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ScienceWeek
SCIENCEWEEK
ScienceWeek - September 6, 2002 Vol. 6 Number 36
An Online Research Digest Published Weekly Since 1997
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Where is the information we have lost in data?
-- Hiroshi Inose and John R. Pierce
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Section 1
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1. Optical Interferometry and Modern Optical Astronomy
2. On Flowing Granular Media
3. On the Ionosphere
4. On Embryological Asymmetry
5. Neural Regulatory Elements and Pain
6. On Self-Representation in Nervous Systems
7. On Charge-Induced Distortion of Carbon Nanotubes
8. On Crystalline Silicon
9. On Information and Computation
10. On Ties Between Pharmaceutical and Tobacco Companies
11. On Rice Genomes
12. On Illness After International Travel
13. ScienceWeek Notices and Subscription Information
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Section 2
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1. OPTICAL INTERFEROMETRY AND MODERN OPTICAL ASTRONOMY
Swapan K. Saha (Indian Institute of Astrophysics Bangalore, IN)
discusses optical interferometry, the author making the
following points:
1) Optical interferometry provides physicists and astronomers
with an exquisite set of probes of the microcosmos and
macrocosmos. From the laboratory to the observatory over the
past few decades, there has been a surge of activity in
developing new tools for ground-based optical astronomy, of
which interferometry is one of the most powerful.
2) An optical interferometer is a device that combines two or
more light waves emitted from the same source at the same time
to produce interference fringes. The implementation of
interferometry in optical astronomy began more than a century
ago with the work of Fizeau (1868). Michelson and Pease (1921)
successfully measured the angular diameter of Alpha Orionis
(alpha Ori) using an interferometer based on two flat mirrors,
which allowed them to measure the fringe visibility in the
interference pattern formed by starlight at the detector plane.
However, progress was hindered by the severe image degradation
produced by atmospheric turbulence in the optical spectrum. The
field remained dormant until the development of intensity
interferometry by Hanbury Brown and Twiss (1958), a technique
that employs two adjacent sets of mirrors and photoelectric
correlation.
3) Turbulence and the concomitant development of thermal
convection in the atmosphere distort the phase and amplitude of
an incoming wave front of starlight. The longer the path, the
greater the degradation that the image suffers. Light reaching
the entrance pupil of an imaging system is coherent only within
patches of diameters of order r(sub0), Fried's parameter (Fried,
1966). This limited coherence causes blurring of the image,
which is modeled by a convolution with the point-spread
function. Both the sharpness of astronomical images and the
signal-to-noise (S/N) ratio (hence the faintness of the objects
that can be studied) depend on angular resolution, the latter
because noise comes from as much of the sky as is in the
resolution element. Thus reducing the beamwidth from, say, 1 to
0.5 arcsec reduces sky noise by a factor of 4. Two physical
phenomena limit the minimum resolvable angle at optical and
infrared (IR) wavelengths -- the diameter of the collecting area
and turbulence in the atmosphere. The crossover between
domination by aperture size (lambda/aperture diameter) and
domination by atmospheric turbulence ("seeing") occurs when the
aperture becomes larger than the size of a characteristic
turbulent element.
4) The image of a star obtained through a large telescope looks
"speckled" or grainy because different parts of the image are
blurred by small areas of turbulence in the Earth's atmosphere.
Labeyrie (1970) proposed speckle interferometry (SI), a process
that deciphers the diffraction-limited Fourier spectrum and
image features of stellar objects by taking a large number of
very-short-exposure images of the same field. Computer
assistance is then used to reconstruct from these many images a
single image that is free of turbulent areas -- in essence, an
image of the object as it might appear from space.(1-5)
References (abridged):
1. Akeson, R., M. Swain, and M. Colavita, 2000, in
Interferometry in Optical Astronomy, Proceedings of SPIE No.
4006, edited by P. J. Lena and A. Quirrenbach (SPIE,
Bellingham), p. 321.
2. Antoshkin, L. V, et al., 2000, in Adaptive Optical Systems
Technology, Proceedings of SPIE No. 4007, edited by P. L.
Wizinowich (SPIE, Bellingham), p. 232.
3. Armstrong, J. T., C. A. Hummel, and D. Mozurkewich, 1992, in
High-Resolution Imaging by Interferometry II, ESO Conference and
Workshop Proceedings No. 39, edited by J. M. Beckers and F.
Merkle (ESO, Garching, Germany), p. 673.
4. Bates, R., and M. McDonnell, 1986, Image Restoration and
Reconstruction (Clarendon, Oxford)
5. Beichman, C., 1998, in Astronomical Interferometry,
Proceedings of SPIE No. 3350, edited by R. D. Reasenberg (SPIE,
Bellingham), p. 719.
Rev. Mod. Phys. 2002 74:551
Web Links: optical interferometry optical astronomy
Related Background:
A NEW CALIBRATION OF CEPHEID-BASED DISTANCES
One of the primary challenges of astronomy is to determine with
some exactitude the distances to various astronomical objects
outside our Galaxy. Given the enormous distances involved, the
difficulties are formidable. But such data are of tremendous
importance in constraining various models of the Universe, and
are thus at the heart of the quest to understand where we are.
Variable stars are stars whose apparent physical parameters
vary, usually periodically, with the cause of the variation
either intrinsic (produced by the internal physics of the star)
or extrinsic (produced by the proximity of another star).
The Hubble constant is a measure of the rate of expansion of
the Universe, the average value of velocity of recession divided
by distance. Since the constant is time-dependent, it is more
correctly termed a parameter. It's present value is believed to
be between 50 and 100 km/sec/megaparsec.
"Cepheids" are supergiant stars that regularly change in size
and brightness, their intrinsic variation having periods between
1 and 60 days. The period of variation for each star has been
found to be related to its luminosity, and this relation makes
it possible to use Cepheids as "standard candles" to estimate
the distance of astronomical objects (*Note #1).
B.F. Lane et al (5 authors at California Institute of
Technology, US) present a new and independent calibration of the
period-luminosity relation of a Galactic Cepheid star
(zeta-Geminorum), the authors making the following points:
1) The authors point out that Cepheids are a class of variable
(pulsating) stars whose absolute luminosities are related in a
simple manner to their pulsational periods. By measuring the
period and using the "period-luminosity" relationship,
astronomers can use the observed visual brightness to determine
the distance to the star. Because these stars are very luminous,
they can be observed in other galaxies, and therefore can be
used to help determine the expansion rate of the Universe (the
Hubble constant). Calibration of the period-luminosity relation
is a necessary first step, but the small number of sufficiently
nearby Cepheids has forced the use of indirect techniques, with
associated systematic uncertainties.
2) The authors report a determination of the distance to the
Cepheid star zeta-Geminorum, the determination made using a
direct measurement (by an *optical interferometer: the Palomar
Testbed Interferometer) of its changes in diameter as it pulses.
The authors report that within their uncertainty of 15 percent,
their distance is in agreement with previous indirect
determinations. The authors suggest that planned improvements in
the instrument will allow them to calibrate directly the
period-luminosity relation to better than a few percent.
In a commentary on the above work, Tyler Nordgren (US Naval
Observatory Flagstaff, US) states: "Lane et al report the first
unambiguous detection of the pulsating diameter of a Cepheid
variable star... In their observations of zeta-Gem[inorum],
[these researchers] have done an excellent job of comparing
their observations to a wide range of previous Cepheid
observations. With new-found confidence in these difficult
observations, optical interferometry is now ready to move beyond
merely confirming previous discoveries to making new ones of its
own."
Nature 2000 407:462,485
Text Notes:
... ... *Note #1: In general, the periodic pulsations of Cepheid
variable stars involve expansion and contraction with as much as
a 30% change in size in each cycle, and a typical average
luminosity approximately 10,000 times that of our Sun. In 1912,
Henrietta Swan Leavitt discovered a simple relationship between
the period of light variation and the absolute magnitude of a
Cepheid variable. This relationship, called the
"period-luminosity law", enabled the calculation of distances to
the stars in our own Galaxy and to the stars in other galaxies.
In 1952 it was discovered that there are two types of Cepheid
variables, which meant an error had been introduced in the
earlier calculations of distances, and when the correction was
made, the apparent size of the universe abruptly doubled. During
1908-1912, Leavitt (1868-1928), a graduate of Radcliffe College
on the staff of the Harvard Observatory, discovered 2400
variable stars, doubling the number known in her time. In the
early years of stellar spectroscopy, particularly at the Harvard
Astronomical Observatory, nearly all the data was catalogued and
analyzed by female astronomers, called "computers", who were
trained professional astronomers but forbidden because of their
sex to use the telescopes. It is an irony of the social history
of science that the work of such female astronomers as Henrietta
Swan Leavitt and Annie Jump Cannon (1863-1941) came to be of
greater significance than the work of many of the male
astronomers who considered these female astronomers to be no
more than menial assistants.
... ... *optical interferometer: An interferometer combines the
light from two or more widely spaced mirrors, resulting in an
array with the same resolution as a single large telescope of
the same diameter as the separation between the mirrors. Radio
astronomers using the Very Long Baseline Array are thus able
simulate a single radio telescope the size of North America.
Unfortunately, most stars emit radiation at optical rather than
radio wavelengths, and technical obstacles have prevented
optical telescopes being built on this scale. The Palomar
Testbed Interferometer (PTI), located on Palomar Mountain in
California (US), has the resolving capability of a single
110-meter infrared telescope, much larger than any single
telescope built so far, and good enough to resolve stars as
small as a few milliarcseconds in diameter. Such interferometers
are now operating or under construction in Britain, continental
Europe, Australia, Hawaii, and North and South America.
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2. ON FLOWING GRANULAR MEDIA
E. Longhi and N. Easwar (University of Massachusetts, US)
discuss flowing granular media, the authors making the following
points:
1) Sand, rather than a liquid, is chosen for the contents of an
hourglass because the rate of efflux from a column of sand
flowing under gravity does not depend on the height to which it
is filled. Likewise, in a static column of sand, the pressure at
a given depth is independent of the height of the column above
it [1]. In both cases, this is because the weight of the sand in
the interior of the column is borne by the lateral containing
walls. In the case of a static granular column, experiments
[2-4], theory [5], and numerical simulations [3] have all shown
that there are large spatial fluctuations in the transmission of
stresses from the bulk to the walls. This is demonstrated by two
independent observations: First, the distribution of forces,
P{f), at the boundaries of the medium is exponential, rather
than Gaussian. Second, grains that are highly stressed are
organized into filamentary, linear structures called "force
chains" that carry a large fraction of the stress [2-4].
2) The authors report experiments directed toward producing a
complementary understanding of a flowing granular medium. The
force chains in a static medium are unstable to perturbations
perpendicular to their length; when jostled by other grains
moving in a flow, do they merely become short-lived, or do they
melt away entirely? Concomitant to this presumed annealing away
of the stress inhomogeneities, does the broad, exponential force
distribution in the static case become Gaussian when grains move
and rearrange? The answers to these questions have broad
consequences for the prospects of applying continuum theories to
granular flows. If, indeed, the bounding walls of a medium can
communicate with the interior by transient force chains, then
any approach to a continuum limit must take into account these
long length scales. Previous analyses of force distributions in
a static granular medium [5] show that an exponential at large
forces may be obtained from scalar models in which the weight of
a bead is borne by the beads beneath it in some random
proportion.
3) While force chains do not naturally emerge from these models,
it is tempting to speculate that force chains and broad force
distributions are related manifestations of the large stress
inhomogeneities in a granular medium. This point of view is also
suggested by recent simulations that show a simultaneous
narrowing of force distributions and a blurring of the force
chains [8], as static granular media are subjected to
compression. On the other hand, a recent proposal [11] for a
unified description of jamming in thermal as well as nonthermal
systems identifies signatures of the approach to a jammed state
in the force distribution, P(f). In contrast to earlier models,
they suggest that loss of mobility is due to the formation of
force chains, whose presence is signaled by the scarcity of
unstressed regions [i.e., a dip or plateau in P(f) at f less
than the average force] rather than by the exponential tails at
large force values. The formation of a plateau in P(f) has also
been reported in a recent simulation of grains flowing down an
inclined chute.
4) In summary: The authors report a study of fluctuations in the
force at the boundary of a 2-dimensional granular flow. The
forces are mainly impulsive at all flow rates. The probability
distribution of impulses decays exponentially at large impulses,
as do the forces in a static granular medium. At small impulses,
the distribution evolves continuously with flow rate with no
indication of the transition from collisional flow to
intermittently jamming flows. However, the distribution of the
time interval between collisions tends to a power law, showing a
clear dynamical signature of the approach to jamming.
References (abridged):
1. H.M. Jaeger, S.R. Nagel, and R.P. Behringer, Rev. Mod. Phys.
68, 1259 (1996)
2. P. Dantu, Ann. Ponts Chaussees IV, 144 (1967); T. Travers et
al., Europhys. Lett. 4, 329 (1987)
3. C.H. Liu et al., Science 269, 513 (1995)
4. D. Howell, R. P. Behringer, and C. Veje, Phys. Rev. Lett. 82,
5241 (1999)
5. S. N. Coppersmith et al., Phys. Rev. E 53, 4673 (1996)
Phys. Rev. Lett. 2002 89:045501
Web Links: flowing granular media
Related Background:
JAMMING AND THE GLASS STATE
G. D'Anna and G. Grimaud (Ecole Polytechnique Lausanne, CH)
discuss jamming and make the following points:
1) It has been suggested that a common conceptual framework
known as "jamming" may be used to classify a wide variety of
physical systems that include granular media, colloidal
suspensions, and glass-forming liquids, all of which display a
critical slowdown in their dynamics before a sudden transition
to an amorphous rigid state. Decreasing the relevant control
parameter (such as temperature, drive, or inverse density) may
cause geometrical constraints to build up progressively and thus
restrict the accessible part of the system's phase space.
2) In glass-forming liquids (thermal molecular systems), jamming
is provided by the classical vitrification process of
supercooling, characterized by a rapidly increasing and
apparently diverging viscosity at sufficiently low temperatures.
In driven (athermal) macroscopic systems, a similar slowdown has
been predicted to occur, notably in sheared foam or vibrated
granular media.
3) The authors report experimental evidence for dynamic
behavior, qualitatively analogous to supercooling, in a driven
granular system of macroscopic millimeter-size particles. The
granular medium is perturbed by isolated tapping or continuous
vibration, with the perturbation intensity serving as a control
parameter. The authors observe the random deflection of an
immersed torsion oscillator that moves each time the grains
rearrange, analogous to a "thermometer" sensing the granular
noise.
4) The authors caution that their granular analogy to
supercooling is based on similarities in the dynamical behavior
rather than on quantitative theory.
Nature 2001 413:407
Related Background:
SHOCKS IN GRANULAR SYSTEMS
E.C. Rericha et al (University of Texas Austin, US) discuss
shocks in granular systems, the authors making the following
points:
1) Shocks form around an object such as a bullet or an aircraft
when the speed of the object relative to the incident flow
exceeds the speed of sound in the fluid. Shocks analogous to
those that form in fluid flows also occur in flows of
macroscopic particles such as sand grains. The usual theoretical
approach to understanding granular flows is dense-gas kinetic
theory, treating the constituent grains as colliding and
inelastic hard spheres. As in standard dense-gas kinetic theory,
flows of particles that are described by Newton's laws are
modeled with a Boltzmann equation, which in turn leads to
Navier-Stokes-like continuum equations. For granular media,
these continuum equations contain a term that describes the
overall energy loss due to inelastic collisions.
2) The inelastic collisions in a granular flow reduce the
relative velocities of the grains. Consequently, the local
granular temperature, defined as the variance of the local
velocity distribution, decreases. Whether the fluid is composed
of grains or molecules, the speed of sound depends on the speed
of the component particles and therefore on the temperature.
(For a granular fluid, the speed of sound in the interstitial
air is irrelevant: a granular fluid has the same sound speed
even if the interstices are a vacuum.) Since inelastic
conditions dissipate temperature, the speed of sound in a
granular flow decreases. In the absence of further heating, a
granular flow becomes supersonic as it progresses, i.e., the
mean particle velocity surpasses the speed of sound. Thus,
shocks form in granular systems for common rather than for
extreme conditions whenever the flow encounters an obstacle.
Phys. Rev. Lett.. 2002 88:014302
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3. ON THE IONOSPHERE
Henry Rishbeth (University of Southampton, UK) discusses the
ionosphere, the author making the following points:
1) We have come far in the 100 years since Oliver Lodge
(1851-1940) gave the first physical explanation of why M.
Marconi (1874-1937) could send radio waves around the curved
Earth. Using the new knowledge of electrons and ionization,
Lodge realized that solar ultraviolet radiation produces a
conducting layer that reflects radio waves. We call this the
"ionosphere", a term coined by Robert Watson-Watt (1892-1973) in
1926 to replace its previous name, the "Heaviside layer" (after
the physicist Oliver Heaviside [1850-1925]). In modern terms,
the ionosphere is a weakly ionized plasma or electron-ion gas
embedded in the thermosphere, the hot, tenuous region above 80
km that comprises the top few millionths of the atmosphere's
mass. We are now approaching the stage where we can link our
models of the thermosphere and ionosphere with models of the
lower atmosphere.
2) For a century the ionosphere has been used for
communications, but it is by no means a constant "mirror in the
sky". Although its E layer (100-120 km above the ground) and F1
layer (170-200 km) usually behave in a regular, solar-controlled
way, the F2 layer (250-350 km) does not. It is this F2 layer,
with the greatest density of free electrons, that is potentially
the most effective reflector of radio waves. But its variability
in height and density, its strange day/night and seasonal
behavior, and its complex response to geomagnetic disturbances
have long puzzled scientists and infuriated users of radio
communications. This matters because the ionosphere is still
widely used for radio communication; furthermore, the ionosphere
can severely affect satellite transmissions that pass through
it, causing errors in the Global Positioning System, for
example. Ionospheric disturbances can also create strong
electric currents in the E layer that can disrupt cable
communications and terrestrial electric power systems.
3) Rockets, satellites and radar have enabled us to build up a
comprehensive picture of the upper atmosphere. The ionospheric
plasma -- being far easier to detect and measure than the
neutral atoms and molecules -- serves as a "tracer", the
ionospheric measurements acting as "diagnostics" for the
composition, temperature and dynamics of the greatly
preponderant neutral air. Like the lower atmosphere, the
thermosphere is a heat engine on a global scale, driven by
radiation from the Sun. Whereas the lower atmospheric engine is
driven by infrared and visible radiation, the thermosphere is
driven by short-wavelength ultraviolet and X-radiation which
heats, dissociates, and ionizes the air. It is also driven by
the energy input from the particle stream known as the "solar
wind", which shapes and controls the Earth's magnetic envelope
-- the magnetosphere -- and deposits heat in the auroral zones
that surround the Earth's magnetic poles.(1-4)
References:
1. Lodge, O. Nature 66, 222 (1902)
2. Hargreaves, J. K. The Solar-Terrestrial Environment
(Cambridge Univ. Press, 1992)
3. Roble, R. G. Am. Geophys. Un. Monogr. 123, 53 (2000)
4. Schunk, R. W. & Nagy, A. E. Ionospheres: Physics, Plasma
Physics and Chemistry (Cambridge Univ. Press, 2000). Gardner, G.
W. Nature 224, 1096 (1969).
http://www.wdc.rl.ac.uk/ionosondes/ionosondes.html
Nature 2002 418:23
Web Links: ionosphere thermosphere
Related Background Brief:
MICROBIOLOGICAL STUDIES ON THE RADIATION ENVIRONMENT OF THE
IONOSPHERE AND STRATOSPHERE. The authors report that rocket,
balloon and laboratory experiments have been performed in order
to study the survival chances of microorganisms, which exist
under the environmental conditions of ionosphere and
stratosphere. The main results are: 1. Not only near the Earth,
but also in the stratosphere and even in the ionosphere,
microorganisms are endangered primarily by UV- and EUV-light
irradiation. 2. The observed effect of more penetrating kinds of
radiation was relatively unimportant. High-vacuum and
temperature effects have not been observed at all. Even membrane
filters and thin protein layers protected the exposed spores of
Bacillus subtilis var. niger (= Bac. globigii) in a clear-cut
manner. 3. UV-light with a wavelength between 200 and 300 nm
reduces the number of cells able to divide much quicker, than
EUV-light of the same energy level does, but damages caused by
EUV-light can not be reversed by photoreactivation. 4. Microbes
which have been damaged by solar radiation, can be
photoreactivated to a degree. Photoreactivation is high after
exposure near the Earth and significant after exposure within
the stratosphere. 5. After exposure to ionospheric irradiations
no changes in the antigenic behavior of E. coli cells could be
detected. E. Petras and K. Bisa: Life Sci Space Res 1968;6:115.
Related Background:
ON THE DISCOVERY OF THE STRATOSPHERE
The atmosphere of Earth is divisible into several layers, each
layer having a characteristic temperature range, pressure range,
and composition. The layers, from the surface of Earth, are
(with thicknesses varying at different latitudes): troposphere
(0 to approximately 10 kilometers), stratosphere (from
approximately 10 to 50 kilometers), mesosphere (approximately 50
to 80 kilometers), thermosphere (approximately 80 to 500
kilometers), and exosphere (above approximately 500 kilometers.
Other layers, essentially meta-layers, are also recognized: a)
the "chemosphere" is the region between approximately 32 and 92
kilometers where many important chemical reactions occur; b) the
"ionosphere", above approximately 80 kilometers, is a shell of
high electron concentration resulting from very short wavelength
sunlight stripping electrons from atoms and molecules (mainly
oxygen and nitrogen) to create an ionized layer; c) the
magnetosphere is the constantly changing magnetic field
generated by the Earth's dynamo, this magnetic field influencing
the behavior of electrically charged particles, and the field
extending approximately 10 Earth radii (64,000) kilometers into
space on the sunward side.
The boundary between troposphere and stratosphere is called the
"tropopause"; that between stratosphere and mesosphere is called
the "stratopause"; and that between mesosphere and thermosphere
is called the "mesopause", in each case the root "pause" used
because of an inflection in the temperature-altitude curve.
The temperature of the atmosphere undergoes marked but
systematic variation with altitude. In the troposphere, the
layer closest to the surface, the temperature decreases by
approximately 6.5 degrees centigrade per kilometer of altitude,
until at the tropopause (10 to 11 kilometers) the temperature
stabilizes at approximately -53 degrees centigrade. The
temperature remains stable in the stratosphere, and even
increases with altitude to approximately 0 degrees centigrade at
the stratopause. Then in the mesosphere there occurs again a
decline in temperature with altitude, now down to -100 degrees
centigrade, and then after the mesopause and into the upper
atmosphere (thermosphere and exosphere), the temperature rises
markedly in these regions of extremely low air density, so that
at 200 kilometers the temperature range is 300 to 900 degrees
centigrade, depending on solar radiance.
The first hint that Earth's atmosphere is a series of concentric
shells was provided by the meteorologist Leon Teisserenc de Bort
(1855-1913) [the surname is Teisserenc de Bort]. From 1892 to
1896, Teisserenc de Bort served as chief meteorologist at the
Central Meteorological Bureau in Paris, but in 1896 he resigned
and carried out his meteorological balloon investigations
himself at his estate near Versailles. He conducted experiments
with high-flying instrumented balloons, and he was one of the
pioneers in the use of such devices. He discovered that above
approximately 11 kilometers the temperature, which drops
steadily from sea-level to that altitude, remained constant up
to the highest points he could reach. Surprised by this result,
he accumulated data from 236 balloon ascents before he
suggested, in 1902, that the atmosphere was divided into 2
layers. During the next few years, he termed the lower layer,
the layer involving air movements, the "troposphere" ("sphere of
change"), and the layer above that, a layer he mistakenly
thought consisted of internal further layers, the "stratosphere"
("sphere of layers"). Thus, to Teisserenc de Bort we owe both
the discovery and the name of the stratosphere.
Mott T. Greene (University of Puget Sound Tacoma, US) presents
an essay on Teisserenc de Bort, the author making the following
points:
1) The author suggests that ripples from Teisserenc de Bort's
discovery of the stratosphere spread far beyond meteorology.
Between 1902 and 1904, the oceanographer Vagn Ekman (1874-1954)
discovered similar layering of the ocean, and in 1909, the
meteorologist Andrija Mohorovicic (1857-1936) used seismology to
establish the existence of a similar discontinuity in the solid
Earth, the discontinuity now known as the "Moho".
2) The author (Greene) also suggests that the discovery that the
Earth-ocean-atmosphere system is composed of concentric shells
of different density, from the core of the Earth to the top of
the atmosphere, is the founding insight of modern geophysics,
and that the discovery also profoundly influenced the thinking
of the young meteorologist Alfred Wegener (1880-1930), leading
Wegener in 1912 to propose the theory of continental drift, with
the continents representing the remains of a formerly continuous
Earth shell above the ocean floors. Greene concludes: "Just as
air masses and ocean water masses moved under the influence of
the Earth's rotation, sliding along surfaces of discontinuity,
so, he [Wegener] reasoned, did the continents on a longer
time-scale -- making Teisserenc de Bort not only the discoverer
of the stratosphere but an honorary grandfather of continental
drift."
Nature 2000 407:947
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4. ON EMBRYOLOGICAL ASYMMETRY
Claudio D. Stern (University College London, UK) discusses
embryological asymmetry, the author making the following points:
1) How an embryo first distinguishes its left from its right
side has baffled embryologists for a long time. The rotational
beating of cilia -- hair-like structures attached to individual
cells -- is known to be essential for the process. But cilia
have been seen only in mouse embryos, and it has remained
unclear whether their movement could really generate the
necessary molecular asymmetries.
2) Despite its superficial appearance of bilateral symmetry, the
vertebrate body plan is asymmetric in several respects, most
obviously in the position of internal organs such as the heart
and parts of the gut. Left–right asymmetry first arises in the
embryo at around the stage -- the gastrula -- when the three
major cell layers of ectoderm, mesoderm and endoderm are first
laid down. But until recently we knew virtually nothing about
the molecular mechanisms responsible(1.2).
3) The turning point came in 1995 when four genes (Sonic
hedgehog, Nodal, HNF3 and the Activin-receptor IIA) were
identified as being expressed on one or the other side of the
chick embryo at the gastrula stage, and their activities were
implicated in heart turning(3). However, subsequent work
revealed that only one of these, Nodal, is expressed
asymmetrically in all vertebrates. Shortly afterwards it was
discovered that a mouse mutant, called (iv) and characterized by
random positioning of internal organs, carries a mutation that
inactivates left–right dynein (LRD), a protein required for the
beating of cilia(4). Researchers then looked for cilia in the
mouse gastrula and found that the "node", a critical organizing
structure in the midline of the early embryo, does indeed
possess short cilia protruding from its cells, which beat in an
anticlockwise circular motion and generate a leftwards flow of
fluid that is strong enough to displace solid particles to the
left(5). But again, the cilia could be found only in the mouse.
Could different vertebrates have evolved different ways of
establishing asymmetry? And could the beating of cilia really be
sufficient to generate molecular asymmetry by removing a
"morphogen" signal from one side of the embryo and enriching it
on the other?
4) The papers by Essner et al(1) and Nonaka et al(2) answer both
questions. Essner et al. reveal that cilia, as well as LRD, are
indeed present in all the major vertebrate groups at appropriate
stages and locations to generate left–right asymmetry. Nonaka et
al. show that a flow of fluid in the reverse direction to that
generated by cilia can randomize embryonic asymmetry — and that
artificially induced fluid flow is enough to control the
position of the internal organs in (iv) mutant mice.
References (abridged):
1. Essner, J. J. et al. Nature 418, 37-38 (2002)
2. Nonaka, S., Shiratori, H., Saijoh, Y. & Hamada, H. Nature
418, 96-99 (2002)
3. Levin, M., Johnson, R. L., Stern, C. D., Kuehn, M. & Tabin,
C. Cell 82, 803-814 (1995)
4. Supp, D. M., Witte, D. P., Potter, S. S. & Brueckner, M.
Nature 389, 963-966 (1997)
5. Nonaka, S. et al. Cell 95, 829-837 (1998)
Nature 2002 418:29
Web Links: embryo asymmetry
Related Background Brief:
LEFT–RIGHT DEVELOPMENT: CONSERVED FUNCTION FOR EMBRYONIC NODAL
CILIA. How left–right handedness originates in the body plan of
the developing vertebrate embryo is a subject of considerable
debate1. In mice, a left–right bias is thought to arise from a
directional extracellular flow (nodal flow) that is generated by
dynein-dependent rotation of monocilia on the ventral surface of
the embryonic node. The authors report that the existence of
node monocilia and the expression of a dynein gene that is
implicated in ciliary function are conserved across a wide range
of vertebrate classes, indicating that a similar ciliary
mechanism may underlie the establishment of handedness in all
vertebrates. In mice, mutations in the gene that encodes the
left–right dynein heavy chain (Lrd), a component of the ciliary
motor, result in immotile node cilia and a reversal of the
left–right (L–R) axis in roughly half of mutant offspring. In
humans, mutations in the dynein heavy-chain gene DNAH5 are also
associated with immotile cilia syndrome, an inherited disorder
that includes mirror-image reversal of the internal organs in
half of affected individuals. Both Lrd and Dnahc5 are expressed
in the ventral layer of the mouse node in cells containing
cilia. J.J. Essner et al: Nature 2002 418:37
Related Background Brief:
DETERMINATION OF LEFT–RIGHT PATTERNING OF THE MOUSE EMBRYO BY
ARTIFICIAL NODAL FLOW. Substantial insight has recently been
achieved into the mechanisms responsible for the generation of
left–right (L–R) asymmetry in the vertebrate body plan. However,
the mechanism that underlies the initial breaking of symmetry
has remained unclear. In the mouse, a leftward fluid flow on the
ventral side of the node caused by the vortical motion of cilia
(referred to as nodal flow) is implicated in symmetry breaking,
but direct evidence for the role of this flow has been lacking.
The authors describe the development of a system in which mouse
embryos are cultured under an artificial fluid flow and with
which they have examined how flow affects L–R patterning. An
artificial rightward flow that was sufficiently rapid to reverse
the intrinsic leftward nodal flow resulted in reversal of situs
in wild-type embryos. The artificial flow was also able to
direct the situs of mutant mouse embryos with immotile cilia.
These results provide the first direct evidence for the role of
mechanical fluid flow in L–R patterning. S. Nonaka et al: Nature
2002 418:96.
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5. NEURAL REGULATORY ELEMENTS AND PAIN
Brent A. Vogt (State University of New York Syracuse, US)
discusses pain, the author making the following points:
1) Although some mechanisms by which acute pain evolves into a
chronic syndrome are known, many others, including changes in
the brain stem, thalamus, and cerebral cortex, are not
understood. Moreover, even though chronic neuropathic and
inflammatory pain can be relieved to some extent with opiate
compounds, these syndromes are still poorly understood. The
treatment options for pain with a central cause are even more
bleak. Currently, however, the revolution in genomic engineering
has opened up new possibilities for studying the mechanisms of
acute and chronic pain and designing novel and more selective
drugs.
2) Prodynorphin is the precursor of dynorphin, an opioid
neuropeptide. Expression of the prodynorphin gene is controlled
by a calcium-regulated transcription factor that binds to a
downstream regulatory element (DRE) of the gene and is termed
"DRE antagonistic modulator" (DREAM). When DREAM binds to DRE,
it inhibits transcription of the prodynorphin gene (1). In view
of the role of dynorphin in spinal and supraspinal modulation of
afferent nociceptive signals and its likely involvement in
chronic-pain syndromes, the DREAM transcriptional regulator
should be an important target for assessing nociceptive
transmission.
3) Opioids interact with receptors at all levels of nociceptive
and pain processing. The principal opioid receptors are the mu,
kappa, and delta subtypes. The effectiveness of compounds such
as morphine, which are selective for mu-opioid receptors,
reflects the wide distribution of mu-opioid receptors and the
ability of such compounds to block the transmission of the
nociceptor to the spinal cord and to control the perception of
pain in the cerebral cortex. Dynorphin is released by
interneurons in the spinal cord, binds to kappa-opioid receptors
on spinal-projection neurons, and has analgesic effects. It
appears, however, that dynorphin is not expressed by
nociceptors, is elevated in chronic-pain syndromes, and through
its actions at N-methyl-D-aspartate (NMDA) receptors,(3) may
actually enhance nociceptive transmission, under some
circumstances, rather than reduce it. For these reasons, the
expression of dynorphins must be under the tight control of
DREAM.(2,4,5)
References (abridged):
1. Carrion AM, Link WA, Ledo F, Mellstrom B, Naranjo JR. DREAM
is a CA2+-regulated transcriptional repressor. Nature
1999;398:80-84
2. Cheng H-YM, Pitcher GM, Laviolette SR, et al. DREAM is a
critical transcriptional repressor for pain modulation. Cell
2002;108:31-43
3. Laughlin TM, Larson AA, Wilcox GL. Mechanisms of induction of
persistent nociception by dynorphin. J Pharmacol Exp Ther
2001;299:6-11
4. Ledo F, Carrion AM, Link WA, Mellstrom B, Naranjo JR.
DREAM-CREM interaction via leucine-charged domains depresses
downstream regulatory element-dependent transcription. Mol Cell
Biol 2000;20:9120-9126
5. Jasmin L, Tien D, Weinshenker D. et al. The NK1 receptor
mediates both the hyperalgesia and the resistance to morphine in
mice lacking noradrenaline. Proc Natl Acad Sci U S A
2002;99:1029-1034
New Engl. J. Med. 2002 347:362
Web Links: physiology of pain pain receptors
Related Background:
ON NORADRENALIN, HYPERALGESIA, AND MORPHINE
L. Jasmin et al (University of California San Francisco, US)
discuss hyperalgesia, the authors making the following points:
1) Noradrenaline (NA), a key neurotransmitter of the endogenous
pain inhibitory system, acutely inhibits nociceptive
transmission (including that mediated by substance P),
potentiates opioid analgesia, and underlies part of the
antinociceptive effects of the widely prescribed tricyclic
antidepressants. Lesions of noradrenergic neurons, however,
result in either normal or reduced pain behavior and variable
changes in morphine antinociception, undermining the proposed
association between noradrenaline (NA) deficiency and chronic
pain (hyperalgesia).
2) The authors report they used mice lacking the gene coding for
dopamine beta-hydroxylase, the enzyme responsible for synthesis
of NA from dopamine, to reexamine the consequences of a lack of
NA on pain behavior. The authors report that absence of NA in
the central nervous system results in a substance P-mediated
chronic hyperalgesia (decreased nociceptive threshold) to
thermal, but not mechanical, stimuli and decreased efficacy of
morphine. Contrary to studies that show substance P-mediated
hyperalgesia requires intense stimuli, the authors found that
even a mild stimulus is sufficient to evoke substance
P-dependent hyperalgesia in the NA-deficient mice. Restoring
central NA normalized both the nociceptive threshold and
morphine efficacy, which is consistent with a tonic inhibitory
effect of NA on nociceptive transmission. Unexpectedly, however,
antagonists to the substance P receptor (the NK1 receptor) could
achieve the same effect as NA replacement. The authors conclude
that when unopposed by NA, substance P acting at the NK1
receptor causes chronic thermal hyperalgesia, and that the
reduced opioid efficacy associated with a lack of NA is due to
increased NK1-receptor stimulation.(1-5)
References (abridged):
1. Jones, S. L. (1991) Prog. Brain Res. 88, 381-394
2. Sagen, J. & Proudfit, H. K. (1984) Brain Res. 310, 295-301
3. Bourgoin, S. , Pohl, M. , Mauborgne, A. , Benoliel, J. J. ,
Collin, E. , Hamon, M. & Cesselin, F. (1993) Neuropharmacology
32, 633-640
4. Kuraishi, Y. , Hirota, N. , Sato, Y. , Kaneko, S. , Satoh, M.
& Takagi, H. (1985) Brain Res. 359, 177-182
5. Izenwasser, S. & Kornetsky, C. (1988) Pain 33, 363-368
Proc. Nat. Acad. Sci. 2002 99:1029
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6. ON SELF-REPRESENTATION IN NERVOUS SYSTEMS
Patricia S. Churchland (University of California San Diego, US)
discusses brain and self, the author making the following points:
1) What is "the self"? Descartes proposed that the self is not
identical with one's body, or indeed, with any physical thing.
Instead, he famously concluded that the essential self -- the
self one means when one thinks, "I exist" -- is a nonphysical,
conscious thing. At this stage of scientific development, the
Cartesian approach is unsatisfactory for three reasons: (a)
psychological functions generally, including conscious thoughts
such as "I exist," are activities of the physical brain (1,2);
(b) aspects of self-regulation (e.g., inhibiting sexual
inclinations), and self-cognition (e.g., knowing where I stand
in my clan's dominance hierarchy), may be nonconscious (3); and
(c) as the Scottish philosopher David Hume (1711-1776) realized,
there is in any case no introspective experience of the "self"
as a distinct thing apart from the body (4). Introspection, Hume
concluded, reveals only a continuously changing flux of visual
perceptions, sounds, smells, emotions, memories, thoughts,
feelings of fatigue, and so forth.
2) To identify the phenomenon that we want explained, it is
useful to start with the idea that one's self-concept is a set
of organizational tools for "coherencing" the brain's plans,
decisions, and perceptions. Thus, if a brick falls on my foot, I
know the pain is mine. I know without pausing to figure it out
that "this body is my own," and that a decision to fight rather
than flee is a decision affecting my body's painful encounter
with the body of another. If I scold myself about jaywalking, I
know that it is me talking to myself. We know that if we fail to
plan for future contingencies, our future selves may suffer, and
we care now about that future self. Sometimes we use "myself" to
mean "my body", as when we say "I weighed myself". By contrast,
when we say "I deceived myself", we are not referring to our
physical bodies. We talk of our social and our private selves,
of discovering and realizing ourselves, of self-control,
self-improvement, and self-denial (5).
3) This remarkably diverse range of uses of the self-concept
motivates recasting problems about "the self" in terms of
self-representational capacities of the brain. Doing so deflates
the temptation to think of the self as a singular entity and
encourages the idea that self-representing involves a plurality
of functions, each having a range of shades, levels, and
degrees. Further, it broadens the inquiry beyond humans to other
species, suggesting that varying levels of coherencing operate
in all nervous systems of any significant complexity. The
reformulation also sets the stage for designing experiments to
determine more precisely the types of self-representations
nervous systems have, how they are connected to one another, and
the nature of their neural substrates.
4) In summary: The brain's earliest self-representational
capacities arose as evolution found neural network solutions for
coordinating and regulating inner-body signals, thereby
improving behavioral strategies. Additional flexibility in
organizing coherent behavioral options emerges from neural
models that represent some of the brain's inner states as states
of its body, while representing other signals as perceptions of
the external world. Brains manipulate inner models to predict
the distinct consequences in the external world of distinct
behavioral options. The self thus turns out to be identifiable
not with a nonphysical soul, but rather with a set of
representational capacities of the physical brain.
References (abridged):
1. P. M. Churchland, Matter and Consciousness (MIT Press,
Cambridge, MA, ed. 2, 1988).
2. P. S. Churchland, Neurophilosophy (MIT Press, Cambridge, MA,
1986).
3. A. R. Damasio, Descartes' Error (Grossett/Putnam, New York,
1994).
4. D. Hume, A Treatise of Human Nature (1739); modern edition by
L. A. Selby-Bigge, Ed. (Clarendon Press, Oxford, 1888).
5. G. Lakoff, M. Johnson, Philosophy in the Flesh (Basic Books,
New York, 1999).
Science 2002 296:308
Web Links: mind-body problem David Hume
Related Background Brief:
ON NON-CONSCIOUS STRATEGIC DECISIONS. Deciding advantageously in
a complex situation is thought to require overt reasoning on
declarative knowledge, namely, on facts pertaining to premises,
options for action, and outcomes of actions that embody the
pertinent previous experience. An alternative possibility was
investigated: that overt reasoning is preceded by a nonconscious
biasing step that uses neural systems other than those that
support declarative knowledge. Normal participants and patients
with prefrontal damage and decision-making defects performed a
gambling task in which behavioral, psychophysiological, and
self-account measures were obtained in parallel. Normals began
to choose advantageously before they realized which strategy
worked best, whereas prefrontal patients continued to choose
disadvantageously even after they knew the correct strategy.
Moreover, normals began to generate anticipatory skin
conductance responses (SCRs) whenever they pondered a choice
that turned out to be risky, before they knew explicitly that it
was a risky choice, whereas patients never developed
anticipatory SCRs, although some eventually realized which
choices were risky. The results suggest that, in normal
individuals, nonconscious biases guide behavior before conscious
knowledge does. Without the help of such biases, overt knowledge
may be insufficient to ensure advantageous behavior. A. Bechara
et al: Science 1997 275:1293
Related Background:
ON MIND AND BODY AND C.S. SHERRINGTON
[Charles S. Sherrington (1857-1952) loomed over early 20th
century neurobiology the way Max Planck loomed over physics.
Sherrington was awarded the Nobel Prize for Physiology and
Medicine in 1932 for his experimental work in neurophysiology.
Sherrington's remarks below on neurogenesis, made 65 years ago,
are noteworthy.]
"Much as one special organ, the heart, maintains the flow of
nutriment throughout the body, so one organ, the brain, is
provider of mind for the whole individual. If we smile at so
bald a statement, we must yet agree that it states the practical
situation with which the physician and the surgeon deal. It
shows us too the body in the grip of integration. Much of the
body has no demonstrable mind. Of the rest, most has mind only
lent to it, in the form of sensation by proxy. Such of it merely
communicates with a certain restricted piece of the body, a
particular part of a single organ, and there, so much of the
body as feels, has its sensation done for it. There too the
body's thinking seems to be done for it, namely, in the brain.
Of man we know even more confidently than of any other concrete
life that his mind is correlated with his brain. But let us
avoid the sophistication that for the mind to be in the brain is
any self-evident proposition. 'Many men', wrote Kant, 'fancy
they feel their thought in their head, but that is a mistake. No
experience tells me that I am shut up some place in my brain.'
We owe I suppose to medicine in the main the knowledge of where
in the body the 'seat of the mind', as it is termed, is. But so
far from its being a self-evident fact, one of the greatest of
biologists, Aristotle, did not subscribe to it although it was
accepted by physicians in his time... A brain cell is not
unalterably from birth a brain cell. In the embryo-frog, the
cells destined to be brain can be replaced by cells from the
skin of the back, the back even of another embryo; these after
transplantation become in their new host brain-cells and seem to
serve the brain's purpose duly. But cells of the skin it is
difficult to suppose as having a special germ of mind. Moreover,
cells, like those of the brain in microscopic appearance, in
chemical character and in provenance, are elsewhere concerned
with acts wholly devoid of mind, e.g., the knee jerk, the
light-reflex of the pupil. A knee-jerk kick and a mathematical
problem employ similar-looking cells. With the spine broken and
the spinal cord so torn across as to disconnect the body below
from the brain above, although the former retains the unharmed
remainder of the spinal cord consisting of masses of nervous
cells, and retains a number of its nervous reactions, it reveals
no trace of recognizable mind."
C.S. Sherrington: Man on His Nature: Gifford Lectures 1937-1938.
Mentor Books, New York, 1964.
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7. ON CHARGE-INDUCED DISTORTION OF CARBON NANOTUBES
Y.N. Gartstein et al (Xerox Corporation, US) discuss distortion
of carbon nanotubes, the authors making the following points:
1) Carbon nanotubes are particularly interesting nanoscopic
systems [1] whose electronic and mechanical properties have been
the subject of numerous studies and are attractive for diverse
applications [2,3]. One of the proposals is to use carbon
single-wall nanotubes (SWNTs) as electrochemically driven
electromechanical actuators. In these demonstrated devices,
large electrochemical charge injection can result from the high
surface area of nanotube assemblies [4]. The charge injection
produces the electromechanical actuation. Actuator strains of
above 1 % have been observed [3], which is about 10 times that
of ferroelectrics. This high strain indicates the potential for
obtaining order of magnitude advantages over any prior-art
actuator technologies for directly converting electrical energy
to mechanical energy. Currently available nanotube sheets and
long fibers comprise bundles of SWNTs, each bundle containing
from 30 to 100 of SWNTs of various internal geometries, or
chiral vectors (N,M) [1]: from zigzag (N,0) to armchair (N,N)
tubes. The observed actuation is likely to be an average from
different SWNTs. Improved synthetic methods are expected to
eventually make it possible to use SWNTs of selected types in
actuators [5].
2) The authors report an analysis designed to predict the
actuator strains that would result for different types of SWNTs
by studying a simplified electron-lattice model. Suppose one
adds delta(n) extra electrons per carbon atom to a SWNT. How
would interatomic distances be affected? The authors studied the
contribution to bond length changes arising from the modulation
of electron hopping integrals by lattice distortions. Since
Coulombic effects are ignored in this model, the results are
restricted to low charge injection levels. The authors
demonstrate that SWNTs exhibit quite a unique picture of
electromechanical actuation that strongly depends on (N, M). The
magnitude of the actuator response of individual carbon
nanotubes can be appreciably larger than that of graphite,
presenting an exciting opportunity of enhanced actuation.
3) In summary: To accommodate extra electrons or holes injected
into a single-wall carbon nanotube, carbon-carbon bonds adjust
their lengths. Resulting changes in carbon-nanotube length as a
function of charge injection provide the basis for
electromechanical actuators. The authors demonstrate that a key
mechanism at low injection levels, modulation of electron
kinetic energy, provides nanotube deformations that are both
anisotropic and strongly dependent on nanotube structure.
Nanotubes can exhibit both expansion and contraction, as well as
nonmonotonic size changes. The magnitude of the actuation
response of semiconducting carbon nanotubes may be substantially
larger than that of graphite.
References (abridged):
1. R. Saito, G. Dresselhaus, and M. Dresselhaus, Physical
Properties of Carbon Nanotubes (Imperial College Press, London,
1998)
2. Carbon Nanotubes: Synthesis, Structure, Properties and
Applications, edited by M. Dresselhaus, G. Dresselhaus, and P.
Avouris (Springer, Berlin, 2000)
3. R. Baughman, A. Zakhidov, and W. deHeer, Science (to be
published).
4. R. Baughman et al., Science 284, 1340 (1999)
5. R. Schlittler, Science 292, 1136 (2001)
Phys. Rev. Lett. 2002 89:045503
Web Links: carbon nanotubes
Related Background:
ON NANOWIRE BUILDING BLOCKS
Y. Huang et al (Harvard University, US) discuss nanowire
building blocks, the authors making the following points:
1) Fundamental physical constraints and economics are expected
to limit continued miniaturization in electronics by
conventional top-down manufacturing during the next one or two
decades and have thus motivated efforts worldwide to search for
new strategies to meet expected computing demands of the future.
Bottom-up approaches to nanoelectronics, where the functional
electronic structures are assembled from well-defined nanoscale
building blocks, such as carbon nanotubes, molecules, and/or
semiconductor nanowires, have the potential to go far beyond the
limits of top-down manufacturing. For example, single-walled
carbon nanotubes have been used as building blocks to fabricate
room-temperature field-effect transistors, diodes, and an
inverter that represents a key component for logic operations.
2) However, the inability to control whether such nanotubes are
semiconducting or metallic makes specific device fabrication
largely a random event and poses a serious issue for integration
beyond the single-device element level. A potential solution to
the problem of coexisting metallic and semiconductor nanotubes
involves selective destruction of metallic tubes, although such
an approach requires extensive top-down lithography and
subsequent processing to implement.
3) The authors report a bottom-up approach in which functional
device elements and element arrays have been assembled from
solution through the use of electronically well-defined
semiconductor nanowire building blocks. The authors demonstrate
that crossed nanowire p-n junctions and junction arrays can be
assembled with over 95 percent yield and with controllable
electrical characteristics, and in addition, that these
junctions can be used to create integrated nanoscale
field-effect transistor arrays with nanowires as both the
conducting channel and gate electrode. Nanowire junction arrays
have been configured by the authors as key OR, AND, and NOR
logic-gate structures with substantial gain and have been used
to implement basic computation.
Science 2001 294:1313
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8. ON CRYSTALLINE SILICON
John Robertson (University of Cambridge, UK) discusses
crystalline silicon, the author making the following points:
1) Amorphous silicon is the leading electronic material for
large-area applications, used in solar cells and in the
thin-film transistors that make up liquid-crystal displays.
However, amorphous silicon suffers from an electrical
instability that causes a gradual loss of conversion efficiency
in solar cells. There is another form of silicon,
nanocrystalline silicon, that is more stable and whose
charge-carriers (electrons and holes) are more mobile, making it
more attractive for use in these applications.
2) Amorphous silicon can be made easily by deposition from a
silane (SiH(sub4)) plasma, and nanocrystalline silicon can be
made by the same process, under slightly modified conditions.
But the exact means by which nanocrystalline silicon, rather
than amorphous silicon, forms has been the subject of debate.
S. Sriraman et al(1) propose that hydrogen atoms from the silane
plasma catalyse the rearrangement of Si–Si bonds, triggering a
solid-state transformation of the random amorphous-silicon
network into the more ordered network of nanocrystalline silicon.
3) Nanocrystalline silicon can be deposited from a silane plasma
that has been heavily diluted with hydrogen so that there is a
high concentration of atomic hydrogen in the plasma. The most
popular explanation of the deposition process has been that
nanocrystalline silicon and amorphous silicon are deposited
simultaneously, and then the atomic hydrogen etches away
amorphous silicon more quickly, leaving mostly nanocrystalline
silicon2. Once formed, the two solid phases can then only
interconvert via the gas phase. An alternative explanation is
that atomic hydrogen permeates the film of amorphous silicon,
lowering the energy barriers to the rearrangement of the silicon
network into a more stable, more ordered nanocrystalline
lattice3. But until now the precise mechanism for this process
-- given the rather unappealing name of "chemical annealing" --
has never been fully specified.
References:
1. Sriraman, S., Agarwal, S., Aydil, E. S. & Maroudas, D. Nature
418, 62-65 (2002)
2. Tsai, C. C., Anderson, G. B. & Wacker, B. J. Non-Cryst.
Solids 114, 151-153 (1989)
3. Shirai, H., Hanna, J. & Shimizu, I. Jpn. J. Appl. Phys. 30,
L679-L682 (1991)
4. Wehrspohn, R. B., Powell, M. J., Deane, S. C., French, I. D.
& Roca i Cabarrocas, P. Appl. Phys. Lett. 77, 750-752 (2000)
Nature 2002 418:30
Web Links: amorphous silicon nanocrystalline silicon
Related Background Brief:
MECHANISM OF HYDROGEN-INDUCED CRYSTALLIZATION OF AMORPHOUS
SILICON. Hydrogenated amorphous and nanocrystalline silicon
films manufactured by plasma deposition techniques are used
widely in electronic and optoelectronic devices. The crystalline
fraction and grain size of these films determines electronic and
optical properties; the nanocrystal nucleation mechanism, which
dictates the final film structure, is governed by the
interactions between the hydrogen atoms of the plasma and the
solid silicon matrix. Fundamental understanding of these
interactions is important for optimizing the film structure and
properties. The authors report the mechanism of hydrogen-induced
crystallization of hydrogenated amorphous silicon films during
post-deposition treatment with an H2 (or D2) plasma. Using
molecular-dynamics simulations and infrared spectroscopy, the
authors demonstrate that crystallization is mediated by the
insertion of H atoms into strained Si–Si bonds as the atoms
diffuse through the film. This chemically driven mechanism may
be operative in other covalently bonded materials, where the
presence of hydrogen leads to disorder-to-order transitions. S.
Sriraman et al: Nature 2002 418:62.
Related Background Brief:
DANGLING-BOND DEFECT STATE CREATION IN MICROCRYSTALLINE SILICON
THIN-FILM TRANSISTORS. The authors report an analysis of the
threshold voltage shift in microcrystalline Si thin-film
transistors (TFTs), in terms of a recently developed
thermalization energy concept for dangling-bond defect state
creation in amorphous Si TFTs. The rate of the threshold voltage
shift in microcrystalline Si TFTs is much lower than in
amorphous Si TFTs, but the characteristic energy for the
process, which the authors identify as the mean energy to break
a Si–Si bond, is virtually the same. The authors suggest this
indicates that the same basic Si–Si bond breaking process is
responsible for the threshold voltage shift in both cases. The
lower magnitude in microcrystalline Si TFTs is due to a much
lower attempt frequency for the process. The authors interpret
the attempt frequency in amorphous and microcrystalline silicon
in terms of the localization length of the electron wave
function and the effect of stabilizing H atoms being located
only at grain boundaries. R.B. Wehrspohn et al: Appl. Phys.
Lett. 2000 77:750.
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9. ON INFORMATION AND COMPUTATION
A. Galindo and M.A. Martin-Delgado (Complutense University, ES)
discuss information and computation, the authors making the
following points:
1) The twentieth century opened with Planck's (1900) discovery
of quanta, which was followed by the formulation of quantum
theory during the first few decades. As the century went by, we
witnessed a continuous increase in the applications of quantum
mechanics, beginning with atomic physics and continuing with
nuclear and particle physics, optics, condensed matter, and
countless other developments. As the century was closing a new
field of applications emerged that gave quantum physics a
refreshing twist. While it seems inevitable that physics would
be affected by the availability of more and more powerful
computers, which have revolutionized many areas of science, it
is more surprising to find that quantum physics may influence
the fields of information and computation in a new and profound
way. For instance, fundamental aspects of quantum mechanics such
as those entering Einstein, Podolsky, and Rosen (1935) states
have found unexpected applications in information transmission
and cryptography.
2) Why has this happened? It began with the realization that
information has a physical nature (Landauer, 1961, 1991, 1996).
It is imprinted on a physical support (the rocky wall of a cave,
a clay tablet, a parchment, a sheet of paper, a magneto-optic
disk, and so forth), it cannot be transmitted faster than light
in vacuum, and it abides by natural laws. The statement that
information is physical does not simply mean that a computer is
a physical object, but in addition that information itself is a
physical entity. In turn, this implies that the laws of
information transmission are restricted or governed by the laws
of physics -- in particular, those of quantum physics. In fact
these laws implying linearity, entanglement of states,
nonlocality, and the indeterminacy principle make possible new
and powerful transmission tools and information treatments, as
well as a prodigious efficiency of computation.
3) A typical computation is implemented through an algorithm in
a computer. This algorithm is now regarded as a set of physical
operations, and the registers of the quantum computer are
considered to be states of a quantum system. The familiar
operation of initializing data for a program to run is replaced
by the preparation of an initial quantum state, and the usual
tasks of writing programs and running them correspond, in the
new formulation, to finding appropriate Hamiltonians for their
time-evolution operators to lead to the desired output. This
output is retrieved by a quantum measurement of the register,
which has deep implications for the way quantum information must
be handled.
4) In summary: Quantum theory has found a new field of
application in the realm of information and computation during
recent years. The authors review how quantum physics allows
information coding in classically unexpected and subtle
nonlocal ways, as well as information processing with an
efficiency largely surpassing that of the present and
foreseeable classical computers. Quantum teleportation, dense
coding, and quantum cryptography are examples of the impact of
quanta on the transmission of information. Quantum logic gates
and quantum algorithms are instances of the improvement made
possible in information processing by a quantum computer.(1-5)
References (abridged):
1. Aharonov, D., 1998, in Annual Reviews of Computational
Physics, edited by Dietrich Stauffer (World Scientific,
Singapore), Vol. VI.
2. Aspray, W., 1990, John von Neumann and the Origins of Modern
Computing (MIT, Cambridge, MA)
3. Atkins, D., M. Graff, A.K. Lenstra, and P.C. Leyland, 1995,
in Advances in Cryptology—Asiacrypt'94: Proceedings of the 4th
International Conference on the Theory and Applications of
Cryptology, Lecture Notes in Computer Science No. 917 (Springer,
New York), p. 263.
4. Bell, J.S., 1987, Speakable and Unspeakable in Quantum
Mechanics (Cambridge University Press, Cambridge)
5. Bennett, C.H., and G. Brassard, 1984, in Proceedings of the
International Conference on Computers, Systems & Signal
Processing, Bangalore, India (Indian Institute of Science,
Bangalore, India), p. 175.
Rev. Mod. Phys. 2002 74:347
Web Links: information theory quantum computers
Related Background:
ON SILICON-BASED QUANTUM COMPUTER ARCHITECTURE
The indivisible unit of classical information is the "bit",
which takes one of two possible values, 0 or 1. Any amount of
classical information can be expressed as a sequence of bits. A
classical computer executes a series of simple operations
("gates"), each of which acts upon a single bit or pair of bits.
By executing many gates in succession, the computer can evaluate
any *Boolean function of a set of input bits. Quantum
information can also be reduced to elementary units, called
quantum bits or "qubits". A qubit is a two-level quantum system
(e.g., the spin of an electron). A quantum computer executes a
series of elementary quantum gates, each of which is a *unitary
transformation that acts on a single qubit or pair of qubits. By
executing many such gates in succession, the quantum computer
can apply a complicated unitary transformation to a particular
initial state of a set of qubits. Finally, the qubits can be
measured, the measurement outcome the final result of a quantum
computation. (J. Preskill: Physics Today 1999 June).
In this context, the term "unitary transformation" refers to a
linear operator whose adjoint is equal to its inverse. The
"adjoint" A* of an operator A is an operator such that for all f
and g in the domain of A: (Af,g) = (f,A*g). If A* = A, then A is
said to be self-adjoint.
B. Koiller et al (University of Maryland, US) discuss quantum
computers, the authors making the following points:
1) Following the proposal by Kane (1), there has been much
effort [2-4] to develop a silicon-based quantum computer
architecture. The basic ideas of the Kane proposal are simple
and attractive: to use donor nuclear spins as quantum bits
(qubits), and to utilize the vast infrastructure and technology
associated with the Si industry to fabricate precisely
controlled Si nanostructures, where exchange effects between
electrons and nuclei in neighboring donor impurities (e.g., P-31
in Si) could serve as the two-qubit gates, similar to the
electron-spin-based QC proposal by Loss and DiVincenzo [5]. The
motivation for a Si quantum computer is obvious: Once the basic
one-qubit and two-qubit operations have been demonstrated using
donor impurities in Si nanostructures, computer chip fabrication
technology associated with the existing and dominant Si industry
will easily enable the scale-up of information processing
involving a large number of donor nuclear spin qubits. Indeed,
one of the formidable stumbling blocks in developing working
quantum computer hardware has been the scale-up problem, as the
demonstrated qubits in trapped ion and liquid state NMR
techniques are not readily scalable in any significant manner.
2) A great deal of experimental work is currently aimed at
developing suitable qubits in Si nanostructures with precisely
introduced dopant impurities, using both a "top-down" approach
with ion implantation, and a "bottom-up" approach with molecular
beam epitaxy growth and scanning tunneling microscopy [4]. In
the Si quantum computer model [1,2], donor electrons act as
shuttles between different nuclear spins. For two-qubit
operations, which are required for a universal quantum computer,
both electron-electron exchange and electron-nucleus hyperfine
interaction need to be precisely controlled. These are
unquestionably formidable experimental problems. In the original
proposal, Kane used the Herring-Flicker exchange formula for two
hydrogenic centers to obtain an order of magnitude estimate of
the electron exchange among donors in Si [1]. However, as he
also pointed out, donor exchange in Si is not hydrogenic.
3) The authors report a calculation of the donor electron
exchange in silicon and germanium, and demonstrate an
atomic-scale challenge for quantum computing in Si (and Ge), as
the six (four) conduction-band minima in Si (Ge) lead to
intervalley electronic interference, generating strong
oscillations in the exchange splitting of two-donor two-electron
states. Donor positioning with atomic-scale precision within the
unit cell thus becomes a decisive factor in determining the
strength of the exchange coupling -- a fundamental ingredient
for two-qubit operations in a silicon-based quantum computer.
References (abridged):
I. B.E. Kane, Nature (London) 393, 133 (1998).
2. B. E. Kane, Fortschr. Phys. 48, 1023 (2000).
3. R. Vrijen et al., Phys. Rev. A 62, 012306 (2000).
4. J.L. O'Brien et al.. Phys. Rev. B 64, 161401 (2001).
5. D. Loss and D. P. DiVincenzo, Phys. Rev. A 57, 120 (1998).
Phys. Rev. Lett. 2002 88:027903
ScienceWeek http://www.scienceweek.com
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10. ON TIES BETWEEN PHARMACEUTICAL AND TOBACCO COMPANIES
B. Shamasunder and L. Bero (University of California San
Francisco, US) discuss ties between pharmaceutical and tobacco
companies, the authors making the following points:
1) Financial ties between companies producing addictive tobacco
products and companies producing drugs to treat or alleviate the
addiction are a potential conflict of interest. Several types of
financial ties can exist. For example, one company could be the
sole supplier of a product that is needed by another company.
Or, a company could be financially dependent on sales from
another company. Corporate diversification also results in
financial ties between companies.
2) Corporate diversification leads to a network of holding
companies, parent companies, and subsidiaries that are
financially connected but operate seemingly independently.(1,2)
Diversification can contribute to financial stability, but it
also allows corporate negotiations to occur with little public
knowledge and can hide financial ties that are potential
conflicts of interest.
3) The diversification of the tobacco industry is
well-documented.(3,4) The tobacco industry has systematically
acquired companies that manufacture unrelated consumer products
such as cookies, macaroni and cheese, candy, and
pharmaceuticals. The tobacco industry has used its financial
ties to pressure a variety of industries to oppose tobacco
control.(5) The pharmaceutical industry also maintains
diversified interests and is involved in the sale of multiple
products such as chemicals, pesticides, plastics, and
pharmaceuticals.(2) Thus, corporate diversification has resulted
in financial ties between pharmaceutical companies that market
nicotine replacement therapies (NRTs) and the tobacco industry.
4) In summary: Corporate diversification allows for well-hidden
financial ties between pharmaceutical and tobacco companies,
which can cause a conflict of interest in the development and
marketing of pharmaceutical products. The authors investigated
tobacco company documents released and posted on the Internet as
a result of the Master Settlement Agreement. The authors report
they found that these financial ties have fostered both
competition and collaboration between the tobacco and
pharmaceutical industries. The authors present 3 case studies.
One shows how tobacco companies pressured pharmaceutical
companies to scale back their smoking cessation educational
materials that accompanied Nicorette. The second shows how they
restricted to whom the pharmaceutical company could market its
transdermal nicotine patch. In the third case, the authors show
how subsidiary tobacco and pharmaceutical companies of a parent
company collaborated in the production of a nicotine-release
gum. The authors conclude that because tobacco cessation product
marketing has been altered as a result of these financial
conflicts, disclosure would serve the interest of public health.
References (abridged):
1. Markides CC. To diversify or not to diversify. Harvard
Business Review. 1997;75:93-99.
2. Krantz A. Diversification of the drug discovery process. Nat
Biotechnol. 1998;16:1294.
3. Blum A. Diversification in the tobacco industry. NY State J
Med. 1985:328-334.
4. Joossens L. Diversification is the future for many tobacco
farmers. Tob Control. 1996;5:177-178.
5. Landman A. Push or be punished: tobacco industry documents
reveal aggression against businesses that discourage tobacco
use. Tob Control. 2000;9:339-346.
J. Am. Med. Assoc. 2002 288:738
Web Links: tobacco Master Settlement Agreement
Related Background Brief:
THE SMOKE YOU DON'T SEE: UNCOVERING TOBACCO INDUSTRY SCIENTIFIC
STRATEGIES AIMED AGAINST ENVIRONMENTAL TOBACCO SMOKE POLICIES.
The authors present a review that details the tobacco industry's
scientific campaign aimed against policies addressing
environmental tobacco smoke (ETS) and efforts to undermine US
regulatory agencies from approximately 1988 to 1993. The public
availability of more than 40 million internal, once-secret
tobacco company documents allowed an unedited and historical
look at tobacco industry strategies. The analysis showed that
the tobacco industry went to great lengths to battle the ETS
issue worldwide by camouflaging its involvement and creating an
impression of legitimate, unbiased scientific research. The
authors conclude there is a need for further international
monitoring of tobacco industry-produced science and for
significant improvements in tobacco document accessibility. M.E.
Muggli et al: Am J Public Health 2001 91:1419.
Related Background Brief:
JUNKING SCIENCE TO PROMOTE TOBACCO. Despite the tobacco
industry's claims that it has changed its practices, the toll of
tobacco-related disease and death continues to grow worldwide,
and the industry continues to use a vast array of strategies to
promote its products and increase profits. The authors discuss
the ways the tobacco industry has created controversy about risk
assessment and about the scientific evidence of the health
hazards of secondhand smoke. The authors recommend that
policymakers be more vigilant and that they demand transparency
about affiliations and linkages between allegedly independent
scientists and tobacco companies. They also urge policymakers to
be prepared for new and continuing challenges posed by the
tobacco industry, because, despite the industry's claims, there
is little evidence of fundamental change in its objectives. D.
Yach and S.A. Bialous: Am J Public Health. 2001 91:1749.
ScienceWeek http://www.scienceweek.com
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11. ON RICE GENOMES
K. Livingstone and L.H. Rieseberg (Indiana University, US)
discuss rice genomes, the authors making the following points:
1) Although completion of the heavily anticipated human genome
sequence project will provide information needed to combat
inherited maladies, the recent completion of two sequences of
the rice genome [1,2] may be a far greater gift to humanity.
After all, as the Byzantine proverb states, "He who has bread
has many problems, he who has no bread has only one problem".
Because of the importance of rice and its status as a model for
all grasses, these sequences will provide a basis for future
genetic improvement of all the cereal grains, our most important
food resource. Beyond the obvious agricultural benefit, these
sequences may also provide unparalleled views of the processes
operating on DNA sequences that change the function and
organization of genes, leading to the formation of new species.
2) The two rice sequences are from subspecies that represent the
major cultivated gene pools of rice, Oryza sativa L. ssp. indica
and O. sativa ssp. japonica. The indica type is primarily grown
in China, and the Beijing Genomics Institute (BGI) determined
its sequence [1]. The japonica subspecies is preferred in Japan,
and Syngenta AG's Torrey Mesa Research Institute (TMRI)
determined its sequence [2]. These are both draft sequences,
produced by randomly sequencing small genomic bits and relying
on multiple, offset sequences to assemble the larger pieces.
3) From a functional standpoint, while each draft should contain
nearly all the genes in rice, many of the sequences identified
as genes are only predicted on the basis of different gene
detection algorithms. It will take a long time to validate the
expression of the putative genes biologically and take full
advantage of these efforts. Structurally, both drafts cover the
majority of the rice genome, but many of the intergenic regions
are missing. Consequently, each draft resembles a puzzle with
tens of thousands of pieces on the table, but only a few joined
to start to form a picture of the twelve rice chromosomes.
4) Even in a draft state, however, these sequences provide
enormous agricultural benefits. Rice is a crucial staple for
much of the world's population, and rice is also the compact key
to other grass genomes [3] . The main differences between rice
and maize, wheat, barley, and so on are that, while the same
genes are found in each species, they are in different
arrangements, amid various amounts of species-specific "junk"
DNA. The compactness of the rice genome, coupled with a known
sequence, will make identification of important genes easier. In
addition, the rice sequence provides a means for directing
searches in other grasses to the genes in a particular
chromosomal region. The TMRI group [2] has already demonstrated
the power of a focused search approach to define candidates for
a subset of agronomically important traits mapped in maize [4,5].
References (abridged):
1. Yu J., Hu S., Wang J., Wong G.K.-S., Li S., Liu B., Deng Y.,
Dai L., Zhou Y. and Zhang X. et al. (2002) A draft sequence of
the rice genome (Oryza sativa L. ssp. Indica) Science, 296:79-92
2. Goff S.A., Ricke D., Lan T.H., Presting G., Wang R., Dunn M.,
Glazebrook J., Sessions A., Oeller P. and Varma H. et al. (2002)
A draft sequence of the rice genome (Oryza sativa L. ssp.
Japonica) Science, 296:92-100
3. Devos K.M. and Gale M.D. (2000) Genome relationships: the
grass model in current research. Plant Cell, 12:637-646
4. The Arabidopsis Genome Initiative (2000) Analysis of the
genome sequence of the flowering plant Arabidopsis thaliana
Nature, 408:796-815
5. Brendel V., Kurtz S. and Walbot V. (2002) Comparative
genomics of Arabidopsis and maize: prospects and limitations.
Genome Biol, 3:1005
Current Biology 2002 12:R470
Web Links: rice genome
Related Background Brief:
GENOME RELATIONSHIPS: THE GRASS MODEL IN CURRENT RESEARCH. Ten
years ago, with the advent of comparative mapping, a new tool
became available to plant geneticists. Comparative genome
analyses demonstrated that gene orders among related plant
species remained largely conserved over millions of years of
evolution. This finding has revolutionized our thinking and
formed the basis of a new science -- comparative genomics. Since
the first comparative mapping experiments, studies of genome
relationships have included an ever wider range of plant
species, and the focus has shifted from comparisons at the gross
map level to studies of gene organization in small chromosomal
regions and finally to the DNA sequence itself. To date, the
most comprehensive data set comes from the grasses. The Poaceae
family includes the staple cereals rice, maize, wheat, barley,
sorghum, and the millets. For most of the past century, research
has proceeded on each of these species individually. Mutants
were produced, genetic maps were generated, and biochemical
pathways were unraveled. Comparative genomics has provided the
basis and stimulus to integrate this knowledge for application
to all cereal crops. The realization of the power of a
comparative approach has led to several plant genome initiatives
and has promoted rice as a model for cereal crops. The rice
genome, with only 400 million DNA base pairs (Mb), is the
smallest among the major cereal crops and only approximately
four times larger than that of the eudicot model plant
Arabidopsis. Dense genetic maps, carrying some 2500 markers,
have been constructed, and physical maps cover most of the
genome. Additionally, large public collections of expressed
sequence tags (ESTs) have become available, and it is clear that
sequence data covering the entire rice genome will add a further
vital dimension to comparative genomics in the near future. K.M.
Devosa and M.D. Galea: Plant Cell 2000 12:637.
ScienceWeek http://www.scienceweek.com
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12. ON ILLNESS AFTER INTERNATIONAL TRAVEL
E.T. Ryan et al (Harvard University, US) discuss illness and
international travel, the authors making the following points:
1) Between 20 and 70 percent of the 50 million people who travel
from the industrialized world to the developing world each year
report some illness associated with their travel.(1,2) Although
most illnesses reported by travelers are mild, 1 to 5 percent of
travelers become ill enough to seek medical attention either
during or immediately after travel, 0.01 to 0.1 percent require
medical evacuation, and 1 in 100,000 dies.(1) People who visit
family and friends while abroad and adventure travelers are at
increased risk of becoming ill during travel.(3-5) People who
visit family and friends often stay in local homes off usual
tourist routes and may have more intense exposure to pathogens
than tourists. They may also not perceive risks in the
environment that they are visiting and may forgo recommended
vaccines and chemoprophylactic regimens.
2) Although the incidence of many illnesses among travelers is
unknown, new surveillance systems (such as GeoSentinel, a system
of the International Society of Travel Medicine and the Centers
for Disease Control and Prevention [
http://www.istm.org/geosentinel/main.html ] and TropNetEurop,
the European Network on Imported Infectious Disease Surveillance
[ http://www.tropnet.net ]) are beginning to yield data
regarding travel-associated illness.
3) Approximately 3 percent of people traveling internationally
for short periods report fever, the presence of which requires
prompt attention.(1) The initial evaluation should focus on
infections that are life-threatening, treatable, or
transmissible. Careful assessment of the travel history, likely
incubation period, exposure history, associated signs and
symptoms, duration of fever, immunization status, use or nonuse
of antimalarial chemoprophylaxis, and degree of compliance with
a chemoprophylactic regimen, if used, helps to establish the
diagnosis. Determining an approximate incubation period can be
particularly helpful in ruling out possible causes of fever. For
example, if fever begins more than 21 days after a traveler's
return, then dengue, rickettsial infections, and viral
hemorrhagic fevers such as yellow fever and Lassa fever are
unlikely, regardless of the traveler's exposure history. As
indicated by the exposure history, time course of illness, and
associated signs and symptoms, initial investigations for
febrile travelers may include prompt evaluation of peripheral
blood for malaria; complete and differential blood counts;
liver-function tests; urinalysis; culture of blood, stool, and
urine; chest radiography; and specific serologic assays, such as
those for arboviruses (e.g., dengue virus), rickettsiae,
schistosomes, leptospira, and human immunodeficiency virus.
References (abridged):
1. Ryan ET, Kain KC. Health advice and immunizations for
travelers. N Engl J Med 2000;342:1716-1725
2. Newman RD, Barber AM, Roberts J, Holtz T, Steketee RW, Parise
ME. Malaria surveillance -- United States, 1999. Mor Mortal Wkly
Rep CDC Surveill Summ 2002;51:15-28
3. Mermin JH, Townes JM, Gerber M, Dolan N, Mintz ED, Tauxe RV.
Typhoid fever in the United States, 1985-1994: changing risks of
international travel and increasing antimicrobial resistance.
Arch Intern Med 1998;158:633-638
4. Update: outbreak of acute febrile illness among athletes
participating in Eco-Challenge-Sabah 2000 -- Borneo, Malaysia,
2000. MMWR Morb Mortal Wkly Rep 2001;50:21-24
5. Fatal yellow fever in a traveler returning from Amazonas,
Brazil, 2002. MMWR Morb Mortal Wkly Rep 2002;51:324-325
New Engl. J. Med. 2002 347:505
Web Links: tourist illness
Related Background Brief:
TYPHOID FEVER IN THE UNITED STATES, 1985-1994: CHANGING RISKS OF
INTERNATIONAL TRAVEL AND INCREASING ANTIMICROBIAL RESISTANCE.
Typhoid fever is a potentially fatal illness common in the less
industrialized world. In the United States, the majority of
cases occur in travelers to other countries. The authors report
they reviewed surveillance forms submitted to the Centers for
Disease Control and Prevention, Atlanta, Ga, for patients with
culture-confirmed typhoid fever between 1985 and 1994. The
Centers for Disease Control and Prevention received report forms
for 2445 cases of typhoid fever. Median age of patients was 24
years (range, 0-89 years). Ten (0.4%) died. Seventy-two percent
reported international travel within the 30 days before onset of
illness. Six countries accounted for 80% of cases: Mexico (28%),
India (25%), the Philippines (10%), Pakistan (8%), El Salvador
(5%), and Haiti (4%). The percentage of cases associated with
visiting Mexico decreased from 46% in 1985 to 23% in 1994, while
the percentage of cases associated with visiting the Indian
subcontinent increased from 25% in 1985 to 37% in 1994. The
incidence of typhoid fever in US citizens traveling to the
Indian subcontinent was at least 18 times higher than for any
other geographic region. Complete data on antimicrobial
susceptibility to ampicillin, chloramphenicol, and
trimethoprim-sulfamethoxazole were reported for 330 (13%)
Salmonella Typhi isolates. Isolates from 1990 to 1994 were more
likely than isolates from 1985 to 1989 to be resistant to any of
these antimicrobial agents (30% vs 12%; P<.001) and to be
resistant to all 3 agents (12% vs 0.6%; P<.001). The authors
conclude that American travelers to less industrialized
countries, especially those traveling to the Indian
subcontinent, continue to be at risk for typhoid fever.
Antimicrobial resistance has increased, and a quinolone or
third-generation cephalosporin may be the best choice for
empirical treatment of typhoid fever. J.H. Mermin et al: Arch
Intern Med 1998 158:633.
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