that of typical households
in the United States; they are four times as likely to be
members of an underserved minority than to be white; and
conventional therapy for HIV commonly fails.
3) Available studies suggest that minority groups and women are
underrepresented in trials of treatment for HIV infection.
However, these studies lack accuracy and detail because they
have been confined to selected sites or because they compare the
proportions of known trial participants of different races or
ethnic groups and sexes with estimates of the proportions in the
overall population. Although such comparisons are attractively
simple, they are problematic, because data from most privately
funded trials, unpublished studies, and expanded-access programs
are unavailable; because the local or national surveillance data
used for comparison may not represent all the patients for whom
investigational therapies would be appropriate; and because the
characteristics of persons who do not participate in trials are
not accounted for. To address these issues, the authors report
they used nationally representative data from the HIV Cost and
Services Utilization Study to determine the characteristics of
the participants in trials of medications for HIV and whether or
not patients with HIV had access to research trials and
experimental treatments.
The authors conclude that among patients with HIV infection,
participation in research trials and access to experimental
treatment is influenced by race or ethnic group and type of
health insurance.
References (abridged):
1. National Institutes of Health. NIH guidelines on the
inclusion of women and minorities as subjects in clinical
research. Fed Regist 1994;59:14508-14513.
2. Outreach notebook for the NIH guidelines on inclusion of
women and minorities as subjects in clinical research. Bethesda,
Md.: National Institutes of Health, 1994. (Also available at
http://www4.od.nih.gov/orwh/outreach.pdf )
3. el-Sadr W, Capps L. The challenge of minority recruitment in
clinical trials for AIDS. JAMA 1992;267:954-957.
4. Hader SL, Smith DK, Moore JS, Holmberg SD. HIV infection in
women in the United States: status at the Millennium. JAMA
2001;285:1186-1192.
5. Johnson JA. Influence of race or ethnicity on
pharmacokinetics of drugs. J Pharm Sci 1997;86:1328-1333.
New Engl. J. Med. 2002 346:1373
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20. US HOMICIDE RISK DURING INFANCY 1989-1998
The Morbidity and Mortality Weekly Report (Centers for Disease
Control and Prevention, US) discusses the risk of infant
homicide in the US, the report making the following points:
1) Homicide is the 15th leading cause of death during the first
year of life (i.e., infancy) in the United States. In addition,
the risk for homicide is greater in infancy than in any other
year of childhood before age 17 years(1) and is greatest during
the first 4 months of life.(2) To determine how the risk for
homicide varied by week during infancy and by day during the
first week of life, CDC analyzed death certificate data for
1989-1998. The report summarizes the results of this analysis,
which indicated that risk for infant homicide is greatest on the
day of birth. Efforts to prevent infant homicides should focus
on early infancy.
2) During 1989-1998, a total of 3,312 infant homicides were
reported for a rate of 8.3 per 100,000 person years. Of these,
81 (2.4%) were excluded because of a missing date of birth. The
proportion of homicides occurring each week of infancy varied,
with 9.1% of homicides occurring during the first week of life;
a secondary peak in the distribution of homicides occurred at
week 8.
3) Among homicides during the first week of life, 82.6% occurred
on the day of birth, 9.2% on the second day, and 8.2% during the
remainder of the week. After the first 2 days of life, the
number of deaths in the remainder of the first week was
comparable to the number of deaths in the second week of life.
Overall, 243 (7.3%) of all infant homicides occurred on the day
of birth. When homicide rates on the first day of life and
during the remainder of infancy were compared with homicide
rates during later age groups, the homicide rate on the first
day of life was at least ten times greater than the rate during
any other time of life.
4) The CDC comments on this report: The findings in this report
highlight the high risk for homicide on the day of birth. Risk
is comparatively small after the day of birth, even during the
highest risk periods of adulthood. Among homicides on the first
day of life, 95% of the victims are not born in a hospital.
Among homicides later in infancy, 8% of infants are not born in
a hospital.(2) Among homicides during the first week of life,
89% of known perpetrators are female, usually the mother.(4)
Mothers who kill their infants are more likely to be adolescents
and have a history of mental illness.(2,5) The secondary peak in
risk in week 8 might reflect the peak in the daily duration of
crying among normal infants between weeks 6 and 8.6.
References (abridged):
1. Murphy SL. Deaths: Final data for 1998. National vital
statistics reports; vol. 48, no. 11. Hyattsville, Maryland:
National Center for Health Statistics, 2000.
2. Overpeck MD, Brenner RA, Trumble AC, Trifiletti LB, Berendes
HW. Risk factors for infant homicide in the United States. N
Engl J Med. 1998;339:1211-6.
3. World Health Organization. Manual of the international
statistical classification of diseases, injuries, and causes of
death, based on the recommendations of the Ninth Revision
Conference, 1975. Geneva, Switzerland: World Health
Organization, 1977.
4. Jason J, Gilliland JC, Tyler CW. Homicide as a cause of
pediatric mortality in the United States. Pediatrics.
1983;72:191-7.
5. Resnick PJ. Child murder by parents: a psychiatric review of
filicide. Am J Psychiatry. 1969;126:325-334.
J. Am. Med. Assoc. 2002 287:2208 MMWR 2002 51:187
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21. ON ADVERSE DRUG REACTIONS
K.E. Lasser et al (Harvard University, US) discuss adverse drug
reactions, the authors making the following points:
1) Adverse drug reactions are believed to be a leading cause of
death in the United States.(1) Prior to approval, drugs are
studied in selected populations(2,3) for limited periods,
possibly contributing to an increased risk of adverse drug
reactions after approval. Pharmaceutical companies frequently
market new drugs heavily to both patients and clinicians before
the full range of adverse drug reactions is ascertained.
Inadequate clinician reporting may delay detection of
postmarketing adverse drug reactions; less than 10% of all
adverse drug reactions are estimated to be reported to
MEDWATCH,(4) the Food and Drug Administration's (FDA's)
voluntary postmarketing reporting system.
2) Patient exposure to new drugs with unknown toxic effects may
be extensive. Nearly 20 million patients in the United States
took at least 1 of the 5 drugs withdrawn from the market between
September 1997 and September 1998.(5) Three of these 5 drugs
were new, having been on the market for less than 2 years. Seven
drugs approved since 1993 and subsequently withdrawn from the
market have been reported as possibly contributing to 1002
deaths. For example, cisapride was approved for the treatment of
a benign condition, nocturnal gastroesophageal reflux in adults.
After its introduction, many pediatricians prescribed the drug
to infants with gastric reflux, 24 of whom were reported to have
died.
3) Few data are available on how frequently serious adverse drug
reactions are discovered after drug introduction. Previous
studies examining drug labeling changes have found high rates of
undetected postapproval risks with low rates of subsequent drug
withdrawal. However, no study has analyzed changes in the
Physicians' Desk Reference, the most commonly used source of
labeling information.
4) The authors report they analyzed the incidence of new black
box warnings in the Physicians' Desk Reference from 1975 to
2000, a marker of the most serious adverse drug reactions, and
used survival analyses to determine the course of their
discovery. They also calculated the frequency and timing of drug
withdrawals over this period.
5) The authors conclude: Serious adverse drug reactions commonly
emerge after Food and Drug Administration approval. The safety
of new agents cannot be known with certainty until a drug has
been on the market for many years.
References (abridged):
1. Lazarou J, Pomeranz B, Corey PN. Incidence of adverse drug
reactions in hospitalized patients: a meta-analysis of
prospective studies. JAMA. 1998 279:1200-1205.
2. Brewer T, Colditz G. Postmarketing surveillance and adverse
drug reactions: current perspectives and future needs. JAMA.
1999;281:824-829.
3. Thase ME. How should efficacy be evaluated in randomized
clinical trials of treatments for depression? J Clin Psychiatry.
1999 60(suppl 4):23-31.
4. Wood AJ. Thrombotic thrombocytopenic purpura and clopidogrel:
a need for new approaches to drug safety. N Engl J Med. 2000
342:1824-1826.
5. Wood AJ. The safety of new medicines: the importance of
asking the right questions. JAMA. 1999;281:1753-1754.
J. Am. Med. Assoc. 2002 287:2215
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22. FROG DEFORMITIES PRODUCED BY LOW DOSES OF A HERBICIDE
T.B. Hayes et al (University of California Berkeley, US) discuss
herbicide effects on frogs, the authors making the following
points:
1) In the last 10 years, a great deal of attention has focused
on the global presence of endocrine-disrupting contaminants in
the environment (1, 2). Similarly, a great deal of attention has
focused on global amphibian declines (3, 4). In the case of
amphibian declines, efforts focus on identifying causes (5),
whereas for endocrine disruptors, the "causes" have been
identified and studies focus on identifying effects of endocrine
disruptors in the environment.
2) Atrazine
(2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine) is the
most commonly used herbicide in the U.S. and probably the world.
The U.S. Department of Agriculture reports that more than 30,000
tons (60 million pounds) are used annually in the U.S. alone.
Atrazine has been used for over 40 years and currently it is
used in more than 80 countries. Despite its widespread intensive
use, atrazine is considered safe because of its short half-life
and negligible bioaccumulation and biomagnification. Also,
atrazine seems to have very few effects on adults and reportedly
induces abnormalities and deformities only at very high doses.
As a result of the high doses required to produce deformities,
it has been suggested that "direct toxicity of atrazine is
probably not a significant factor in recent amphibian declines".
3) The authors report a study to test the hypothesis that
atrazine may interfere with metamorphosis and sex
differentiation at ecologically relevant low doses via
endocrine-disrupting mechanisms. The authors report they
examined the effects of atrazine on sexual development in
African clawed frogs (Xenopus laevis). Larvae were exposed to
atrazine (0.01-200 ppb) by immersion throughout larval
development, and the authors examined gonadal histology and
laryngeal size at metamorphosis. Atrazine (0.1 ppb) induced
hermaphroditism and demasculinized the larynges of exposed males
(1.0 ppb). In addition, the authors examined plasma testosterone
levels in sexually mature males. Male X. laevis suffered a
10-fold decrease in testosterone levels when exposed to 25 ppb
atrazine.
4) The authors hypothesize that atrazine induces aromatase and
promotes the conversion of testosterone to estrogen. This
disruption in steroidogenesis likely explains the
demasculinization of the male larynx and the production of
hermaphrodites. The effective levels reported in the current
study are realistic exposures that suggest that other amphibian
species exposed to atrazine in the wild could be at risk of
impaired sexual development. This widespread compound and other
environmental endocrine disruptors may be a factor in global
amphibian declines.
References (abridged):
1. Sonnenschein, C. & Soto, A. M. (1998) J. Steroid Biochem.
Mol. Biol. 65, 143-150
2. Cooper, R. L. , Goldman, J. M. & Stoker, T. E. (1999)
Toxicol. Ind. Health 15, 26-36 Wake, D. B. (1991)
4. Houlahan, J. E. , Findlay, C. S. , Schmidt, B. R. , Meyer, A.
H. & Kuzmin, S. L. (2000) Nature (London) 404, 752-755
5. Kiesecker, J. M. , Blaustein, A. R. & Belden, L. K. (2001)
Nature (London) 410, 681-684
Proc. Nat. Acad. Sci. 2002 99:5476
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23. ON DECHLORINATION OF HALOGENATED ORGANICS
J. Gan et al (University of California Riverside, US) discuss
dechlorination of halogenated organics, the authors making the
following points:
1) Halogenated organic compounds (XOC, where X denotes Cl, Br,
or I) are among the most widely used man-made chemicals. A great
number of these compound -- such as the chlorinated solvents,
polychlorinated benzenes (PCBs), chloroflurocarbons (CFCs),
fumigants, and pesticides, among many others -- are also
notorious environmental contaminants. Many of these compounds
are resistant to natural degradation in the environment, and a
great effort is being made to prevent further pollution and to
restore environmental systems that are already polluted from
previous uses (1). Currently, however, there are few safe and
effective decontamination methods. Extensive research is being
conducted to explore the use of microorganisms to degrade these
compounds (1-4). Degraders are rare for many compounds, and for
those that do exist, release of microbes into unconfined
systems, e.g., aquifers that serve as water supplies, may rouse
public concerns (3). Treatments based on chemical oxidation
reactions, such as oxidation with hydrogen peroxide, potassium
permanganate, or ozone, and physical means, such as solvent
flushing and thermal treatments, are nonselective and may,
therefore, damage the environmental systems that receive the
treatment. Thus, there is a great need to initiate new and
selective approaches to decontaminate these compounds.
2) The authors report they have found that chloroacetanilide
herbicides are rapidly dechlorinated in water, sand, and soil by
thiosulfate salts under ambient conditions. Structural and
kinetics analysis suggests that the reaction occurred by
S(subN)2 nucleophilic substitution, in which the chlorine was
replaced by thiosulfate and the herbicide was detoxified.
Laboratory studies showed that this reaction could be used for
removing residues of chloroacetanilide herbicides in water,
soil, and sand. The authors suggest their findings also indicate
that some other XOCs may be subject to this reaction. Because
common thiosulfate salts are innocuous products (e.g.,
fertilizers) and the reaction selectively detoxifies XOCs at low
thiosulfate levels, the authors suggest this discovery may lead
to a new way for safe removal of certain XOCs from the
environment.
References (abridged):
1. Coates, J. , Bruce, R. & Haddock, J. (1998) Nature (London)
396, 730
2. Adrian, L. , Szewzyk, U. , Wecke, J. & Gorisch, H. (2000)
Nature (London) 408, 580-583
3. Zwillich, T. (2000) Science 289, 2266-2267
4. Lovley, D. R. (2001) Science 293, 1444-1446
5. Gan, J. , Yates, S. R. , Becker, J. O. & Wang, D. (1998)
Environ. Sci. Technol. 32, 2438-2441
Proc. Nat. Acad. Sci. 2002 99:5189
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24. DISCOVERY OF PRIONS IN MAMMALIAN SKELETAL MUSCLE
Prions are a class of poorly understood proteins implicated in a
number of exotic human neurological diseases and in some common
animal diseases such as sheep scrapie and bovine spongiform
encephalopathy in cattle ("mad cow disease"). Spongiform
encephalopathies are a type of brain disease found in humans and
animals and are characterized by macroscopic vacancies produced
by the disease process (the brain has a sponge-like appearance).
What is remarkable about prions is that they behave as
infectious agents, but they are 100 times smaller than viruses
and their mechanism of replication is unclear. One human disease
in which prions have been strongly implicated is
Creutzfeldt-Jakob disease (CJD), which appears to have a genetic
basis in about 15% of the cases. All the prion diseases are
apparently associated with the accumulation in the brain of an
abnormal protease-resistant isoform of the prion protein. In
other words, an abnormal variant of the normal prion protein is
somehow copied or produced by the disease process, which can be
initiated by introducing infectious prion into the system.
P.J. Bosque et al (University of California San Francisco, US)
discuss prions in skeletal muscle, the authors making the
following points:
1) Prions cause neurodegenerative diseases, including
Creutzfeldt-Jakob disease (CJD), bovine spongiform
encephalopathy (BSE), chronic wasting disease (CWD), and scrapie
in mammals (1). The only known constituent of the infectious
prion is an aberrant isoform (PrPSc) of the normal cellular
(PrPC) prion protein (PrP). PrPC is a cell-surface glycoprotein,
the expression of which is necessary for the production of
prions (2, 3). In animals with clinical signs of scrapie, the
highest levels of prions are found in the brain and spinal cord,
but other tissues, particularly those of the reticuloendothelial
system, exhibit substantial prion titers (4, 5).
2) It is important that animal tissues bearing high prion titers
be excluded from the human food supply. Transmission of prions
by oral ingestion of infected tissues is well documented in
rodents and more recently in cattle and sheep. The efficiency of
transmission of prion disease between species is governed by a
phenomenon commonly known as the "species barrier." This barrier
is influenced by differences in the amino acid sequence of PrP
between the species, but recent data clearly demonstrate that
the barrier to prion transmission between any two species also
depends on the particular prion strain. As yet, a reliable
procedure of experimentally or theoretically predicting the
barrier to prion transmission from prion-infected animals to
humans does not exist. Although BSE prions have been transmitted
to teenagers and young adults from infected cattle, and kuru was
transmitted among humans by ritualistic cannibalism, it remains
unclear whether cervid (deer) prions in North America have been
transmitted to humans. Animal muscle comprises a substantial
portion of the human diet, but whether prions can be found in
muscle has not been thoroughly examined using sensitive assays.
3) The authors report that prions propagate and accumulate in
skeletal muscle of mice in a region-specific manner, and at
levels much higher than have been generally assumed. The authors
suggest that their finding that some muscles are intrinsically
capable of accumulating substantial titers of prions is of
particular concern. Because significant dietary exposure to
prions might occur through the consumption of meat, even if it
is largely free of neural and lymphatic tissue, a comprehensive
effort to map the distribution of prions in the muscle of
infected livestock is needed. Furthermore, muscle may provide a
readily biopsied tissue from which to diagnose prion disease in
asymptomatic animals and even humans.
References (abridged):
1. Prusiner, S. B. (1982) Science 216, 136-144
2. Büeler, H. , Aguzzi, A. , Sailer, A. , Greiner, R.-A. ,
Autenried, P. , Aguet, M. & Weissmann, C. (1993) Cell 73,
1339-1347
3. Prusiner, S. B. , Groth, D. , Serban, A. , Koehler, R. ,
Foster, D. , Torchia, M. , Burton, D. , Yang, S.-L. & DeArmond,
S. J. (1993) Proc. Natl. Acad. Sci. USA 90, 10608-10612
4. Eklund, C. M. , Kennedy, R. C. & Hadlow, W. J. (1967) J.
Infect. Dis. 117, 15-22
5. Hadlow, W. J. , Kennedy, R. C. , Race, R. E. & Eklund, C. M.
(1980) Vet. Pathol. 17, 187-199
Proc. Nat. Acad. Sci. 2002 99:3812
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25. IN FOCUS: ON THERMODYNAMICS AND STATISTICAL PHYSICS
"The amazing feature of thermodynamics is that a few simple and
negative statements lead to such far-reaching consequences as
the existence of absolute temperature and of entropy, and to a
great number of numerical relations between measurable
quantities, such as specific heat, compressibility, thermal
expansion, galvano-and thermo-electric coefficients, chemical
affinities, etc. However, thermodynamics is, in spite of its
name, only a formal connection between thermal and dynamical
properties. The real identity of heat with motion was
established by the kinetic theory, first of the gases, later of
systems of a more general kind. You all know the fundamental
idea: it is neither possible nor necessary to know each detail
of the motion of all the innumerable atoms in a piece of matter,
but it suffices to know their average behavior in order to
predict the measurable phenomena. In this way statistics is
introduced into mechanics. The principles of statistical
mechanics have developed step by step, by trial and error, from
the first establishment of Maxwell's distribution law of
velocities to the most complex generalizations of Boltzmann,
Gibbs, Fowler and Darwin. These principles involve of course the
concept of probability and share its controversial character. As
far as I see the only foundation of the doctrine of probability,
which (though not satisfactory for a mind devoted to the
'absolute') seems at least not more mysterious than science as a
whole, is the empirical attitude: The laws of probability are
valid just as any other physical law in virtue of the agreement
of their consequences with experience. The development of
statistical physics is a demonstration of this view. Each
statistic depends on the choice of equally probable cases, or,
more generally, on the choice of the weight of a given
distribution. It is true that the invariance properties of the
equations of classical mechanics restrict this choice to some
degree (by the so-called theorem of Liouville), but the result
that the statistical weight is proportional to the extension in
phase-space (coordinates and momenta) can be justified only by
the agreement of the consequences with observations. The same
holds for the modifications introduced by quantum theory. The
description of the statistical weights is even simpler for
quantized systems: each state of given energy which by no
physical means can be split into several stages has the same
weight. This assumption has been checked by numerous examples;
if it is for instance applied to the case of electric
oscillators emitting and absorbing radiation one obtains for the
latter Planck's law."
Max Born: Experiment and Theory in Physics, Cambridge University
Press, 1943, p.26.
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