ScienceWeek

SCIENCE-WEEK - March 8, 2002 - Vol. 6 Number 10
An Email Research Digest Published Weekly Since 1997
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At the last dim horizon, we search among ghostly
errors of observations for landmarks that are
scarcely more substantial. The search will continue.
The urge is older than history. It is not satisfied
and it will not be suppressed.
-- Edwin Hubble (1889-1953)

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Section 1
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Contents of this Issue (Full reports in Section 2):
[(*) = includes background reports] 

Basic Sciences
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1. Biophysics: On DNA Packaging in Bacteriophage (*)
2. Energy Storage in Biological Systems
3. On the Acquisition of Language by Children
4. On Intracellular Protein Aggregation
5. Mapping in the Brain
6. Asymmetric Broca's Area in the Brains of Great Apes
7. A Single-Ion Nanoscopic Probe of an Optical Field
8. Chaos and Stability of the Solar System (*)
9. On the Prediction of Crystal Structure
10. Neutron-Star Superfluidity
11. On Asteroid Families
12. On Enrico Fermi (1901-1954) (*)

Praxis
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13. Cloned Cattle Can Be Healthy and Normal
14. Transmission Potential of Smallpox
15. On the Microbial Pathogen Salmonella (*)
16. On Rheumatoid Arthritis (*)
17. Imperfect Vaccines and the Evolution of Pathogen Virulence
18. Conflicts of Interest and Clinical Trials (*)
19. On Femtosecond Laser Pulse Propagation
20. Chemically Induced Electronic Excitations at Metal Surfaces
21. Using Nuclei to Store Quantum Computer Information
22. On Solid-State Lighting
23. Solid-State NMR and Supramolecular Systems
24. On Photonic Crystals and Band Gaps (*)

Miscellany
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25. In Focus: Reading the Mind of a Fish


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Section 2
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1. BIOPHYSICS: ON DNA PACKAGING IN BACTERIOPHAGE
J. Kindt et al (University of California Los Angeles, US) discuss
DNA packaging in bacteriophage, the authors making the following
points:
     1) The classic Hershey-Chase experiment of almost 50 years
ago is best known for confirming DNA as the genetic material. But
the experiment was also significant as the demonstration that a
bacterial virus (bacteriophage; phage) leaves its protein capsid
outside the cell it infects. More explicitly, upon binding to its
receptor protein in the outer membrane of the bacterial cell, the
viral capsid is opened and its DNA is injected into the bacterial
cytoplasm. Obviously, this transfer can only happen as a passive
process if the DNA is sufficiently pressurized in the capsid.
     2) For the past several decades, a great deal of
experimental work has been devoted to determining the arrangement
of "packaged" DNA in phage capsids through techniques that
include x-ray scattering, Raman spectroscopy, chemical cross-
linking, and electron microscopy. Various competing models of
packaging have been proposed in which the DNA molecule is
organized in concentric rings as a "spool", in parallel segments
joined at sharp kinks, or as a folded toroid. The most recent
electron microscopy results on bacteriophages demonstrate
concentric ring structures that lend support to a spool-like
structural motif.
     3) The underlying theoretical problem is also formidable,
because one is confronted with the statistical-mechanical
challenge of accounting for how a semiflexible and highly charged
chain can be confined in dimensions comparable to its persistence
length and yet hundreds of times smaller than its overall
(contour) length.
     4) The authors report a calculation of the forces required
to package (or acting to eject) DNA into (from) a bacteriophage
capsid as a function of the loaded (ejected length, under
conditions for which the DNA is either self-repelling or self-
attracting. Through computer simulation and analytical theory,
the authors report they find the loading force to increase more
than 10-fold (to tens of piconewtons) during the final third of
the loading process; correspondingly, the internal pressure drops
10-fold to a few atmospheres (matching the osmotic pressure in
the cell) upon ejection of just a small fraction of the phage
genome. The authors also suggest an evolution of the arrangement
of packaged DNA from toroidal to spool-like structures.
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Proc. Nat. Acad. Sci. 2001 98:13671
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Related Background:
BIOPHYSICS: ON THE PACKING OF DNA IN A VIRUS
Bacteriophages (bacterial viruses; phages) are the largest
virus group, with approximately 4000 different types isolated.
They are viruses that infect bacteria only, usually no more than
one or a few particular species of bacteria for each type of
phage, and they occur throughout the bacterial world and in all
bacterial habitats, even volcanic hot springs. Their dimensions
are on the order of 50 to 200 nanometers, depending on phage
type.
... ... D.E. Smith et al (University of California Berkeley, US)
discuss the packing of DNA in a bacteriophage, the authors making
the following points:
     1) As part of the viral infection cycle, viruses must
package their newly replicated genomes for delivery to other host
cells. Bacteriophage phi-29 packages its 6.6-micron long double-
stranded DNA into a 42 x 54 nanometer capsid by means of a portal
complex that hydrolyzes ATP. This process is remarkable because
entropic, electrostatic, and bending energies of the DNA must be
overcome to package the DNA to near-crystalline density.
     2) The authors report they use optical tweezers to pull on
single DNA molecules as they are packaged, thus demonstrating
that the portal complex is a force-generating motor. This motor
can work against loads of up to 57 piconewtons on average, making
it one of the strongest molecular motors reported to date.
Movements of over 5 microns are observed, indicating high
processivity. Pauses and slips also occur, particularly at higher
forces.
     3) The authors establish the force-velocity relationship of
the motor and find that the rate-limiting step of the motor's
cycle is force dependent even at low loads. Notably, the
packaging rate decreases as the prohead is filled, indicating
that an internal force builds up to approximately 50 piconewtons
owing to DNA confinement. The authors suggest their data indicate
that this force may be available for initiating the ejection of
the DNA from the capsid during infection of the bacterium.
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Nature 2001 413:748
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ScienceWeek 8 Mar 2002 www.scienceweek.com

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2. ON ENERGY STORAGE IN BIOLOGICAL SYSTEMS
Howard C. Towle (University of Minnesota, US) discusses energy
storage, the author making the following points:
     1) All organisms confront intermittent periods of fasting
during which energy intake is insufficient to meet energy
demands. As a consequence, mechanisms have evolved for
synthesizing and storing energy during times of caloric
sufficiency that can be used during periods of caloric
limitation. In mammals, the predominant storage form of energy is
triglycerides, which can be synthesized from fatty acids obtained
through the diet. Alternatively, fatty acids can be produced via
de novo synthesis from the metabolic intermediate acetyl-coenzyme
A (acetyl-CoA) The latter pathway is termed "lipogenesis".
     2) Although all cells can synthesize fatty acids, production
of triglycerides for energy storage occurs principally in the
liver and adipose tissue in mammals. Lipogenesis is regulated via
the acute control of key enzyme activities by means of allosteric
and covalent modifications. Moreover, the production of many
glycolytic and lipogenic enzymes is regulated in response to
dietary status, a response which is thought to be adaptive and
which occurs in large part via transcriptional regulation of
genes encoding lipogenic enzymes.
     3) Glucose, in particular, is a vital energy nutrient in
mammals and a major source of acetyl-CoA for triglyceride
production. The pancreatic hormones insulin and glucagon play a
central role in controlling glucose and fatty acid homeostasis.
Insulin promotes glucose utilization and storage as glycogen and
triglycerides. Glucagon opposes these actions and promotes
glucose production and triglyceride catabolism. In addition to
these hormonal factors, glucose has also been implicated as an
independent signal for controlling the synthesis of lipogenic
enzymes, but the intracellular mechanism by which glucose can
generate a signal to affect the transcription of lipogenic enzyme
genes is poorly understood.
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Proc. Nat. Acad. Sci. 2001 98:13476
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3. ON THE ACQUISITION OF LANGUAGE BY CHILDREN
J.R. Saffran et al (University of Wisconsin Madison, US) discuss
the acquisition of language by children, the authors making the
following points:
     1) Before infants can begin to map words onto objects in the
world, they must determine which sound sequences are words. To do
so, infants must uncover at least some of the units that belong
to their native language from a largely continuous stream of
sounds in which words are seldom surrounded by pauses. Despite
the difficulty of this reverse-engineering problem, infants
successfully segment words from fluent speech from approximately
7 months of age.
     2) How do infants learn the units of their native language
so rapidly? One fruitful approach to answering this question has
been to present infants with miniature artificial languages that
embody specific aspects of natural language structure. Once an
infant has been familiarized with a sample of this language, a
new sample, or a sample from a different language, is presented
to the infant. Subtle measures of surprise (e.g., duration of
looking toward the new sounds) are then used to assess whether
the infant perceives the new sample as more of the same or
something different. In this fashion, we can ask what the infant
extracted from the artificial language, which can lead to
insights regarding the learning mechanisms underlying the
earliest stages of language acquisition.
     3) Syllables that are part of the same word tend to follow
one another predictably, whereas syllables that span word
boundaries do not. In a series of experiments, it has been found
that infants can detect and use the statistical properties of
syllable co-occurrence to segment novel words. More specifically,
infants do not detect merely how frequently syllable pairs occur,
but rather the probabilities with which one syllable predicts
another. Thus, infants may find word boundaries by detecting
syllable pairs with low transitional probabilities. What makes
this finding astonishing is that infants as young as 8 months
begin to perform these computations with as little as 2 minutes
of exposure. By soaking up the statistical regularities of
seemingly meaningless acoustic events, infants are able to
rapidly structure linguistic input into relevant and ultimately
meaningful units.
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Proc. Natl. Acad. Sci. 2001 98:12874
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4. ON INTRACELLULAR PROTEIN AGGREGATION
R.S. Rajan et al (Stanford University, US) discuss protein
aggregation, the authors making the following points:
     1) Aggregation of proteins into insoluble intracellular
complexes and inclusion bodies is a common problem in
bioengineering and is also intimately linked to the pathogenesis
of most neurodegenerative diseases in humans. Protein aggregation
is widely viewed as non-specific coagulation of incompletely
folded or partially denatured polypeptides, driven by interaction
among inappropriately exposed hydrophobic surfaces. According to
this view, production of misfolded or denatured proteins may be
deleterious to cells by virtue of their ability to coaggregate
with and thereby trap unrelated cellular proteins that may
transiently display complementary surfaces.
     2) However, refolding studies of chemically denatured
polypeptides suggest that protein aggregation in-vitro is due to
specific intermolecular interactions among defined domains within
structured folding intermediates. Evidence of this specificity is
found in the seeding behavior of amyloidogenic proteins and in
the selectivity of aggregate formation by model proteins.
Although these studies suggest specificity in aggregation of
purified denatured proteins in dilute solution, few studies have
addressed the mechanism and specificity of protein aggregation
in-vivo. In cells, the vectorial nature of protein synthesis, the
high protein concentration, the action of molecular chaperones
and proteases, the potential for post-translational modification,
and the "molecular crowding" effect are all factors likely to
influence protein aggregation.
     3) The authors report experiments involving fluorescence
resonance energy transfer and deconvolution microscopy to
investigate the degree to which unrelated misfolded proteins
expressed in the same biological cells coaggregate with one
another. The authors report their data reveal that in cells,
protein aggregation exhibits exquisite specificity even among
extremely hydrophobic substrates expressed at very high levels.
Proteins inside cells aggregate into discrete foci that are
homogeneous with respect to a particular protein. The data
strongly suggest that intracellular nonspecific aggregation
between hydrophobic proteins does not occur.
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Proc. Natl. Acad. Sci. 2001 98:13060
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5. MAPPING IN THE BRAIN
Pasko Rakic (Yale University, US) discusses mapping in the brain,
the author making the following points:
     1) The brain can be thought of as a map in which the
position of its constituent neurons indicates what they do.
Nowhere is this more evident than in the cerebral cortex, which
consists of structurally distinct cellular (cytoarchitectonic)
areas responsible for functions as diverse as sensory perception,
motor control, and cognition.
     2) Apparently, as the cerebral cortex evolved, the number of
cytoarchitectonic areas increased and the number of sensory
representations also increased. Interest in how the map of the
cerebral cortex develops in the embryo has been sustained by the
belief that the mechanisms of development can help explain the
emergence of human mental capacity during evolution.
     3) Traditionally, it has been presumed that the embryonic
telencephalon first forms an equipotential sheet of cells that
then becomes specified by input from subcortical centers ("tabula
rasa model"). An alternative view -- derived from experimental
manipulations of cortical input to primate embryos -- is that
cells of the embryonic cerebral vesicle themselves carry
intrinsic programs for species-specific cortical regionalization
("protomap model"). According to this hypothesis, some region-
specific cytoarchitectonic features can develop independently of
input. Indeed, the prefix "proto-" emphasizes the malleable
nature of this primordial map. Within this primordial map, it is
thought that cues generated within cortical neurons attract
appropriate input and cooperatively create a final area-specific
3-dimensional organization.
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Science 2001 294:1011
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6. ASYMMETRIC BROCA'S AREA IN THE BRAINS OF GREAT APES
C. Cantalupo and W.D. Hopkins (Emory University, US) discuss
Broca's area, the authors making the following points:
     1) Brodmann's area 44 delineates part of Broca's area within
the inferior frontal gyrus of the human brain and is a critical
cerebral cortex region for speech production, being larger in the
left hemisphere than in the right hemisphere, an asymmetry that
has been correlated with language dominance of the left
hemisphere. The authors report evidence that there is a similar
asymmetry in this area, also with left-hemisphere dominance, in
three great ape species (Pan troglodytes, Pan paniscus, and
Gorilla gorilla). The authors suggest their findings indicate
that the neuroanatomical substrates for left-hemisphere dominance
in speech production were evident at least 5 million years ago
and are not unique to hominid evolution.
     2) The authors state that to their knowledge no one has
assessed whether there is any consistent left-right anatomical
asymmetry in the inferior frontal gyrus of any non-human primate,
and that this is surprising because it is known from
cytoarchitectonic and electrical stimulation studies that many
non-human primates, including the great apes, possess a homolog
of area 44.
     3) The authors suggest that whatever the function of area 44
in great apes, their finding that these species show a human-like
asymmetry, not only in posterior but also in frontal regions,
indicates that the origin of asymmetry in language-related areas
of the human brain should be interpreted in evolutionary terms
rather than being confined to the human species.
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Nature 2001 414:505
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7. A SINGLE-ION NANOSCOPIC PROBE OF AN OPTICAL FIELD
G.R. Guthoehrlein et al (Max Planck Institute for Quantum Optics
Garching, DE) discuss near-field imaging, the authors making the
following points:
     1) One of the principal goals in optical imaging is to
improve spatial resolution. Observations of the optical far field
are limited by diffraction, and structures smaller than the
wavelength of the radiation cannot therefore be resolved. This
limitation has been overcome with the method of near-field
imaging, in which a probe is brought close to the field to be
measured. In general, in near-field imaging, resolution beyond
the diffraction limit of optical microscopy is obtained by
scanning the sampling region with a probe of subwavelength size.
     2) In recent near-field imaging experiments, single
molecules have been used as nanoscopic probes to attain a
resolution of a few tens of nanometers. Positional control of the
molecular probe is typically achieved by embedding the probe in a
crystal attached to a substrate on a translational stage.
However, the presence of the host crystal inevitably leads to a
disturbance of the light field to be measured.
     3) The authors report a near-field probe with atomic-scale
resolution -- a single calcium ion in a radio-frequency trap --
that causes minimal perturbation of the optical field. The
authors report they measure the 3-dimensional spatial structure
of an optical field with a spatial resolution as high as 60
nanometers (determined by the residual thermal motion of the
trapped ion), and scan the modes of a low-loss optical cavity
over a range of up to 100 microns. The authors suggest that the
precise positioning they achieve implies a deterministic control
of the coupling between ion and field. At the same time, the
field and the internal states of the ion are not affected by the
trapping potential. The authors suggest their setup is therefore
an ideal system for performing cavity quantum electrodynamics
experiments with a single particle.
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Nature 2001 414:49
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8. CHAOS AND STABILITY OF THE SOLAR SYSTEM
R. Malhotra et al (University of Arizona, US) discuss the
stability of the Solar System, the authors making the following
points:
     1) In the early 1600s, Johannes Kepler (1571-1630) laid the
groundwork for modern celestial mechanics by discovering and
formulating the laws of planetary motion from study of the
complex observed motions of the planets. Isaac Newton (1642-1727)
subsequently achieved further simplicity in his mathematical
description of the basic laws of motion and the universal law of
gravitation. Thus, we came to a simple set of equations that
determine the motions of the planets. The force on each planet is
simply the sum of the gravitational forces from the Sun and from
all of the other planets in the Solar System.
     2) For a two-body system (Sun and one companion), there is a
simple and elegant solution to the set of equations: a conic
section (circle or ellipse, parabola or hyperbola). However, the
presence of a third body (or in the case of the Solar System, the
Sun, the 9 planets, and myriad minor bodies) allows no simple
solution to these simple equations.
     3) During the last two decades, advances in computer speed,
the development of new numerical techniques, and the application
of modern nonlinear dynamics techniques and chaos theory to
classical problems of celestial mechanics have led to the
discovery and exploration of a number of examples of dynamical
chaos in our Solar System. In its scientific usage, "chaos" is
not a synonym for disorder: rather the term refers to the
irregular behavior that can occur in deterministic dynamical
systems, i.e., systems described by ordinary differential
equations free of external random influences. Chaotic systems
have two defining characteristics: a) they show order
interspersed with randomness; and b) their evolution is extremely
sensitive to initial conditions. Chaos in the Solar System is
associated with gravitational resonances. We now understand that
the orbits of small members of the Solar System -- asteroids,
comets, and interplanetary dust -- are chaotic and undergo large
changes on geological time scales. Are the orbits of the major
planets also chaotic? The answer is not straightforward and still
unclear.
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Proc. Natl. Acad. Sci. 2001 98:12342
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Related Background:
ON CHAOS THEORY AND THE STABILITY OF OUR SOLAR SYSTEM
Ordinarily, a physical system is a system in which future states
can be predicted from prior states. But not all physical systems
exhibit such predictability. The term "chaos theory" refers to a
theory of unpredictable behavior arising in a system that obeys
deterministic laws but exhibits unpredictability. The essential
idea is that in certain systems small perturbations may produce a
cascade of larger perturbations, so that eventually the behavior
of such systems cannot be predicted from prior states no matter
if the systems appear simple and obey deterministic laws.
... ... Adam Frank (University of Rochester, US) reviews
considerations of our solar system in terms of chaos theory. The
solar system may have lost several planets, and Mercury or Mars
might be the next planets to be ejected from their orbits.
Mercury has a small but finite chance of being ejected after a
close encounter with Venus. The essential idea is that due to the
gravitational influence of the other planets, the orbit of a
planet may become more and more eccentric over time, finally
cross the orbit of another planet, with the less massive planet
ejected from the solar system. There is a slight possibility that
the orbit of Mars will someday cross the orbit of Earth, with
Mars ejected from the solar system because of its lower mass. The
author suggests that under the influence of chaos theory our
understanding of planetary motion has been considerably trans-
formed, and the solar system is no longer viewed as a stable
clock, but rather as a dynamic and infinitely complex entity.
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Astronomy 1998 May
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Related Background:
CHAOS AND COMPLEXITY
     Ilya Prigogine (Free University Brussels, BE), who received
the Nobel Prize in Chemistry in 1977 for his work in
nonequilibrium thermodynamics, was among the first theoreticians
to deal with the applications of the second law of thermodynamics
to complex systems. The second law of thermodynamics effectively
holds that physical systems tend to slide spontaneously and
irreversibly toward a state of disorder (an increase of entropy).
There is no explanation in classical thermodynamics, however, of
how complex systems can arise spontaneously from less ordered
states and maintain themselves in apparent defiance of the
tendency toward entropy. Prigogine has proposed that as long as
systems receive energy and matter from an external source,
nonlinear systems ("dissipative structures") can pass through
periods of instability and then self-organization, resulting in
more complex systems whose characteristics cannot be predicted
except as statistical probabilities. The work of Prigogine has
been influential in a wide variety of fields, ranging from
physical chemistry to biology, and this work has been fundamental
in the new disciplines of chaos theory and complexity theory.
     What is called "complexity theory" is a theory that proposes
that certain systems manifest behaviors that are completely
inexplicable by any conventional analysis of the constituent
parts of the system. These behaviors, commonly called "emergent
behaviors", apparently occur in many complex systems involving
living organisms. One example is the idea that human
consciousness is an emergent property of a complex network of
neurons in the brain. The major problem of complexity theory is
how to model such emergent behavior: how to devise mathematical
laws that allow emergent behavior to be explained and predicted.
This effort to establish a solid theoretical foundation for the
description of complex systems has attracted mathematicians,
physicists, biologists, economists, and social scientists.
     In the research context, complexity and "chaotic behavior"
are not synonymous. If one focuses attention on the time
evolution of an emergent behavior, e.g., daily changes in
temperature, that behavior may well be completely deterministic
yet indistinguishable from a random process: the behavior is
chaotic. However, although chaos is often associated with complex
systems, not all complex systems manifest chaotic behavior. From
the standpoint of systems theory, it is the interactions of
components that create emergent patterns that are important, and
not any chaotic behavior these may patterns may display.
... ... Massimo Pigliucci (University of Tennessee Knoxville, US)
presents a review of current ideas in chaos and complexity
theory, the author making the following points:
     1) The author points out that in common non-scientific usage
the term "chaos" is a synonym for randomness, for completely non-
deterministic and irregular phenomena. In mathematical theory,
however, the term "chaos" refers to a deterministic (i.e., non-
random) phenomenon characterized by special properties that make
the predictability of outcomes very difficult: chaotic behavior
is such that although it does not occur randomly, it has the
appearance of a series of random occurrences.
     2) Chaotic dynamics are usually (but not always) a property
of nonlinear systems (i.e., systems whose behavior can be
described by sets of nonlinear equations). However, the converse
is not true: not all nonlinear dynamics generate chaotic
behavior. Typically, a given system of equations can produce both
non-chaotic and chaotic outcomes, depending on the range of
values assumed by the parameters of the equations. In many
systems, one can increase the value of a key parameter and obtain
a progression of outcomes from a steady equilibrium state to
regular oscillations with two equilibria, to more complex cycles
with multiple equilibria, to finally producing the chaotic
condition.
     3) Another phenomenon typically associated with chaos is the
so-called "butterfly effect": chaos is analogous to a situation
in which the flapping of a butterfly's wings in Brazil ends up
starting a cascade of events that results in a tornado in Texas.
The term for this is "sensitivity to initial conditions": a small
perturbation of a system can cause a series of effects that
eventually lead to macroscopic consequences later in the time
sequence. Had that perturbation been of a different nature, an
entirely different series of events would have occurred. a more
formal way to describe the butterfly effect is to state that the
predictability of the system decreases exponentially with time:
our predictions of where the system will be are relatively good
for the immediate future, but lose accuracy for slightly longer
intervals of time, and are soon completely useless.
     4) In general, a chaotic system is one whose mathematical
function is characterized by at least one of the following: a)
The system has sensitive dependence on initial conditions on its
domain; and/or b) the system has a positive *Lyapunov exponent at
each point in its domain that is not eventually periodic. A
"Lyapunov exponent" is a convenient measure of how fast the
trajectories of the system diverge in *phase space: if the
exponent is negative, the system actually converges at an
equilibrium point; if the exponent is near zero, the system
behaves with periodic regularity; if the exponent is positive,
the system is either chaotic or (for very large positive
exponents) random.
     5) Chaos theory is a component of a larger but more vague
theoretical framework called "complexity theory". Essentially,
complexity theory is an attempt to study systems that satisfy two
conditions: a) the system is made of many interacting parts; b)
the interactions result in emergent properties that are not
immediately reducible to a simple sum of the properties of the
individual components. In general, complexity theory uses
nonlinear dynamical modeling to account for the behavior of
orderly complex systems. The dynamics manifested by a given
system depend fundamentally on two parameters: the number of
parts (N) that compose the system, and the average number of
connections (K) among the parts within the system. So-called "NK"
systems then fall into 3 types, depending on the relationship
between N and K:
... ... a) K very small compared to N: Number of connections very
small compared to the total number of parts: Each part behaves
essentially independently of other parts, and the properties of
the system are the properties of the individual parts. Such
systems tend to be static or reach simple dynamic equilibria, and
are sometimes called "sub-critical".
... ... b) K increasing compared to N: The dynamics becomes more
complex and emergent properties appear: Local changes propagate
to distant parts of the system as a consequence of connectivity,
but this propagation usually does not cause global change, since
the ratio of K to N is still relatively small. Such systems are
called "edge of chaos" systems, or "critical systems".
... ... c) K approaches N: Most components of the system are
connected to almost every other component: This creates the
determinate but unstable "supercritical" systems described by
chaos theory.
     In terms of Lyapunov exponents: a) subcritical NK systems
have a negative Lyapunov exponent; b) critical NK systems have a
Lyapunov exponent near zero; c) chaotic NK systems are
characterized by a positive Lyapunov exponent.
     Most classical mathematics, physics, and biology deal with
subcritical systems; chaos theory and fractal geometry deal with
supercritical systems; complexity theory focuses on critical
systems and the transition between system types. Alleged examples
of critical systems (i.e., systems on the "edge of chaos")
include the evolution of natural populations, the developmental
biology of plants and animals, the stock market, the global
economy, and the dynamics of galaxy clusters.
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Skeptic 2000 vol.8 No.3
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Notes:
... ... *Lyapunov exponent: See related background material
below.
... ... *phase space: See related background material below.
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Related Background:
THEORETICAL PHYSICS: CHAOS AND NONLINEAR DYNAMICS
     In general, a nonlinear dynamical system is a system
described by time-dependent differential equations such that the
rates of change of one or more dependent variables of the system
depend in a nonlinear fashion on the variables themselves.
Certain nonlinear dynamical systems, some of which are of great
scientific interest, exhibit "chaotic dynamics". In this context,
the term "chaos" refers to  unpredictable behavior arising in a
system that obeys deterministic laws but exhibits
unpredictability. The essential idea is that in certain systems
small perturbations may produce a cascade of larger
perturbations, so that eventually the behavior of such systems
cannot be predicted from prior states no matter if the systems
appear simple and obey deterministic laws. Examples of chaotic
nonlinear dynamical systems are the weather and populations of
organisms, and instances of chaotic dynamics have now been
documented in most scientific disciplines.
     Because the differential equations for many nonlinear
systems are often intractable (i.e., no explicit quantitative
solutions are possible), a focus of theoretical research on
nonlinear systems has been on analysis of the qualitative
behavior of such systems, in particular on analysis of the "phase
space" and "trajectories" in the phase spaces of such systems.
The idea is essentially as follows: If the state of a system
depends upon N variables, the instantaneous state of the system
can be viewed as a point (phase point) in an N-dimensional space
(phase space; system hyperspace), and as the state of the system
changes, its phase point can be viewed as describing a trajectory
in its phase space. Qualitative analysis of the possible families
of solutions of nonlinear differential equations can provide
information about such phase space trajectories, and there are
certain real systems for which qualitative analysis of the phase
space trajectories of the system has revealed significant
properties of the system otherwise difficult to delineate.
... ... J.P. Gollub and M.C. Cross (2 installations, US) present
a commentary on recent research on chaotic nonlinear dynamics,
the authors making the following points:
     1) The techniques of nonlinear dynamics are well-developed,
but the impact of this field has been largely confined to
phenomena in which there are only a few important time-dependent
quantities. Unfortunately, this excludes a vast range of
important problems in which the behavior of one point in space
can be quite different (though statistically similar) to that at
another location. A particular example is convective behavior.
     2) The traditional approach to studying nonlinear dynamical
behavior is to plot the dynamical variables of the system as a
multidimensional phase space graph indicating how the behavior
changes over time. For example, a simplified model of the Solar
System consisting of the Sun and 9 planets would require a phase
space with as many as 60 dimensions (3 position and 3 momentum
coordinates for each body). In the case of a convecting fluid, a
complete description of the flow pattern requires knowledge of
the velocity and temperature at a very large number of locations,
so the number of dimensions of the phase plot are enormous (from
thousands to millions, depending on the desired spatial
resolution). As a result, the methods of nonlinear dynamics are
cumbersome and progress has been slow, even though many
interesting examples of spatiotemporal chaos have been explored
both experimentally and numerically.
     3) Recent research (D.A. Egolf et al: Nature 404:733 2000)
involving numerical studies of an accepted model of thermal
convection indicates that the origin of unpredictable motion in
chaotic thermal convective systems, at least in one particular
form of spatiotemporal chaos, lies in what occurs in small
regions of space and over short time-scales. These local changes
in the organization of the flow affect the surrounding regions in
such a way that the entire future evolution is affected. The
authors state: "This is something akin to Ed Lorenz's famous
remark [E.N. Lorenz: J. Atmos. Sci. 20:130 1963] that the
localized flapping of a butterfly's wings might change the
weather dramatically over the entire world a few weeks later."
Although such sensitivity to localized fluctuations has never
been confirmed as the source of the unpredictability of the
weather, it is apparently the origin of chaotic dynamics in
thermal convection.
     4) The authors conclude: "The methods used by Egolf et al
should apply to many other forms of chaos in spatially extended
systems (physical, chemical, and biological) for which reliable
model equations are available, so that the key processes leading
to the complex dynamics can be identified. Applications to areas
as diverse as cardiology and atmospheric dynamics might be
expected eventually. Moreover, it is not unreasonable to imagine
that insight into the processes leading to unpredictability will
also lead to progress in modifying or controlling the dynamics of
these systems."
-----------
Nature 2000 404:710
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Related Background:
EXPERIMENTAL EVIDENCE FOR MICROSCOPIC CHAOS
In the study of physical systems, the term "chaotic behavior" has
a specific meaning: the behavior of a system is said to be
"chaotic" if its final state is so sensitive to the system's
precise initial conditions that the behavior of the system is in
effect unpredictable and cannot be distinguished from a random
process, even though the behavior of the system is strictly
determinate in a mathematical sense. In other words, a
deterministic system characterized by extremely sensitive
instabilities, despite the system being determinate, can exhibit
behavior that is unpredictable, and the system is then called
"chaotic". During the past several decades, the analysis of such
chaotic systems has intrigued both physicists and mathematicians.
In general, in the study of physical systems, the term "phase
space" refers to a multidimensional space, each point of which
(phase point) completely represents the state of the system. For
example, in the study of dynamical systems, each phase point in
the phase space completely represents the values of all the
generalized coordinates and corresponding momenta. As the phase
point of a system moves in the phase space (e.g., changes with
time), the phase point follows a trajectory in the phase space,
and this trajectory is called the "phase point trajectory". In
the mathematical analysis of a particular phase space and its
phase point trajectories, "*Lyapunov exponents" are coefficients
that describe the rates at which nearby phase point trajectories
converge or diverge, and the Lyapunov exponents can be shown to
provide estimates of how long the behavior of a dynamical system
is predictable before chaotic behavior sets in. Chaotic behavior
of a system is characterized by the existence of positive
Lyapunov exponents. ... ... Gaspard et al present the results of
an experimental study of "microscopic chaos". The authors point
out that many macroscopic dynamical phenomena, for example in
hydrodynamics and oscillatory chemical reactions, have been
observed to display erratic or random time evolution, despite the
deterministic character of their dynamics -- a phenomenon known
as "macroscopic chaos". On the other hand, it has been long
supposed that the existence of chaotic behavior in the
microscopic motions of atoms and molecules in fluids or solids is
responsible for their equilibrium  and non-equilibrium
properties. But, the authors state, this hypothesis of
microscopic chaos has never been verified experimentally. The
authors now report direct experimental evidence for microscopic
chaos in fluid systems, the study involving the *observation of
brownian motion of a colloidal particle suspended in water. The
authors report finding a positive lower bound on the sum of
positive Lyapunov exponents of the system composed of the
brownian particle and the surrounding fluid. They suggest their
results and quantitative analysis provide strong experimental
evidence for microscopic chaos. They conclude: "On the assumption
that the system is deterministic, and given our knowledge of the
molecular structure of the fluid, this evidence supports, in
particular, the hypothesis that large systems -- which may be
treated by statistical mechanics -- are typically chaotic. The
result also supports the role of dynamical instability in non-
equilibrium fluids."
-----------
Nature 1998 394:865
-----------
Notes:
... ... *Lyapunov: A.M. Lyapunov (1857-1918) developed a general
theory of dynamic stability applicable to both linear and
nonlinear systems. His work was largely buried and forgotten
until it was exhumed nearly 30 years after his death.
... ... *observation of brownian motion: The experiment here
involved a colloidal particle of 2.5 microns diameter moving in
suspension in deionized water at 22 degrees Celsius, with
recorded observations of 145,612 positions over a total time
interval of approximately 2430 seconds, the observations
involving a microscope and video camera, the smallest resolution
stated as 25 nanometers. Particles of this size undergo
sedimentation, which may confound the results with non-Brownian
effects, but the authors report studies of non-sedimenting
smaller particles substantiate their observations, the larger
particle simply allowing tracking observations for a longer time.
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9. ON THE PREDICTION OF CRYSTAL STRUCTURE
J. Pillardy et al (Cornell University, US) discuss crystal
structure prediction, the authors making the following points:
     1) Crystal structure prediction is one of the most
challenging and important problems in theoretical and applied
crystal chemistry. It plays an extremely important role in fields
in which the rational design of new organic solids is involved
(e.g., pharmaceuticals, explosives, pigments, photosensitive and
optoelectronic materials, etc.), and it is also of significance
in solving problems of crystal polymorphism.
     2) Despite much effort by many research groups during the
past 20 years, the general problem of crystal structure
prediction is far from being solved. Generally, the term "crystal
structure prediction" is understood to refer to a search for the
most thermodynamically and kinetically favorable crystal
structures for a given molecular composition without using any
experimental information. (In many cases, however, experimental
data are included implicitly in the force field or taken into
consideration by conducting the search in the most common crystal
space groups).
     3) Unfortunately, no theoretical methods capable of taking
into account the kinetic factors (conditions of nucleation and
growth, nature of solvent, etc.) have been developed. Therefore,
crystal structure prediction is currently based solely on
thermodynamic considerations coupled with the assumption that the
structure observed experimentally corresponds to the global
minimum of the free energy. However, free energy is not a
function of geometrical coordinates of a single crystal
structure. Therefore, the traditional approach to crystal
structure prediction assumes that the free energy of a crystal
can be approximated by its potential energy (which can be
computed easily), with the lowest minima corresponding to the
structures observed experimentally. In both theory and practice,
this is a far from satisfactory compromise.
-----------
Proc. Natl. Acad. Sci. 2001 98:12351
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10. ON NEUTRON-STAR SUPERFLUIDITY
N. Anderson and G.L. Comer (University of Southampton, UK)
discuss superfluidity in neutron stars, the authors making the
following points:
     1) Since their discovery in the late 1960s, neutron stars
have emerged as unique probes of many extremes of physics.
Comprising approximately 1.5 solar masses of material compressed
inside a radius of 10 kilometers, i.e., well beyond nuclear
density, the neutron stars still hide many of their mysteries.
For example, we do not yet fully understand the nature of the
supranuclear equation of state required to describe matter in the
core of neutron stars. Still, a picture has emerged in which
superfluidity plays a vital role. Theoretically, such a picture
has as its foundations the extraordinarily successful many-body
theory of Fermi liquids and the Bardeen-Cooper-Schrieffer (BCS)
mechanism that are used to describe superconductors and
superfluid helium-3. It is now generally believed that once a
neutron star cools below a few times 10^(9) kelvins (a few months
after its birth), the bulk of its core will become superfluid.
Thus, the more than 1000 observed pulsars provide useful
laboratories for studying large-scale superfluidity and truly
high-temperature superconductors.
     2) The main observational evidence for neutron-star
superfluidity is provided by the glitches (a sudden spin-up
followed by a long-term relaxation period) that have been
observed in approximately 30 pulsars. While the smaller glitches,
for example in the Crab pulsar, can be understood in terms of
spin-down induced quakes in the crust of the neutron star, this
model cannot explain the large glitches seen in bodies such as
the Vela pulsar. In general, the standard glitch model has an
apparent limited utility, and there is a need for an improved
understanding of neutron-star superfluidity and its astrophysical
manifestations.
-----------
Phys. Rev. Lett. 2001 87:241101
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11. ON ASTEROID FAMILIES
W.F. Bottke Jr. et al (Southwest Research Institute, US) discuss
asteroid families, the authors making the following points:
     1) Catastrophic collisions among large asteroids in the main
asteroid belt are believed to produce asteroid families defined
as clusters of asteroid fragments with similar proper semimajor
axes, eccentricities, and inclinations, and spectral signatures
consistent with an origin from a common parent body. As such,
prominent asteroid families (e.g., Koronis, Eos, Themis, Eunomia,
and Vesta) are natural laboratories for understanding high-
velocity impact physics, one of the principal geologic processes
affecting small bodies in the Solar System.
     2) Although the above formation scenario is straightforward,
there are still many aspects of asteroid families that we do not
yet understand. For example, up to now, the ejection velocities
of observed asteroid family members have been derived under the
assumption that the semimajor axes of these bodies have been
relatively constant since the family was created. The fragment
velocities for diameters less than 20 kilometers inferred from
this technique are typically several hundred meters per second.
Curiously, these velocities are inconsistent with ejection
velocities derived by other means. For example, numerical
experiments, which are capable of simulating hypervelocity
collisions among large asteroids, indicate that mean ejection
velocities of multikilometer fragments from family-forming
impacts are approximately 100 meters per second. Although limited
data are available to validate these simulations on large-scale
asteroid collisions, they have successfully reproduced results
ranging from laboratory impact experiments, where centimeter-
sized projectiles are shot into targets, to underground nuclear
explosions.
-----------
Science 2001 294:1693
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12. ON ENRICO FERMI (1901-1954)
Richard Mertens (University of Chicago, US) discusses Enrico
Fermi, the author making the following points:
     1) Nothing excited Fermi so much as a new problem to solve.
It hardly mattered what the problem was. A former student and
later colleague of Fermi recalls one afternoon when Fermi sat
with a group of students at a long table in Hutchinson Commons.
Fermi looked up at the dirty windows and asked: "Well, how thick
will dirt get before it falls off?" The former student states:
"He made us feel we could really calculate anything. He, of
course, could."
     2) Fermi shone brightest at Thursday afternoon seminars in
room 480 of the Institute for Nuclear Studies. That was when he
and his colleagues gathered to discuss whatever happened to be on
their minds. Faced with a problem that stumped other physicists,
Fermi would often turn to the blackboard, pick up a piece of
chalk, and solve the problem with ease. The astrophysicist Roger
W. Hildebrand recalls the day when a colleague wanted to know if
the age of water at the bottom of the ocean could be explained by
the churning of surface waves. Fermi said, "Let's see if we can
work it out." And he did. He did it using characteristics of
monster ocean waves that he had learned on a transatlantic
voyage. "The oceanographers at La Jolla had worked on it for
three months. Fermi worked it out on the blackboard in 15
minutes."
     3) Part of Fermi's gift as a scientist, as well as his
effectiveness as a teacher and his appeal as a human being, lay
in his simplicity. He did not care for fancy solutions. He would
explain a difficult problem so clearly that he made the answer
seem obvious. That was the way it was with Fermi.
-----------
University of Chicago Magazine 2001 December
----------
Related Background:
IN FOCUS: ON THERMODYNAMICS
"Thermodynamics is mainly concerned with the transformations of
heat into mechanical work and the opposite transformations of
mechanical work into heat. Only in comparatively recent times
have physicists recognized that heat is a form of energy that can
be changed into other forms of energy. Formerly, scientists had
thought that heat was some sort of fluid whose total amount was
invariable, and had simply interpreted the heating of a body and
analogous processes as consisting of the transfer of this fluid
from one body to another. It is therefore noteworthy that on the
basis of the heat-fluid theory [Nicolas Sadi] Carnot [1796-1832]
was able, in the year 1824, to arrive at a comparatively clear
understanding of the limitations involved in the transformations
of heat into work, that is, of essentially what is now called the
second law of thermodynamics. In 1842, only eighteen years later,
J[ulius] R. Mayer [1814-1878] discovered the equivalence of heat
and mechanical work, and made the first announcement of the
principle of the conservation of energy (the first law of
thermodynamics). We know today that the actual basis for the
equivalence of heat and dynamical energy is to be sought in the
kinetic interpretation, which reduces all thermal phenomena to
the disordered motions of atoms and molecules. From this point of
view, the study of heat must be considered as a special branch of
mechanics: the mechanics of an ensemble of such an enormous
number of particles (atoms or molecules) that the detailed
description of the state and the motion loses importance and only
average properties of large numbers of particles are to be
considered. This branch of mechanics, called 'statistical
mechanics', which has been developed mainly through the work of
[James Clerk] Maxwell [1831-1879], [Ludwig] Boltzmann [1844-
1906], and [Josiah Willard] Gibbs [1839-1903], has led to a very
satisfactory understanding of the fundamental thermodynamical
laws. But the approach in pure thermodynamics is different. Here
the fundamental laws are assumed as postulates based on
experimental evidence, and conclusions are drawn from them
without entering into the kinetic mechanism of the phenomena.
This procedure has the advantage of being independent, to a great
extent, of the simplifying assumptions that are often made in
statistical mechanical considerations. Thus, thermodynamical
results are generally highly accurate. On the other hand, it is
sometimes rather unsatisfactory to obtain results without being
able to see in detail how things really work, so that in many
respects it is very often convenient to complete a
thermodynamical result with at least a rough kinetic
interpretation. The first and second laws of thermodynamics have
their statistical foundation in classical mechanics. In recent
years, [Walther] Nernst (1864-1941] has added a third law which
can be interpreted statistically only in terms of quantum
mechanical concepts."
-----------
Enrico Fermi: _Thermodynamics_
(Lectures at Columbia University [US] 1937, Dover Publ. 1956.
From the introduction, p.ix.)
-----------
[Editor's note: Fermi gives Mayer's name as R.J. Mayer, which
reverses the initials and is an error. It is interesting that 
the discoverer of the first law of thermodynamics and the law of 
conservation of energy was not a physicist but a physician, a
medical doctor without professional training in physics. When
Mayer submitted a paper on the subject to the _Annalen der
Physik_, the submission was not even acknowledged and was thrown
away. Finally, in 1842, the noted chemist Justus von Leibig
accepted the paper for his journal _Annalen der Chemie_ und
Pharmazie. But once published, the paper was totally ignored,
Mayer became depressed, and in 1849 he attempted suicide by
jumping from a 3rd-story window. The suicide attempt failed and
Mayer became permanently lame as the result of leg injuries. By
1851, Mayer was in a mental institution, and he suffered greatly
under the primitive and cruel methods of treatment of the
mentally ill. He was eventually released, but he never fully
recovered, and he languished in obscurity: when, in 1858, Leibig
lectured on Mayer's views, Leibig referred to Mayer as deceased.
Then, in the 1860s, recognition finally arrived for Mayer's work,
and he received many honors, including the Copley Medal of the UK
Royal Society in 1871. Mayer clearly anticipated James Joule
(1818-1889) and Hermann von Helmholtz (1821-1894) in the
discovery of the law of conservation of energy.]
-----------
ScienceWeek 2001 12 Jan
ScienceWeek 8 Mar 2002 www.scienceweek.com

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13. CLONED CATTLE CAN BE HEALTHY AND NORMAL
R.P. Lanza et al (Advanced Cell Technology, US) discuss cloned
cattle, the authors making the following points:
     1) The possibility of cloning humans has raised questions as
to whether nuclear transfer can be used to reproducibly generate
healthy adult animals. Reports in the popular and scientific
press on genetic, immunological, and other developmental problems
raise the question of whether there are "any normal clones in
existence".
     2) The authors evaluated a series of 24 surviving sexually
mature cattle successfully cloned from nonquiescent somatic cells
as described in reports in 1998 and 2000. Results of physical
examination were normal for all animals, including objective
(temperature, pulse, respiratory rate) and subjective (general
appearance, eyes, lymph nodes, and cardiac and pulmonary
auscultation) findings. Results of abdominal palpation of
reproductive and gastrointestinal organs and kidneys were normal.
Social interaction and behavior of the cloned animals are normal.
They have normal conditioned responses such as reacting to farm
equipment used for feeding. They have developed a social
dominance hierarchy and the full spectrum of behavioral traits.
The cloned animals exhibited puberty at the expected age and body
weight. Conception rates after artificial insemination have been
excellent, and two of the cloned animals have give birth to
calves that appeared normal in every respect.
     3) Consistent with published reports, several of the cloned
calves experienced pulmonary hypertension and respiratory
distress at birth and fever after vaccination at 4 months.
However, the authors report they did not observe genetic defects,
immune deficiencies, gross obesity, or other drastic
abnormalities cited by other researchers. The authors suggest it
remains to be determined whether such abnormalities occur in
other species and/or are due to differences in nuclear transfer
techniques.
-----------
Science 2001 294:1893
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14. TRANSMISSION POTENTIAL OF SMALLPOX
In general, the term "herd immunity" refers to the resistance to
invasion and spread of an infectious agent in a group or
community based on the resistance to infection of a high
proportion of individuals members of the group.
... ... R. Gani and S. Leach (Center for Applied Microbiology and
Research, UK) discuss transmission of smallpox, the authors
making the following points:
     1) Despite eradication, smallpox still presents a risk to
public health as long as laboratory stocks of virus remain. One
factor crucial to any assessment of this risk is R*, the average
number of secondary cases infected by each primary case. However,
recently applied estimates have varied too widely (from 1.5 to
20) to be of practical use, and often appear to disregard
contingent factors such as socio-economic conditions and herd
immunity.
     2) The authors report a use of epidemic modeling to
demonstrate a more consistent derivation of R*. In isolated pre-
20th century populations with negligible herd immunity, the
numbers of cases initially rose exponentially, with an R* between
3.5 and 6. Before outbreak controls were applied, smallpox also
demonstrated similar levels of transmission in 30 sporadic
outbreaks in 20th century Europe, taking into account pre-
existing vaccination levels (approximately 50 percent) and the
role of hospitals in doubling early transmission. Should smallpox
recur, such estimates of transmission potential (R* from 3.5 to
6) predict a reasonably rapid epidemic rise before the
implementation of public health interventions, because little
residual herd immunity exists now that vaccination has ceased.
     3) The authors suggest that although their estimate for
smallpox represents a relatively modest transmission rate by
comparison with some other infectious diseases such as measles or
chickenpox, significant epidemics could result, particularly if
there were delays in detecting the first cases or in setting up 
effective public health interventions.
-----------
Nature 2001 414:748
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15. ON THE MICROBIAL PATHOGEN SALMONELLA
     Salmonella (named after Daniel E. Salmon, pathologist [1850-
1914]) is a genus of gram-negative rod-shaped bacteria various
species of which cause food poisoning (salmonellosis), typhoid
fever, paratyphoid fever, and some forms of gastroenteritis in
humans.
     In general, the term "serovar" (serotype) refers to a
subdivision (strain) of a group or species or subspecies
distinguishable from other strains in the group on the basis of
immune responses of a host to the strain, i.e., on the basis of
differences in strain antigens.
... ... J.H. Brumell et al (University of British Columbia, CA)
discuss Salmonella, the authors making the following points:
     1) Many pathogenic microbes establish infection by
colonizing and entering cells, and each invasive pathogen has a
particular strategy for intracellular survival. For example, some
pathogens escape the phagosome (intracellular digestive vacuole)
and replicate in the nutrient-rich cytosol, while others alter
the trafficking of their vacuolar niche to avoid antimicrobial
agents elsewhere in the cell. Salmonella is a well-studied
example of the latter strategy, altering endocytic trafficking of
its vacuole in order to survive and replicate in host cells
during disease.
     2) The estimated 2200 different serovars of Salmonella can
infect most animals, with the outcome of infection determined by
the genetic complement and fitness of both the infecting
Salmonella serovar and its host. Salmonella enterica serovar S.
typhomurium is a leading cause of gastroenteritis (food
poisoning) in humans, and causes a systemic disease resembling
typhoid fever in genetically susceptible mice, making it a
powerful model for the study of both diseases. Infections are
initiated by the consumption of contaminated food or water, after
which the bacteria breach the epithelial barrier of the small
intestine and enter the bloodstream to colonize the liver,
spleen, and other tissues. During this conquest of the host, S.
typhimurium occupies an intracellular niche and is protected from
cell-impermeant antibiotics. How this pathogen can perform such a
feat during its interactions with many diverse cell types of the
host is an important and hotly debated question. Recent studies
have demonstrated that the fate of the intracellular vacuole
containing the pathogen is different in various cell types.
-----------
Current Biology 2002 12:R15
-----------
Related Background:
VIRULENCE OF ANTIBIOTIC RESISTANT SALMONELLA
Bjorkman et al (3 authors at 2 installations, SE) report a study
of the virulence of antibiotic resistant Salmonella typhimurium.
During the last decade there has been an alarming increase in the
appearance of antibiotic-resistant bacteria as a result of an
increased use of antibiotics combined with the exceptional
ability of bacteria to develop resistance. One strategy to
reverse this development is to decrease the use of antibiotics to
promote the disappearance of the resistant bacteria present in
human and environmental reservoirs. Implicit in this reasoning is
that mutated resistant bacteria will be less viable in an
antibiotic-free environment. An associated question is whether
resistant bacteria with reduced or no virulence might accumulate
compensating mutations that restore fitness and virulence without
loss of resistance. In this study, the authors examined the
fitness of S. typhimurium in mice, and their results indicate
that most resistant mutants are less virulent than the wild type,
but that the avirulent mutants rapidly accumulate various types
of compensating mutations that restore virulence to wild-type
levels without loss of high-level resistance. The authors suggest
that if their results are general and apply to other medically
relevant pathogens, then the strategy of getting rid of
antibiotic resistant bacteria by a decreased use of antibiotics
may not be successful.
-----------
Proc. Nat. Acad. Sci. US 31 1998 95:3949
-------------------
Related Background:
EMERGENCE OF MULTI-DRUG-RESISTANT SALMONELLA IN THE US
Strains of salmonella that are resistant to antimicrobial agents
have become a worldwide health problem, with a distinct strain of
Salmonella enterica serotype typhimurium becoming a major cause
of illness in humans and animals in Europe, especially in the UK.
Glynn et al (6 authors at 2 installations, US) report an analysis
of data collected in the US by local and state health departments
and public health laboratories between 1979 and 1996 in national
surveys of the antimicrobial-drug resistance of salmonella. The 5
drugs involved were ampicillin, chloramphenicol, streptomycin,
sulfonamides, and tetracycline. The authors report that the
prevalence of S. typhimurium resistance to the 5 antibiotics
increased from 0.6% in 1979-1980 to 34% in 1996, and they
conclude that multi-drug resistant S. typhimurium has become a
widespread pathogen in the US. The authors suggest that more
prudent use of antimicrobial agents in farm animals and more
effective disease prevention on farms are necessary to reduce the
dissemination of this bacterial mutant and to slow the emergence
of resistance to additional antimicrobial agents in this and
other strains of salmonella.
-----------
New Engl. J. Med. 1998 338:1333
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16. ON RHEUMATOID ARTHRITIS
D.S. Pisetsky and E.W. St.Clair (Duke University, US) discuss
rheumatoid arthritis, the authors making the following points:
     1) Rheumatoid arthritis is a chronic inflammatory arthritis
involving 0.5 to 1 percent of the US population. This disease
affects women twice as often as men and its incidence rises with
increasing age. In general, rheumatoid arthritis causes a
symmetric polyarthritis affecting large and small joints in
association with systemic manifestation such as morning
stiffness, fatigue, and weight loss. Although considered a joint
disease, rheumatoid arthritis can have widespread effects on the
entire body and can impair life expectancy by as much as 5 to 10
years. With progressive disease, patients with rheumatoid
arthritis develop work disability, functional impairment, and
radiographic evidence of joint damage.
     2) The management of rheumatoid arthritis has undergone a
revolution in the past decade, reflecting a growing armamentarium
of drugs and a shift in treatment strategies. While rheumatoid
arthritis is a chronic condition, joint damage occurs at onset
for many patients. Thus, in the current treatment strategy, which
has replaced the older and more gradualist treatment scenario,
therapy is begun immediately to control disease activity, reduce
functional impairment, and prevent irreversible changes in
cartilage and bone.
     3) Although designated an inflammatory arthritis, rheumatoid
arthritis produces a more complicated lesion of the synovium, a
lesion composed of inflammation, cell proliferation, and
destruction of cartilage and bone. By mechanisms as yet unknown,
sustained inflammation stimulates synovial cell proliferation,
forming "pannus", an expansive and aggressive tissue that erodes
cartilage and bone. Therapy in rheumatoid arthritis thus requires
agents that block inflammation, retard synovial cell
proliferation, and prevent joint erosion. Since cell
proliferation is linked to inflammation, agents that limit immune
responses may affect the entire process.
-----------
J. Am. Med. Assoc. 2001 286:2787
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Related Background:
ENBREL AND RHEUMATOID ARTHRITIS
Rheumatoid arthritis is a chronic syndrome characterized by
inflammation of peripheral joints, with a potential for
destruction of various joint structures. The cause is unknown. A
genetic predisposition has been identified, but it is believed
that environmental factors also play a role. Approximately 1
percent of populations worldwide are affected, women 2 to 3 times
more often than men. Onset of the disease may be at any age, but
is most often at 25 to 50 years of age. The relatively new drug
Enbrel (etanercept), which has had considerable success in the
clinical treatment of rheumatoid arthritis, is a complicated
entity. It is a dimeric fusion protein consisting of 934 amino
acids with a molecular weight of approximately 150 kilodaltons.
Enbrel is essentially part of a tumor necrosis factor receptor
coupled with part of an immunoglobulin molecule, the complete
entity produced by genetic engineering of Chinese hamster ovarian
cells. _BusinessWeek_ now points out that Enbrel is an example of
how explosive corporate growth can be a mixed blessing. When
Enbrel was first launched by its developer, Immunex Corporation,
demand for the drug caught the company off guard, and without
adequate manufacturing capacity, Immunex was forced to pull the
drug from the market while it retooled its factories. Sales of
Enbrel jumped from $367 million in 1999 to $652 million in the
year 2000, which apparently broke a record for a biotech drug in
its first 24 months after launching. Apparently only 75,000 of
the 1 million patients who might benefit from the drug can get
access to it, which leaves the door open to competitors.
-----------
BusinessWeek 2001 13 August
----------
Related Background:
RHEUMATOID ARTHRITIS: A HUMAN PARVOVIRUS AS A CAUSATIVE AGENT
Rheumatoid arthritis is a disease of unknown etiology affecting
approximately 1 percent of the population worldwide. The disease
produces a long-term destruction of connective tissue that has
been considered to result from the body rejecting its own tissue
cells (autoimmune reaction). Inflammation of the synovial
membranes that line the joints is coupled with increased release
of synovial fluid, producing a thickening of the synovial
membrane, swelling of the joints, and in severe cases, soft
tissue tumors and bone and cartilage destruction. Supplementing
consideration of the disease as an autoimmune reaction, many
studies have suggested the role of an infective agent in the
etiology, and one of the suspects for such an agent is a virus,
because viral infections such as rubella (German measles), *human
parvovirus B19 (B19), cytomegalovirus (CMV), human *T-cell
leukemia virus I, and HIV (human immunodeficiency virus) often
cause an acute onset of *polyarthritis. Some cases with acute B19
infection are well known to present clinical symptoms resembling
rheumatoid arthritis, and the presence of B19 DNA has been
demonstrated in several autoimmune diseases, including rheumatoid
arthritis. ... ... Takahashi et al (10 authors at Tohoku
University, JP) now report the detection of human parvovirus B19
DNA in the synovial tissues in 30 of 39 patients with rheumatoid
arthritis, and infrequently in patients with osteoarthritis and
traumatic joints. The authors report the target cells of B19 were
*macrophages, *follicular dendritic cells, T cells, and *B-cells,
but not synovial lining cells. The authors hypothesize that B19-
positive T-cells and macrophages infiltrate into the synovium and
recruit circulating *immunocytes, that synovial T-cells and
macrophages continuously activated by B19 secrete one or more
*cytokines that stimulate a variety of synovial cells, and this
leads to an excessive synthesis of inflammatory cytokines and
*proteolytic enzymes and finally causes the destructive
alteration of the joints.
-----------
Proc. Nat. Acad. Sci. 1998 95:8227
-----------
Notes:
... ... *human parvovirus B19: This is a recently discovered
virus, the pathogen of the disease erythema infectiosum, an acute
viral disease characterized by mild constitutional symptoms and a
spreading rash that begins on the cheeks. Localized outbreaks of
the disease are common among children and adolescents.
... ... *T-cell: (lymphocyte) Lymphocytes are a type of leukocyte
(white blood cell) responsible for the immune response. There are
two classes of lymphocytes: 1) the B-cells, when presented with a
foreign chemical entity (antigen), change into antibody producing
plasma cells; and, 2) the T-cells interact directly with foreign
invaders such as bacteria and viruses.
 ... ... *polyarthritis: Simultaneous inflammation of several
joints.
... ... *macrophages: Macrophages are amoeba-like leukocytes that
are able to surround and digest foreign entities such as bacteria
and protozoa.
... ... *follicular dendritic cells: In general, a follicle is a
small secretory cavity or sac. Dendritic cells are mononuclear
cells with long cytoplasmic processes. They function as antigen-
trapping and antigen-presenting cells (antigen: a substance
foreign to the vertebrate host and capable of eliciting an immune
response). The shape of dendritic cells is "tree-like", hence
their name. They should not be confused with nerve cells, many of
which also have a "tree-like" shape, with processes called
"dendrites".
... ... *B-cells: (see *T-cell above)
... ... *immunocytes: A general term referring to any
immunologically competent leukocyte.
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. Certain cytokines are endogenous,
and need to be controlled by cell regulatory mechanisms. When
these mechanisms fail, endogenous cytokines may be implicated in
serious human diseases such as rheumatoid arthritis (as presented
in this report), where apparently deregulated cytokines cause the
inflammatory response that produces the symptoms. As a promoter
of cell growth and division, a cytokine acts as a messenger to
cells, and the transmission of the message requires a binding of
the cytokine molecule to a cytokine-specific receptor on the cell
surface. This receptor is either a protein or a protein complex
or a part of a protein.
... ... *proteolytic enzymes: A general term for enzymes that
cause the breakdown of proteins via the hydrolysis of peptide
bonds.
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ScienceWeek 8 Mar 2002 www.scienceweek.com

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17. ON IMPERFECT VACCINES AND THE EVOLUTION OF PATHOGEN VIRULENCE
S. Gandon et al (University of Edinburgh, UK) discuss imperfect
vaccines, the authors making the following points:
     1) Vaccines rarely provide full protection from disease.
Nevertheless, partially effective ("imperfect") vaccines have
been used to protect both individuals and whole populations. In a
theoretical analysis, the authors studied the potential impact of
different types of imperfect vaccines on the evolution of
pathogen virulence (induced host mortality) and the consequences
for public health.
     2) The authors report an analysis demonstrating that
vaccines designed to reduce pathogen growth rate and/or toxicity
diminish selection against virulent pathogens. The subsequent
evolution leads to higher levels of intrinsic virulence and hence
to more severe disease in unvaccinated individuals. This
evolution can erode any population-wide benefits such that
overall mortality rates are unaffected, or even increase, with
the level of vaccination coverage. In contrast, infection-
blocking vaccines induce no such effects, and can even promote
selection for lower virulence.
     3) The authors point out that like drug resistance, the
clinically detrimental evolution demonstrated in their study of
vaccines will occur on timescales longer than those of clinical
trials. Marked increases in virulence of some viral diseases have
already followed widespread use of anti-growth-rate vaccines in
the chicken industry.
     4) The authors suggest their findings have policy
implications for the development and use of vaccines that are not
expected to provide full immunity, such as candidate vaccines for
malaria.
-----------
Nature 2001 414:751
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18. CONFLICTS OF INTEREST AND CLINICAL TRIALS
K. Morin et al (American Medical Association, US) discuss
conflicts of interest in the conduct of clinical trials, the
authors making the following points:
     1) The interaction between medical research and for-profit
corporations is not new, but it has expanded considerably in
recent years. Some of the recent trends may accelerate the
research process, particularly when large clinical trials are
required. However, a renewed commitment to the application of
high ethical standards is essential to ensure that societal trust
in research is not eroded, that subjects enrolled in trials do
not become merely a means to an end, and that medical research is
efficiently translated into clinical advances that will benefit
future patients.
     2) The authors focus on the analysis of conflicts of
interest in the conduct of clinical trials in both academic and
community-based settings. Specifically, the authors discuss a)
how the roles of research scientists and clinical practitioners
differ, and b) the importance of ensuring that the consent of
participants to enroll in clinical trials is not the result of
confusion about the goals of an experimental treatment that may
resemble clinical care. The authors also discuss the potential
conflicts of interest that can arise when clinicians stand to
gain from enrolling their own patients as subjects in clinical
trials, and they examine various instances in which disclosure of
information regarding funding and compensation may serve to
minimize such conflicts.
     3) The authors emphasize that to preserve the integrity of
research and to protect the welfare of human subjects who enroll
in trials, physicians should have adequate training in the
conduct of research and be familiar with the ethics of research.
When a physician has treated or continues to treat a patient who
is eligible to enroll as a subject in a clinical trial conducted
by the same physician, someone other than the treating physician
should obtain the informed consent of the participant. The
authors also discuss the problem of disclosure of financial
incentives and related funding issues.
-----------
J. Am. Med. Assoc. 2002 287:78
-----------
Related Background:
ON CONFLICTS OF INTEREST IN MEDICAL RESEARCH
Arnold Relman (Harvard University), former editor of the New
England Journal of Medicine, discusses journal policies toward
conflicts of interest in research. Thirteen medical journals
recently published a joint editorial accusing the drug companies
of exerting an unhealthy control over research results and data
from work that they fund, and subjecting scientists to draconian
rules on the reporting of their work. The author suggests the
editorial does not go far enough: it is too restrained, too
measured. Firstly, the editorial fails to point out that the
entire system of clinical investigation is driven by profit. This
is a dramatic and unfortunate development of the past decade or
so, and it is creating unacceptable conflicts of interest for the
institutions that accept support from the pharmaceuticals
industry, for the investigators who accept benefits such as
financial incentives or consulting contracts in addition to
backing for their research, and for the companies themselves. The
author suggests the editorial fails to emphasize that we are
seeing the corruption of a system of research that used to have
high ideals and be clearly in the public interest. Secondly, the
author suggests the editors maintain that the best way to deal
with conflicts of interest is by disclosing them. Presumably, the
implication is that we can then live with it as everybody knows
what is going on. The author suggests that is foolish, and that
editors should refuse to publish research results where such
conflicts exist.
-----------
New Scientist 2001 22 Sep
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Related Background:
EFFECTS OF COMMERCIALIZATION ON RESEARCH
G. Laver et al (Australian National University, AU) discuss the
effects of commercialization on research. The authors suggest
that Australian universities are now in a dangerous state, mainly
because they have had little or no increase in real funding since
1996. Lacking a tradition of private endowments, Australian
universities are being encouraged to an unprecedented degree to
seek commercial finance for projects. The authors suggest that
commercialization of basic research will never lead to a
"knowledge nation", and basic research will not flourish in a
commercial environment when profit dictates the direction of
science. The influenza drug Relenza was not invented by a
pharmaceutical company, but resulted from years of curiosity-
driven basic research in publicly-funded institutions in
Australia and other countries. These discoveries were then
commercialized by GlaxoWellcome. The authors state that in their
experience commercialization of university research leads to a
diminution in the free flow of ideas, a focus on more applied
projects, and serious conflicts of interest. To address the
problems inherent in university research driven by commercial
considerations, we need to identify the conditions required for
good science to flourish. Good scientific research is not done by
corporations, or by the strategic teams beloved of politicians
and administrators, but through ideas which develop in the minds
of individual scientists. Of course scientific discoveries made
in universities should be developed for commercial use. The ideal
situation is vastly increased government support for curiosity-
driven basic research and a mechanism to commercialize any
discoveries made in this way.
-----------
Nature 2001 412:765
-----------
Related Background:
CORPORATE PAYMENTS TO SCIENTISTS FOR LETTERS TO JOURNALS
A blatant instance of corporate pressure in science was recently
revealed when a newspaper, the *St. Paul Pioneer Press* of St.
Paul, Minnesota (US), reported that more than a dozen scientists
received US$156,000 from the tobacco industry to write letters to
scientific journals disputing the carcinogenic effects of second-
hand smoke. The report was based on confidential industry
documents produced in a current litigation. Among the scientific
journals involved were the *Journal of the National Cancer
Institute*, *Journal of the American Medical Association*, *The
Lancet*, and *Pediatrics*. The authors were paid US$2250 to
US$10,000 per letter by the Tobacco Institute, and apparently two
law firms representing the industry revised some letters before
submission to the journals. According to the examined documents,
the strategy of the Tobacco Institute focused on recruiting
scientists "at or near retirement with no dependence on grant-
dispensing bureaucracies." Some of the journal editors involved
are apparently unconcerned, stating that what is important is
whether the content of a letter is solid. However, Richard
Horton, editor of *The Lancet*, says his reaction is one of
"disgust", and that the writing of such letters is "at best
unethical and at worst an example of research misconduct." 
Cardiologist Stanton Glantz (University of California San
Francisco, US) says of the tobacco industry letters: "They are
basically building up a record they could use for political and
legal purposes." One now wonders what corporate groups aside from
the tobacco industry have been promoting by generous financial
inducements the writing of letters by scientists to scientific
journals on other scientific topics of legal, political, or
commercial significance.
-----------
Nature 1998 394:609
-----------
Related Background:
NEW STUDY FINDS CORPORATE GIFTS IMPLY CORPORATE CONTROL
Blumenthal et al (2 installations, US) report an anonymous survey
of 2167 scientists working at 50 research-intensive universities
in the US. More than half of the university scientists who
received gifts of research material from pharmaceutical companies
or biotechnology companies report that the donors expect to exert
influence over their work, including review of academic papers
before publication, and retention of patent rights for commercial
discoveries. This is apparently the first study to examine
relations between commercial interests that give gifts of
research materials and the scientists who receive them. Unlike
research grants and contracts, gifts to US scientists are largely
unregulated by universities and are usually dismissed as
insignificant. Christopher Scott, director of research
development for the Stanford University Medical Center, says:
"There has been, in essence, a gray market of research based on
gifts for many, many years."
-----------
J. Am. Med. Assoc. 1998 1 Apr
New York Times 1998 1 Apr 98
-----------
Related Background:
INTIMIDATION OF RESEARCHERS BY SPECIAL INTEREST GROUPS
A recent issue of the highly respected New England Journal of
Medicine includes a 5 page exchange of letters on the subject of
intimidation of researchers by special interest groups. The
letters concern three different special interest-clinical science
entanglements: 1) a research study of multiple chemical
sensitivity; 2) the public health hazard of a marketed chemical
(tryptophan) product; 3) a clinical investigation of the outbreak
of interstitial lung disease among workers in a nylon flocking
plant. The first situation involves an accusation of attacks
against a researcher by special interests opposed to the
researcher's published results; the second situation involves an
accusation of peer review corruption by a large corporate entity
confronted with a billion-dollar damage suit; the third situation
involves an accusation of censorship and harassment of a medical
specialist by a manufacturing plant, a medical school
administration, and a hospital. These are all complicated
entanglements, and one cannot do full justice to them in a few
hundred words. But all parties on both sides of the issues
present their views, and these 5 pages of letters provide a
textbook illustration of the problems existing at the societal
interfaces of science. The letters are in response to an article
on the subject by Richard A. Deyo et al that appeared in NEJM on
April 14, 1997 (336:1176).
-----------
New Engl. J. Med. 1997 30 Oct
-----------
Related Background:
ACADEMIC JOURNAL REVISITS CORPORATE CORRUPTION OF SCIENCE
*Lingua Franca*, a highly respected general academic journal, has
published a review of some recent history in the arena of
corporate corruption of science and scientific research. The
fundamental problem is simply stated: Some corporations fund
scientific research with expectations, often contractual, of
control of publication and the final wording of conclusions in
the resultant papers. Several prestigious journals still do not
require scientists who report research results to reveal any
connections to interests that might profit from their
conclusions. But most of the scientific community is determined
to put an end to any corruption. The story is still to be played
out.
-----------
Lingua Franca June/July 1997
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ScienceWeek 8 Mar 2002 www.scienceweek.com

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19. ON FEMTOSECOND LASER PULSE PROPAGATION
M.L. Balistreri et al (University of Twente, NL) discuss laser
pulse propagation, the authors making the following points:
     1) The propagation of ultrafast laser pulses plays an
important role in many aspects of modern optical science. As the
pulses get shorter, their spectral content and peak intensity
increase, giving rise to phenomena such as self-phase modulation,
soliton formation, and other nonlinear effects. With the
appearance of advanced photonic structures, a new dimension has
been added to the manipulation of light propagation, particularly
the strong influence photonic crystals have on the propagation of
pulses. The geometry of the structures leads to intriguing
phenomena such as the creation of gap solitons or the occurrence
of extremely short tunneling times. In addition to the academic
interest, pulse propagation is important in telecommunication
applications, where the above-mentioned effects can be either
detrimental or beneficial for information transport via fiber
networks.
     2) The authors demonstrate that the propagation of a
femtosecond laser pulse inside a photonic structure can be
directly visualized and tracked as it propagates using a time-
resolved photon scanning tunneling microscope. From the time-
dependent and phase-sensitive measurements, both the group
velocity and the phase velocity are unambiguously and
simultaneously determined. The authors suggest this technique
will find applications in the investigation of the local dynamic
behavior of photonic crystals and integrated optical circuits.
-----------
Science 2001 294:1080
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20. CHEMICALLY INDUCED ELECTRONIC EXCITATIONS AT METAL SURFACES
B. Gergen et al (University of California Santa Barbara, US)
discuss electronic excitations at metal surfaces, the authors
making the following points:
     1) Knowledge of the details of energy transfer and
dissipation processes during reactions on metal surfaces is
fundamental to understanding heterogeneous catalysis. Highly
exothermic surface reactions in which energy transfer occurs by
nonadiabatic processes giving rise to excited electronic states
are well known: e.g., gas reactions on alkali metals can give
rise to exoelectrons and chemiluminescence. For low-energy
processes (equal to or less than 0.5 eV), however, electronic
excitations are thought to play a minor role in energy
dissipation, and at present there is no comprehensive theory to
quantitatively predict the partitioning of the interaction energy
of a reactant with a metal surface into the various dissipation
modes.
     2) This problem has been addressed theoretically from
several points of view, each with various ad hoc approximations,
including a perturbation of an electron system by a time-varying
electromagnetic potential from a gas-phase species in transit, an
electrodynamic effect of the polarization fields of a molecular
charge outside a metal, and a secondary Auger electron process.
     3) The authors report they have developed large-area ultra-
thin-film Schottky diode devices that provide direct evidence for
nonadiabatically generated charge carriers during chemisorption
of both atomic and molecular adsorbates on several metal surfaces
with adsorption potentials well below the metal work functions.
The device structure was designed so that electronic excitations
generating electrons with sufficient energy to surmount the
Schottky barrier would be measured as a chemically induced
reverse diode current, a "chemicurrent".
-----------
Science 2001 294:2521
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21. USING NUCLEI TO STORE QUANTUM COMPUTER INFORMATION
L.M. Vandersypen et al (IBM Almaden Research Center, US) discuss
quantum computation, the authors making the following points:
     1) What is known as "Shor's factoring algorithm" involves
the use of a quantum computer to quickly determine the period of
the function f(x) = a^(x)mod(N) (the remainder of a^(x) divided
by N), where (a) is a randomly chosen small number with no
factors in common with (N). From this period, number-theoretic
techniques can be used to factor (N) with high probability.
     2) The number of steps any classical computer requires to
find the prime factors of an L-digit integer (N) increases
exponentially with (L), at least using algorithms known at
present. Factoring large integers is therefore conjectured to be
intractable classically, an observation underlying the security
of widely used cryptographic codes. Quantum computers, however,
could factor integers in only polynomial rather than exponential
time, using Shor's quantum factoring algorithm. Although
important for the study of quantum computers, experimental
demonstration of this algorithm has proved elusive.
     3) The authors report an implementation of the simplest
instance of Shor's algorithm: factorization of N = 15 (whose
prime factors are 3 and 5). The authors use 7 spin-1/2 nuclei in
a molecule as quantum bits, which can be manipulated with room
temperature liquid-state nuclear magnetic resonance techniques.
This method of using nuclei to store quantum information is in
principle scalable to systems containing many quantum bits, but
such scalability is not implied by the present work. The authors
suggest the significance of their work lies in the demonstration
of experimental and theoretical techniques for precise control
and modeling of complex quantum computers. In particular, the
authors state they present a simple and parameter-free but
predictive model of decoherence effects in their system.
-----------
Nature 2001 414:883
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22. ON SOLID-STATE LIGHTING
A. Bergh et al (Optoelectronics Industry Development Assoc., US)
discuss solid-state lighting, the authors making the following
points:
     1) Approximately 20 percent of electricity is used for
lighting. The most widely used sources of artificial illumination
are incandescent and fluorescent lamps, but this is about to
change: solid-state devices promise to replace conventional light
sources, with impressive economic and environmental savings. In
the US, expenditures for lighting may be reduced by $100 billion
over the period 2000-2020. By the year 2020, electricity used for
lighting may be cut by 50 percent, sparing the atmosphere 28
million metric tons of carbon emission annually.
     2) Not only will solid-state lighting lead to energy and
environmental savings, but it will change the way we think about
lighting. Solid-state lighting devices are vibration and shock
resistant, and exceptionally long-lived. They will allow for a
wide variety of lighting, including artificial lighting similar
to natural daylight. Moreover, with appropriate circuitry, the
color and intensity of the lighting can be controlled. Because
solid-state devices can be coupled to light-pipes, light may be
flexibly and efficiently distributed. Solid-state lighting
devices also offer interesting design possibilities: such devices
can be manufactured as flat packages of any shape that can be
placed on floors, walls, ceilings, or even furniture.
     3) Solid-state lighting sources can be made with either
inorganic or organic semiconductors: a) A solid-state lighting
device that uses inorganic semiconductors is a light-emitting
diode (LED). Its essential elements are an electron-carrying (n)
layer and hole-carrying (p) layer. When a forward voltage is
applied to the structure (negative to the (n) layer and positive
to the (p) layer), electrons are injected from the n-layer and
holes from the p-layer. Electrons and holes can radiatively
recombine. emitting a photon whose wavelength and color is
determined by the difference in the energy levels of the
electrons and holes. b) A light-emitting device built with
organic semiconductors is an OLED, and it works very much like an
LED, except that it features an electron-injecting contact
(cathode) instead of the n-layer, and a hole-injecting contact
(anode) instead of the p-layer. LEDs provide point sources for
light, similar to incandescent lamps, while both LEDs and OLEDs
can replace area sources similar to fluorescent lamps.
-----------
Physics Today 2001 December
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23. SOLID-STATE NMR AND SUPRAMOLECULAR SYSTEMS
S.P. Brown and H.W. Spiess (Max Planck Institute for Polymer
Science Mainz, DE) discuss NMR methods for supramolecular
systems, the authors making the following points:
     1) In current polymer science, there is considerable
interest in the design of well-ordered superstructures based on
self-assembly of carefully chosen blocks. Of particular
importance in this context are noncovalent interactions, e.g.,
hydrogen-bonding and aromatic pi-pi interactions. It has been
demonstrated, for example, that linear polymers and reversible
networks are formed from the self-assembly of monomers
incorporating two and three 2-ureido-4-pyrimidone units,
respectively, because of the propensity of these units to
dimerize strongly in a self-complementary array of four
cooperative hydrogen bonds. But such specific interactions are
not a prerequisite for a well-controlled self-assembly: e.g., the
self-assembly in bulk of dendritic building blocks into
spherical, cylindrical, and other supramolecular architectures
occurs as a consequence of both shape and complementarity and the
demixing of aliphatic and aromatic segments.
     2) Despite the presence of considerable order on different
length scales, single crystals suitable for diffraction studies,
and thus full crystal structures, are not available for such
self-assembled supramolecular entities. If the mechanisms
governing self-assembly are to be better understood, analytical
methods capable of probing the structure and dynamics of these
partially ordered systems are essential. In recent years, the
field of solid-state nuclear magnetic resonance (NMR) has enjoyed
rapid technological and methodological development, and advanced
solid-state NMR methods are currently well placed to meet the
challenge of modern polymer chemistry. In particular, with such
methods much insight can be achieved with small amounts (10 to 20
milligrams) of as-synthesized samples.
-----------
Chem Revs. 2001 101:4125
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24. ON PHOTONIC CRYSTALS AND BAND GAPS
John D. Joannopoulos (Massachusetts Institute of Technology, US)
discusses photonic crystals, the author making the following
points:
     1) Photonic crystals have emerged as a potentially powerful
platform for making light do things previously impossible. For
example, optical light could be guided through air rather than
through optical fibers, which would reduce losses. Photonic
devices, from high-speed switches to low-power microlasers, would
be useful ingredients in fiber-optics communications and in
future approaches to high-speed optical computing. The essential
idea is to design periodic structures that affect the behavior of
photons in much same way that crystalline semiconductors affect
the properties of electrons.
     2) Central to this idea is the formation of a photonic "band
gap" -- a range of frequencies for which light is forbidden to
exist within the bulk of the photonic crystal. The presence of a
band gap depends on a particular periodic structure within the
crystal, but whereas the periodic arrangement of atoms occurs
naturally in semiconductors, photonic crystals need to be
fabricated artificially.
     3) The challenge of fabricating photonic band-gap structures
is enormous, since the lattice constant of the photonic crystal
(the size of the periodic unit cell) must be comparable to the
wavelength of the light passing through the crystal. Optical
communications systems, for example, operate in the near-
infrared, which means that the photonic crystal-lattice constant
must have dimensions of approximately a micron. Although this is
some 2000 times larger than the lattice constant of atomic
crystals, it is still over 100 times smaller than the average
diameter of a human hair. At such micron length scales,
controlling the fabrication of intricate structures is far from 
straightforward.
-----------
Nature  2001 414:257
-----------
Related Background:
PHOTONIC CRYSTALS AND OPTOELECTRONICS
The term "photonic crystal" refers in general to a crystal
lattice in which diffraction of electromagnetic radiation occurs
with visible light. An example of such a lattice is a material
consisting of a periodic array of drilled microscopic holes.
... ... Eli Yablonovitch (University of California Los Angeles,
US) discusses photonic crystals, the author making the following
points:
     1) The microelectronics and information revolution is based
on the elaborate control of electric currents achieved with
semiconductors such as silicon. That control depends on a
phenomenon called the "band gap", a range of energies in which
electrons are blocked from traveling through the semiconductor.
     2) Researchers have produced materials with a "photonic band
gap" -- a range of wavelengths of light blocked by the material
-- by structuring the materials in carefully designed patterns
(e.g. arrays of holes) at the nanoscopic size scale. These
photonic crystals function as "semiconductors for light" and
promise innumerable technological applications.
     3) Many researchers greeted the idea of a photonic band gap
with skepticism and disinterest when it was first proposed in the
late 1980s, but today photonic crystals are rapidly becoming big
business, with applications such as high-capacity optical
filters, color filters photonic integrated circuits that would
manipulate light in addition to electric currents, nanoscopic
lasers, light-emitting diodes, and radio-frequency antennas and
reflectors. Integrated circuits that combine conventional
electronics and photonic crystals would represent the ultimate
limit of optoelectronic miniaturization.
-----------
Scientific American 2001 December
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25. IN FOCUS: READING THE MIND OF A FISH
"When two cichlids approach one another to contest control over
some resource, and they are equally matched in all respects, each
is stimulated simultaneously to attack and to flee from the
other. The external signs suggest they experience a conflict
between aggression and fear. As they start their approach, they
seem highly aggressive: The mouth is clenched shut, and the gill
covers, or opercles, are flared out from the head. The median
fins are spread, but the spines of the dorsal fin may be laid
back. The colors are intensified and are rich in contrast. As
they come closer together, signs of fear become steadily more
detectable. They slow their head-on approach. Once in close
proximity, each turns off, presenting its side to the opponent so
the two fish become aligned, side by side, sometimes head next to
head and sometimes head to tail. Now all the fins are fully
spread. Predictably, each fish opens its mouth wide.
Concurrently, it passes deep sideways undulations down its body
while braking with its pectoral fins to resist the forward force;
this behavior is called tail beating, and it may be done in a
forceful snap-whip fashion. The result is an imposing display and
one that washes the opponent with a hefty flow of water that may
even be perceived as sound. All of this behavior indicates
conflict. Each fish has positioned itself so that it is prepared
either to flee or to attack."
-----------
George W. Barlow: _The Cichlid Fishes_
(Perseus Publishing, Cambridge MA 2000, p.97)
http://www.amazon.com/exec/obidos/ASIN/0738205281/scienceweek

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In the text, the affiliation following the names of authors in
sources with more than one author is the affiliation of the lead
author.

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