ScienceWeek

ScienceWeek - April 26, 2002 Vol. 6 Number 17

An Online Research Digest Published Weekly Since 1997


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This vain presumption of understanding everything can have no
other basis than never understanding anything. For anyone who
had experienced just once the perfect understanding of one
single thing, and had truly tasted how knowledge is
accomplished, would recognize that infinity of other truths of
which he understands nothing.
-- Galileo Galilei (1564-1642)

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Section 1

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Contents of this Issue (Full reports in Section 2):

[(*) = includes background reports from ScienceWeek] [Subheads
under each report (e.g., 2a) provide supplementary material from
other archives (links available only in Web Edition of SW)]

Basic Sciences:

1. Functional Genomics and the Mouse Genome (*) 

2. "Rolling" of Biological Cells 

3. Insulin Signaling (*) 

4. Accumulation of Mutations in Asexual Populations 

5. Subsurface Life in Deep-Sea Sediments 

6. Water at Protein Surfaces 

7. On Overlap Decay of Identical Propagating Wave Fields 

8. Surface Science: On Adsorption
8a. Adsorption 

9. Structure and Properties of Carbon Nanotubes 

10. Early Earth: Carbonaceous Meteorites as a Source of Sugars
10a. Meteorites and Their Properites 

11. History of Chemistry: On Svante Arrhenius (1859-1927) 

12. Cosmology: The 20th Century Revolution (*)
12a. The Cosmic Microwave Background Radiation

Praxis:

13. Sleep Deprivation and Performance of Physicians (*) 

14. Engineering Ligand-Receptor Pairs in the Study of Gene
Function 

15. Embryonic Stem Cell Therapy in the Treatment of Parkinson's
Disease 

16. Effects of Iron Deficiency and Iron Excess (*) 

17. Long-Term Effects of Heavy Marijuana Use
17a. On Marijuana 

18. On the Beta-Amyloids of Alzheimer's Disease 

19. Carbon and the Structure of Fullerenes
19a. Discovering the Fullerenes: Nobel Lecture by R.E. Smalley

20. Nanoscale Encapsulation 

21. On Intense Laser Fields 

22  Lithography and Fabrication of Aligned Microstructures 

23. On First Principles Alloy Theory 

24. On Quantum Cryptography 

Miscellany:

25. In Focus: Microbes and the Origins of Species 

26. ScienceWeek Notices and Subscription Information

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Section 2

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1. ON FUNCTIONAL GENOMICS AND THE MOUSE GENOME

L.C. Schalkwyk et al (Max Planck Institute of Molecular Genetics
Berlin, DE) discuss functional genomics, the authors making the
following points:

1) The human genome sequence will provide us with a wealth of
information, including a catalogue of human genes. However,
neither the sequence by itself nor in vitro studies (including
expression profiles and proteomics) give direct access to
previously unknown functions. Mutations, whether spontaneous or
induced, are the geneticist's most important tool to link
phenotypic effects to underlying genes and functional
interactions. Positional cloning of human disease genes and
mouse mutations have given us access to completely novel genes,
but in general, these have been rare, drastic, single-locus
traits. Many more gene functions will become accessible through
positional cloning of the genes behind more common but more
subtle variation in many quantitative traits.

2) Genes and their respective functions have been mainly
conserved among mammals, so that model organisms can be used for
studies of gene function. For many reasons, the mouse is the
most suitable model organism for functional studies. First, mice
are small mammals with a short generation time and relatively
low maintenance costs; second, a large number of different
inbred strains exist that differ with respect to particular
phenotypical aspects; and third, spontaneous and induced
mutagenesis has produced a fund of thousands of mutations, and
this provides us with a huge body of different entry points to
understand in molecular terms what causes observed phenotypic
differences.

3) Of particular importance with respect to identifying
causative genes is availability of a clone-based physical map of
the mouse genome that is as complete as possible. Once genetic
mapping has located candidate regions on the map, clones within
these intervals can be used for the identification of candidate
genes for mouse genomic sequencing and functional studies that
include the generation of transgenic animals. The authors
present an advance global physical map of the mouse genome.

Genome Research 2001 11:2142

Related background:

MOLECULAR BIOLOGY: ON THE RAT AS A MODEL SYSTEM IN FUNCTIONAL
GENOMICS

In a few years, the complete sequence of nucleotide bases in the
human genome will be determined. But that is only the first
phase of the new human biology of the 21st century: after
specification of the complete sequence will come years of
arduous work identifying specific new genes and relating the
proteins encoded by these genes to specific sets of events in
health and disease. This second phase of genome research, the
"functional genomics era", will be carried out, for the most
part, on animals, using animal models to formulate hypotheses
concerning the role played by various parts of the human genome
in human biology. The basis for the use of animal models in this
undertaking is the strong apparent similarity of the genomes and
physiology of certain mammalian species to the human genome and
human physiology. The mouse, a small mammal easily maintained
and easily bred, is currently the favorite animal model used in
mammalian genetics research, but there are a number of
candidates for future functional genomics, and researchers, as
always, will need to make important strategic decisions
concerning the focus of their laboratory work. Intrinsic to the
use of an animal model in functional genomics is the complete
sequencing of the genome of that animal.

... ... Howard J. Jacob (Medical College of Wisconsin, US)
presents a review of the role the rat will play in annotating
the human genome in the functional genomics era. The author
makes the following points:

1) The author points out that the laboratory rat, _Rattus
norvegicus_, was the first mammalian species domesticated for
scientific research, with work dating back to before 1850. From
this beginning, the rat has become the most widely studied
experimental animal model for biomedical research. Since 1966,
nearly 500,000 research articles reporting the use of rats have
been published, with most of these articles focused on
evaluating the biology and/or pathobiology of the rat. In
contrast to its central role in the study of behavior,
biochemistry, neurobiology, physiology, and pharmacology, the
rat has lagged far behind the mouse as a genetic model organism.

2) The author points out that although research on rat genetics
and mouse genetics historically had a parallel beginning, the
mouse soon became the model of choice for mammalian geneticists,
whereas the rat became the model of choice for physiologists,
nutritionists, and other biomedical researchers. Geneticists
preferred the mouse because of its smaller size, which
simplified housing requirements, and the availability of many
coat-color and other mutants exhibiting Mendelian patterns of
inheritance. In contrast, physiologists and other biomedical
researchers favored the rat because its larger size facilitated
experimental interventions, and over time a large number of rat
models were used to develop disease models by selective breeding
that fixed natural disease *alleles in particular strains or
colonies.

3) The author concludes: "The rat offers many advantages for
identification of gene functions that relate to common human
diseases, because of the existing body of knowledge of
physiological mechanisms, the availability of models that mimic
these diseases, the ease of breeding, and the ability to
generate new and better models that match subsets of patients at
both the *phenotypic and genomic levels... Once genes and their
functions are identified in rats, pathophysiologic mechanisms
can be elucidated, and human genetic counterparts can be more
easily identified." Genome Research 1999 9:1013

Notes:

... ... *alleles: An allele is one of two or more forms of a
given gene that control a particular characteristic, with the
alternative forms occupying corresponding loci on homologous
chromosomes.

... ... *phenotypic and genomic levels: In general, the term
"phenotype" refers to the total appearance of an organism as
determined by the interaction during development between its
genetic constitution (genotype) and the environment.

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2. ON ROLLING OF BIOLOGICAL CELLS

"Lymphocytes" are white blood cells (leukocytes) formed
throughout the body, and generally comprise approximately 25
percent of the total number of leukocytes. The so-called B- and
T-lymphocytes are intimately involved in both the adaptive and
innate immune response of vertebrates.

The lymphatic system is a complex network for the distribution
of lymph fluid (which is similar to blood plasma -- blood
without red cells). Lymph is collected by drainage from the
tissues throughout the body, flows in the lymphatic vessels
through the lymph nodes, and is eventually added to the venous
blood circulation.

In general, the term "stem cells" refers to undifferentiated
cells that upon differentiation can give rise to various
specialized cell lines such as blood cells, skin cells, nerve
cells, etc.

In general, the term "neutrophil" refers to any cell or tissue
with no special affinity for acid or basic dyes, but in
immunology the term specifically refers to certain cells of the
immune system, a certain type of mature leukocyte (white blood
cell) that normally comprises about half of the leukocytes that
circulate in the system. They are immune system phagocytes,
i.e., they "eat" bacteria and foreign debris.

... ... M.R. King and D.A. Hammer (University of Pennsylvania,
US) discuss rolling of cells, the authors making the following
points:

1) The adhesion of cells to surfaces in the microvasculature is
important in a number of phenomena, including the inflammatory
response, lymphocyte homing to lymphatic tissues, and stem cell
homing. A key step in these adhesive interactions is "rolling",
in which the adhesion of cells to surfaces slows motion but does
not stop the motion of a cell under hydrodynamic flow. Rolling
is caused by the coordinated formation and breakage of receptor-
ligand bonds at the front and back of the cell, respectively.
Initial adhesive contact in inflammation is mediated by the
selectin family of molecules: P- and E-selectin, expressed on
the surface of endothelial cells, and L-selectin, which is found
at the tips of leukocyte microvilli and their corresponding
ligands. Rolling leads to firm adhesion and the accumulation of
neutrophils at inflammatory sites, the binding of monocytes to
atherosclerotic sites, and the homing of stem cells to bone
marrow.

2) Recent evidence suggests that the accumulation of leukocytes
at inflammatory sites is a collective phenomenon, and it has
been demonstrated that neutrophil-neutrophil interactions cause
an enhancement in the accumulation of leukocytes rolling on
P-selectin in vitro. Transient tether formation between a
rolling cell and one freely suspended in the fluid, mediated by
L- selectin, causes free-flowing cells to be captured by the
surface and roll adhesively. This capture mechanism tends to
align the rolling neutrophils into linear "trains" and is
characterized by a time-dependent acceleration of neutrophil
accumulation on P- selectin.

Proc. Nat. Acad. Sci. 2001 98:14919

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3. ON INSULIN SIGNALING

A.R. Saltiel and C.R. Kahn (University of Michigan, US) discuss
insulin signaling, the authors making the following points:

1) Despite periods of feeding and fasting, plasma glucose
remains in a narrow range between 4 and 7 millimolar in normal
individuals. This tight control is governed by the balance
between glucose absorption from the intestine, production by the
liver, and uptake and metabolism by peripheral tissues. Insulin
increases glucose uptake in muscle and fat, and inhibits liver
(hepatic) glucose production, thus serving as the primary
regulator of blood glucose concentration. Insulin also
stimulates cell growth and differentiation, and promotes the
storage of substrates in fat, liver, and muscle by stimulating
lipogenesis, glycogen and protein synthesis, and inhibiting
lipolysis, glycogenolysis, and protein breakdown. Insulin
resistance or deficiency results in profound dysregulation of
these processes, and produces elevations in fasting and
postprandial glucose and lipid levels.

The epidemic of type 2 diabetes and impaired glucose tolerance
is one of the main causes of morbidity and mortality worldwide.
In both disorders, tissues such as muscle, fat, and liver become
less responsive or resistant to insulin. This state is also
linked to other common health problems, such as obesity,
polycystic ovarian disease, hyperlipidemia, hypertension, and
atherosclerosis. The pathophysiology of insulin resistance
involves a complex network of signaling pathways, activated by
the insulin receptor, which regulates intermediate metabolism
and its organization in cells. However, recent studies have
demonstrated that numerous other hormones and signaling events
attenuate insulin action, and are important in type 2 diabetes.

Nature 2001 414:799

Related Background:

PHYSIOLOGY: ON INSULIN

The term "hormone" was first used in 1902 by William Bayliss
(1860-1924) and Ernest Starling (1866-1927) to describe the
action of secretin, a hormone produced by the mammalian
*duodenum and which stimulates the secretion of pancreatic
juice. Based more on physiological effects than on chemical
structure, subsequent use of the term "hormone" led to the
definition of hormones as signal molecules, products of
glandular cells, with the signal molecules secreted into the
internal milieu, most frequently into the blood. Acting on
target cells, these chemical messengers coordinate activities of
different parts of the body. Target cells, in turn, respond
according to their degree of differentiation, age, and
functional and nutritional status, the target cells integrating
many hormonal and neuronal regulatory stimuli. The target cell
"receptor" is a specific chemical structure required for target
cells to receive and recognize a hormone messenger. In general,
hormone receptors transduce the external chemical signals
provided by hormones and are responsible for the initiation of
the first cellular responses to hormones, this first response
usually involving a cascade of specific biochemical reactions
inside the cell.

The disease *diabetes mellitus has a long history, but it was
only in 1869 that Paul Langerhans (1847-1888) identified a new
type of cell in the pancreas, cells apparently glandular in
character, and histological groups of these cells came to be
called "islets of Langerhans". In 1889, von Mering and Minkowski
demonstrated that diabetes mellitus, characterized in its most
evident form by permanent high blood sugar (hyperglycemia) and
glucose in the urine (glycosuria; glucosuria) could be induced
experimentally in the dog by total removal of the pancreas. This
demonstrated the essential role of the pancreas in the
regulation of glucose balance (glucose homeostasis). The hormone
responsible for this action was called "insulin", and was
finally isolated from the pancreas in 1922 by Frederick Banting
(1891-1941) and Charles Best (1899-1978) [*Note #1]. This
discovery had an enormous impact in physiology, biochemistry,
and medicine. The discovery had an extremely beneficial effect
on the prognosis and therapy of insulin-dependent diabetes,
allowing a specific replacement treatment for endogenous insulin
deficiency, which if untreated is potentially fatal. The arrival
of the insulin era was also of major importance in protein
chemistry. Insulin was one of the first proteins to be
crystallized (Abel 1926), and its primary structure was the
first to be elucidated (Sanger 1953). Partial synthesis was
accomplished between 1964 and 1966, and total synthesis was
completed in 1974. Human insulin, available commercially, is
currently prepared by a modification of pork insulin or by a
biosynthetic process involving genetic engineering.

The insulin molecule consists of two polypeptide chains
connected by two disulfide bridges, with a third disulfide
bridge linking parts of one chain. This two-chain structure has
evidently been present throughout evolution, but major
variations in the amino acid sequences are observed between
species. Various mammalian insulins usually have similar
potencies in all mammals, including humans; fish insulin has
considerable potency in mammals. It is evidently the
3-dimensional structure of insulin, and not the primary sequence
of amino acid residues, which is responsible for its potency
across different species: variations in amino acid sequence are
still potent, provided the specific 3- dimensional structure is
maintained.

Insulin apparently exerts its glucose-lowering effects by
stimulating glucose uptake in tissues such as skeletal muscle,
suppressing fatty acid release from fat (adipose) tissue, and
inhibiting production of glucose by the liver. Muscle, liver,
and fat, therefore, are widely viewed as the principal insulin-
sensitive tissues in the body. The brain, in contrast, has
historically been considered insulin-insensitive because its
ability to use glucose does not require insulin. Because of
this, the idea that insulin participates in the central nervous
system control of food intake and body weight was received with
skepticism when it was first proposed more than 20 years ago.
Since then, however, support for this hypothesis has steadily
accumulated, including the demonstration that insulin is
transported across the *blood-brain barrier, that it is
effective in suppressing food intake when given directly into
the brain, and that insulin receptors are concentrated in brain
areas involved in energy homeostasis.

... ... J.C. Bruening et al (10 authors at 3 installations, DE
US) present new evidence concerning insulin signaling in the
brain, the authors making the following points:

1) The authors point out that insulin receptors and insulin
signaling proteins are widely distributed throughout the central
nervous system. To study the physiological role of insulin
signaling in the brain, the authors created mice with a neuron-
specific disruption of the insulin receptor gene (no-insulin-
receptor knockout mice = NIRKO mice). Inactivation of the
insulin receptor had no effect on brain development or neuronal
survival.

2) The authors report that female NIRKO mice showed increased
food intake, and both male and female mice developed
diet-sensitive obesity with increases in body fat and plasma
*leptin levels, mild insulin resistance, elevated plasma insulin
levels, and *hypertriglyceridemia. NIRKO mice also exhibited
impaired *spermatogenesis and *ovarian follicle maturation
because of *hypothalamic dysregulation of *luteinizing hormone.
The authors conclude: "Thus, insulin receptor signaling in the
central nervous system plays an important role in regulation of
energy disposal, fuel metabolism, and reproduction."

... ... In a commentary on the this work, Michael W. Schwartz
(University of Washington Seattle, US) states: "Bruening and
colleagues provide important evidence to support [the hypothesis
that insulin participates in the central nervous system control
of food intake and body weight]... The stage is now set for
studies to determine if impaired central nervous system
signaling by insulin and leptin contribute to the pathogenesis
of two common metabolic diseases, obesity and *type 2 diabetes."

Science 22 Sep 00 289:2066,2122

Notes:

... ... *duodenum: The duodenum is the first segment of the
intestine attached to the stomach.

... ... *diabetes mellitus: A metabolic disease in which
carbohydrate utilization is reduced and that of lipid and
protein enhanced, the disease caused by an absolute or relative
deficiency of the hormone insulin.

At left: Frederick Banting (1891-1941)

... ... *Note #1: For their isolation of insulin, Banting and
MacLeod received the Nobel Prize for Physiology and Medicine in
1923. The human story has been told many times in books and in
film. Briefly, Banting was a scientifically minded physician
without a laboratory who came to the established physiologist
MacLeod in the early part of 1921 to beg laboratory space to
work on the isolation of insulin. MacLeod tried to discourage
Banting, saying he would not succeed, but finally MacLeod agreed
to give Banting some laboratory space and an assistant, Charles
Best. MacLeod then went off to Europe and did not return until
September 1921, only to find Banting and Best had indeed
isolated insulin. Banting and Best wanted to present their work
to the December 1921 meeting of the American Physiological
Society, but they were unable to do this because neither of them
were members of the Society. MacLeod, who was a member, attached
his name to the paper, and the paper was published under the
three names in 1922. When the Nobel Prize was awarded to Banting
and MacLeod, Banting was furious and at first refused to accept
the prize. He finally did accept, but he immediately transferred
half the prize money to Charles Best. MacLeod then gave half
_his_ prize money to James Collip, an assistant who had helped
in the later purification of insulin.

... ... *blood-brain barrier: A selective mechanism opposing the
passage of most ions and large molecular-weight compounds from
the blood to brain tissue, the mechanism operating in a
continuous layer of endothelial cells connected by tight
junctions between cells. (Endothelial cells are flat cells
forming a layer lining blood vessels, lymphatic vessels, the
heart, etc.)

... ... *leptin: First isolated in 1994 by Y. Zhang et al,
leptin is a hormone secreted by fat cells (adipocytes), the
hormone circulating in blood at levels proportionate to fat
stores and acting in the brain to reduce food intake and body
weight. Insulin deficiency in type 1 diabetes does not cause
weight gain, but rather is associated with severe and
progressive weight loss. In contrast, leptin deficiency is
associated with severe obesity syndrome.

... ... *hypertriglyceridemia: Abnormally high concentrations of
triglycerides in blood.

... ... *spermatogenesis: In general, the entire process that
results in the production of sperm cells.

... ... *ovarian follicle: One of the spherical cell
aggregations in the ovary, the aggregation containing an egg
cell (ovum).

... ... *hypothalamic: The hypothalamus is a deep brain
structure with various clusters of nerve cells controlling
several important homeostatic functions such as temperature
regulation and food intake, and in addition the sex drive,
aggressive emotions, psychosomatic effects, etc. The
hypothalamus essentially integrates the activity of the
autonomic nervous system, and it acts as an intermediary between
the endocrine (hormone) system and the nervous system, with
various hypothalamic neuron types secreting hormones themselves.

... ... *luteinizing hormone: A hormone produced by the
pituitary gland. Luteinizing hormone has a complex interaction
spectrum, but in general, this hormone stimulates secretion of
testosterone in males, and stimulates secretion of estrogen in
females. The hormone is important both in the production of
sperm and in the production of egg cells.

... ... *type 2 diabetes: Adult-onset diabetes mellitus.
Juvenile-onset diabetes mellitus is type 1 diabetes mellitus.
There are two major forms of diabetes: diabetes mellitus and
diabetes insipidus. When the term "diabetes" is used alone, the
usual referent is diabetes mellitus, which in turn has two
types: juvenile-onset (type 1) and adult-onset (type 2). The
various forms and types of diabetes differ in important ways in
both the physiology and biochemistry of the disease processes.

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4. ON THE ACCUMULATION OF MUTATIONS IN ASEXUAL POPULATIONS

A. Colato and J.F. Fontanari (University of Sao Paulo, BR)
discuss mutations in asexual populations, the authors making the
following points:

In an asexual population, random loss of all individuals with
the fewest mutations, i.e., those in the least-loaded class, is
irreversible because the chance of occurrence of back mutations
is negligible in very long gene sequences. As the vast majority
of new mutations are probably slightly deleterious, and the
offspring have at least as many mutations as their parents,
asexual populations are at risk of degenerating, in the sense
that their mean fitness is continually decreasing. This process
of irreversible accumulation of deleterious mutations, known as
"Müller's ratchet", has been advanced as a possible reason for
the evolution of recombination, since sexual reproduction can
recreate individuals that have fewer mutations than their
parents. Despite recent results questioning the relevance of
Müller's ratchet to the evolution of sex, the fitness loss in
asexual populations, mainly RNA viruses, is already a
well-established experimental fact. Moreover, the understanding
of the operation of the ratchet is of great importance, since
this process may be involved in the degeneration of the Y
chromosome and mitochondria.

From a theoretical standpoint, one important issue concerns the
rate with which the ratchet clicks, usually defined as the
inverse of the mean time between successive losses of the
least-loaded classes. Since the pioneering work of Haigh,
studies of the ratchet rate have been carried out in the
framework of the classical Wright-Fisher model of an asexually
reproducing population of fixed size. Although many
approximations to the ratchet rate, valid for different ranges
of the control parameters of the model, have been proposed, a
reliable general expression for this quantity remains to be
obtained.

Phys. Rev. Lett. 2001 87:238102

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5. 0N SUBSURFACE LIFE IN DEEP-SEA SEDIMENTS

S. D'Hondt et al (University of Rhode Island, US) discuss biota
of deep-sea sediments, the authors making the following points:

 During the past 15 years, studies of Ocean Drilling Program
(ODP) cores have consistently identified abundant prokaryotes in
deeply buried oceanic sediments. Microorganisms have been
recovered from depths as great as 800 meters below the seafloor,
and the potential for in situ activity of sub-seafloor
microorganisms has been demonstrated by geochemical and
radiotracer experiments on sediments from a range of burial
depths. In recent contamination-tracer experiments, most of the
microorganisms reported from ODP cores were inherent to the
drilled sediments.

The number and mass of prokaryotes in sub-seafloor sediments
have been estimated by extrapolation from direct counts of
sedimentary microorganisms at a small number of ODP sites. On
the basis of that extrapolation, these prokaryotes constitute
one-tenth to one-third of Earth's biomass. In situ metabolic
activity by at least some of these prokaryotes is spectacularly
demonstrated by hydrates of methane produced in deep-sea
sediments. These hydrates contain 4 to 8 times the amount of
carbon in Earth's surface biomass and terrestrial soils
combined. Pore water chemical studies and recent microbiological
discoveries suggest that, on an ongoing basis, the methane
produced in deep-sea sediments may be primarily destroyed by
sulfate reducing activity of microorganisms in overlying
sediments.

In general, the metabolic rates of sub-seafloor life are orders
of magnitude lower than those of life on Earth's surface. Most
microorganisms in sub-seafloor sediments are either inactive or
adapted for extraordinarily low metabolic activity.

Science 2002 295:2067

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6. ON WATER AT PROTEIN SURFACES 

S.K. Pal et al (California Institute of Technology, US) discuss
water at protein surfaces, the authors making the following
points:

1) Water is essential for the stability and function of
biological macromolecules, proteins, and DNA. Hydration plays a
major role in the assembly of the structure of a protein and in
protein dynamics. For example, water molecules around
hydrophobic and hydrophilic sites are important for the
understanding of the activity of enzyme proteins, and are part
of the process of recognition by other proteins and non-protein
molecules. The water molecules that make up the hydration shell
in the immediate vicinity of the surface are particularly
relevant for function, and in that sense are termed "biological
water". The nature of this shell "layer" has been the focus of
numerous studies both theoretical and experimental, but there is
no generalized picture of the dynamics at the local molecular
level.

2) X-ray crystallography, neutron diffraction, and molecular
dynamics studies have demonstrated that at protein surfaces
water molecules are site-selective and can be restricted in
their motion, even existing in some cases in the form of
clusters.. For example, neutron diffraction experiments followed
by molecular dynamics simulations on carboxymyoglobin reveal
that among the 89 water molecules associated with the protein, 4
water molecules remain bound during the entire length of the
molecular dynamics simulation, whereas the rest undergo
continuous exchange between bound and free states on a variety
of time scales. On the basis of dielectric measurements and NMR
studies, it has been demonstrated that the relaxation times for
water associated with biomolecules occur on various time scales,
from a few tens of picoseconds to the nanosecond time regime.

3) The authors report direct study with femtosecond resolution
of the dynamics of hydration at the surface of the enzyme
protein Subtilisin Carlsberg, whose single tryptophan residue
was used as an intrinsic biological fluorescent probe. The
authors report their results demonstrate that hydration at the
surface is a dynamical process with two general types of
trajectories, those that result from weak interactions with the
selected surface site, giving rise to bulk-type solvation (with
a solvation time of approximately 1 picosecond), and those that
have a stronger interaction, enough to define a rigid water
structure, with a solvation time of 38 picoseconds, much slower
than that of the bulk. At a distance of approximately 7
angstroms from the surface, essentially all trajectories are
bulk-type.

Proc. Nat. Acad. Sci. 2002 99:1763

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7. ON PROPAGATING WAVE FIELDS IN CHAOTIC SYSTEMS

N.R. Cerutti and S. Tomsovic (Washington State University, US)
discuss waves in  chaotic systems, the authors making the
following points:

1) There are many physical systems in which the quantum
evolution of a particle or wave field interacts with a
time-varying, complicated, and essentially unknowable medium.
Well-known examples include acoustic waves propagating long
distances through the sound channel of the ocean, starlight
passing through our atmosphere, and electrons diffusing through
a metal. In a similar vein, wave/quantum evolution problems
whose underlying ray/classical analogs are simple chaotic
systems may possess parameters that are tunable or time-varying
as well. In all of these systems, understanding the effects of
system changes on dynamics is of great interest.

2) The overlap between time-evolved perturbed and unperturbed
states has in recent years been studied in many contexts and
guises, and such overlap has been suggested as a measure of the
stability of quantum motion. Overlap has been identified with
the Loschmidt echo and studied in the context of polarization
echoes in nuclear magnetic resonance, where a crossover between
Gaussian and exponential behavior of the overlap was observed.
In quantum computing, it is equivalent to the "fidelity", which
measures the loss of phase coherence, and fidelity has been
shown to have different functional decay forms in the chaotic
and integrable limits.

3) Over the past 10 years, it has been demonstrated that
semiclassical theories of wave mechanics based on
rays/trajectories are capable of quantitatively reproducing
evolving wave fields in chaotic dynamical systems for
significant propagation times during which the chaos can become
extremely well developed.

4) The authors report a theoretical investigation of the problem
of the overlap decay of two initially identical wave fields
propagating in slightly different simple chaotic systems, the
study using semiclassical dynamics to derive the functional
dependence of the decay process on time, Planck's constant, and
perturbation strength. The authors report the evolution of the
wave field is considerably more stable than the exponential
instability of chaotic trajectories seems to suggest.

Phys. Rev. Lett. 2002 88:054103

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8. SURFACE SCIENCE: ON ADSORPTION

Daniel J. Auerbach (IBM Almaden, US) discusses adsorption, the
author making the following points:

1) Adsorption --- the process whereby an atom or molecule in the
gas or liquid phase loses some of its initial energy and becomes
bound on a surface --- is a prerequisite for all chemical
reactions in which reactants first adsorb on a solid surface and
then interact to form products. In many-body systems, energy can
be lost through a variety of loss channels, and understanding
the relative importance of these channels in the adsorption
process is thus key to understanding such chemical reactions.

2) As an incident particle approaches a solid surface, it
interacts with the electrons of the solid, and by perturbing
these electrons, it also generates interactions with the ion
cores in the lattice. Two broad classes of energy-dissipation
channels arise from these interactions: excitation of lattice
vibrations (phonons) and electronic excitations, which include
particle emission, photon emission, and the excitation of
electron-hole pairs.

3) At high interaction energies, there is abundant evidence for
electronic excitation. For some channels, particles or photons
can be observed directly and their participation in the
adsorption process established unambiguously. As early as 1905,
Thomson observed the emission of negative particles following
adsorption of various gases on an alkali metal surface. Many
examples of emission of electrons and ions (exo-emission) and of
photons (chemiluminescence) in highly exothermic reactions at
surfaces are now known.

4) At lower energies, the importance of electronic excitations
in adsorption tends to decrease for several reasons. Processes
like exoemission and chemiluminescence cannot occur below a
certain energy threshold. Thus, only phonons and electron-hole
pairs are available to dissipate energy. Furthermore, the
electrons in the solid have more time to adjust smoothly to the
perturbation of a slow incoming particle. The system therefore
tends to evolve adiabatically, with energy dissipated to phonons
rather than to nonadiabatic electronic excitations.

Science 2001 294:2488

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9. STRUCTURE AND PROPERTIES OF CARBON NANOTUBES

H.F. Bettinger et al (Rice University, US) discuss carbon
nanotubes, the authors making the following points:

1) Multiwall carbon nanotubes, a new tubular form of carbon,
were discovered in 1991 by S. Iijima. Carbon nanotubes are
comprised of a rolled graphite sheet ("graphene") and closed by
fullerene-like caps. Depending on the way the graphene is
rolled, different chiralities are possible, and are commonly
distinguished by their chiral vector (n,m). The (n,n) tubes are
called "armchair" and the (n.0) tubes are called "zigzag"
nanotubes. A simple analysis imposing appropriate boundary
conditions on the graphene band structure predicts that the
armchair tubes are metallic (i.e., the band gap is zero due to
band crossing), whereas the zigzag tubes are either semimetals
or semiconductors, depending on the value of (n). The
computations of the band structures using density functional
theory (plane-wave pseudopotential local density approximation)
indicate that these simple rules need to be refined, at least
for narrow zigzag tubes. It was found by these calculations that
the rehybridization of the carbon states due to the strong
curvature of small tubes introduces low-lying conduction band
states into the band gap of insulating tubes.

2) Whereas Iijima's multiwall carbon nanotubes consist of at
least 2 concentric tubes, single wall carbon nanotubes are
produced by laser vaporization of a metal-graphite (Co, Ni)
target. These single-wall nanotubes are comprised of a single
rolled graphene sheet, but have a tendency to form "ropes",
i.e., bundles of single-wall nanotubes. The tubes produced by
the laser-oven technique have very uniform diameters of
approximately 1.38 +- 0.02 nanometers, according to x-ray
diffraction, and an intertube distance of 0.315 nanometers in
the ropes, similar to that in crystalline C(sub60). It has been
concluded that the ropes are made up of (10,10) armchair
single-wall nanotubes.

J. Am. Chem. Soc. 2001 123:12849

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10. EARLY EARTH: CARBONACEOUS METEORITES AS A SOURCE OF SUGARS

"Stony" meteorites (aerolites) are meteorites formed solely of
rock-forming silicates, and chondrites are a type of stony
meteorite consisting of an agglomeration of millimeter-sized
globules (chondrules) that are thought to be unchanged since the
original condensation out of the nebula from which the Sun and
Solar System formed. A "carbonaceous chondrite" is a chondritic
meteorite that contains a relatively large amount of carbon,
with a resultant dark appearance. The "Murchison meteorite" is a
carbonaceous chondrite that fell in 1969 near Murchison,
Australia. The Murray meteorite, which fell to Earth in Kentucky
1950, is similar to the Murchison meteorite in its organic
content

G. Cooper et al (NASA Ames Research Center, US) discuss
meteorites and early Earth, the authors making the following
points:

1) The much studied Murchison meteorite is generally uses as the
standard reference for organic compounds in extraterrestrial
material. Amino acids and other organic compounds important in
contemporary biochemistry are thought to have been delivered to
the early Earth by asteroids and comets, and such compounds may
have played a role in the origin of life on Earth.

2) Polyhydroxylated compounds (polyols) such as sugars, sugar
alcohols, and sugar acids are vital to all known lifeforms ---
they are components of nucleic acids, cell membranes, and also
act as energy sources. But there has hitherto been no conclusive
evidence for the existence of polyols in meteorites, leaving a
gap in our understanding of the origins of biologically
important organic compounds on Earth.

3) The authors report that a variety of polyols are present in,
and indigenous to, the Murchison and Murray meteorites in
amounts comparable to amino acids. Analysis of water extracts
indicate that extraterrestrial processes, including photolysis
and formaldehyde chemistry, could account for the observed
compounds. The authors conclude that polyols were present on the
early Earth and therefore at least available for incorporation
into the first forms of life.

Nature 2001 414:879

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11. HISTORY OF CHEMISTRY: ON SVANTE ARRHENIUS (1859-1927)

At left: Svante Arrhenius (1859-1927)

The Arrhenius theory of electrolytes, introduced in 1887 by
Arrhenius when he was a graduate student, proposed that acids
are substances that dissociate in water to yield electrically
charged atoms or molecules, called "ions", one of which is a
hydrogen ion (H+), and that bases ionize in water to yield
hydroxide ions (OH-. It is now known that the hydrogen ion
cannot exist alone in water solution, but that instead it exists
in a combined state with a water molecule as the hydronium ion.
Although these ideas of Arrhenius were scorned by his teachers,
the Arrhenius theory of electrolytes came to form the basis of
20th century solution chemistry.

J. Van Houten (Saint Michael's College Colchester, US) discusses
the Nobel laureate chemist Svante Arrhenius, the author making
the following points:

1) Svante Arrhenius won the Nobel Prize in 1903 for his
electrolytic theory of dissociation, which extended van't Hoff's
ideas about the nature of molecules in solution into the realm
of aqueous salts, acids, and bases. However, Arrhenius's ionic
dissociation theory was initially considered controversial, and
his 1884 doctoral dissertation, "Investigations on the Galvanic
Conductivity of Electrolytes", received the lowest possible
grade, "not without merit", at the University of Uppsala.

2) Arrhenius was the first Swede to win a Nobel Prize in any
field. Although he was recognized for his electrolytic theory of
dissociation, his name is most familiar to modern chemistry
students because of its association with a definition of acids
and bases, and through the equation that relates reaction rate
constants to activation energies and temperature. Both
contributions of Arrhenius, the electrolytic theory and the
activation energy concept, have been important in the
development of modern concepts of chemical dynamics.

3) Arrhenius studied with Jacobus van't Hoff (1852-1911) (Nobel
Prize 1901) and with Wilhelm Ostwald (1853-1932) (Nobel Prize
1909). Arrhenius was actually considered for the physics as well
as for the chemistry prize in 1903. In 1905, The Royal Swedish
Academy of Sciences established a Nobel Institute for Physical
Chemistry with Arrhenius as its first chief. Arrhenius went on
to become chairman of the Nobel Committee for Physics of the
Royal Swedish Academy of Sciences, and in that capacity gave the
presentation speech for Albert Einstein in 1921 and for Niels
Bohr in 1922.

J. Chem. Ed. 2002 79:21

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12. COSMOLOGY: THE 20TH CENTURY REVOLUTION

William G. Unruh (University of British Columbia, CA) discusses
cosmology in the 20th century, the author making the following
points:

1) In the early years of the 20th century, Ernest Rutherford
(1871-1937), the great experimental physicist at Cambridge, was
reputed to have thundered, "If anyone in my laboratory begins to
speak of the Universe, I tell him it is time to leave." Since
its beginnings, cosmology, the study of the Universe as a whole,
has been characterized by a mixture of seemingly outrageous
speculation and subsequent verification.

2) Einstein founded his 1915 theory of gravity on one
unexplained experimental fact --- that all objects fall in
exactly the same way in a gravitational field --- and a demand
for consistency with his theory of special relativity. Through
an unparalleled intellectual tour de force, he created a theory
in which the flow of time from place to place and the creation
and destruction of space depend on matter. Shortly thereafter,
Alexandr Friedman and Georges Lemaitre each pointed out that
this theory implied that the Universe is dynamic and had a
beginning. Einstein found this conclusion sufficiently repugnant
to try to change his theory. Only a few years later, Edwin
Hubble demonstrated that faint smudges of light in the telescope
were distant galaxies whose distance from us increases faster
the further they are from us, just as had been predicted. Space
really does grow, and time has a beginning.

3) The second half of the 20th century witnessed a dazzling
increase in the ability of astronomers to make observations of
the remotest regions of the Universe. The new technologies were
manifold. Radio communications gave us radio astronomy and the
detection of the cosmic background radiation from the earliest
days of the Universe. Consumer electronics provided the
charge-coupled device camera, which enabled the imaging of
galaxies hundreds of times dimmer than the night sky itself.
High precision spectroscopy allowed the detection of the small
changes in the motion of distant stars due to planets orbiting
those stars. Cosmology has thus changed from a field dominated
by speculation and unconstrained theoretical extrapolation to an
observational science, in which theories can be abandoned
because of disagreement with observation rather than merely
because of the death of their proponents.

Science 2002 295:1649

Related background:

COSMOLOGY: OPEN, CLOSED, OR FLAT UNIVERSE?

Marc Kamionkowski (Columbia University, US) reviews current
research in cosmology, making the following points: 1)
Determination of the geometry of the universe has been a central
goal of cosmology ever since Hubble discovered its expansion 75
years ago. 2) The central question is whether the universe is a
multi-dimensional equivalent of a 2-dimensional surface
("flat"), a sphere ("closed"), or a saddle ("open"). The
geometry, in the context of current theory and observations,
determines whether the universe will expand forever or
eventually collapse. 3) Until now, most astronomers have pursued
the geometry by attempting to measure the mass density of the
universe. According to general relativity, if the density is
equal to, larger than, or smaller than a critical density fixed
by the expansion rate, then the universe is flat, open, or
closed, respectively. 4) Another possibility is to look directly
at the predicted observational effects of a curved (open or
closed) universe versus a flat universe, and in particular at
the angular power spectrum of the cosmic microwave background.
The authors suggest that in the near future a new generation of
experiments will provide substantial advances in these
observations, enabling more definitive statements about the
geometry of the universe, and that these results will in turn
provide clues to the new particle physics required to understand
the inflation phase following the Big Bang origin of the
universe.

Science 1998 280:1397

Related Background:

COSMIC BACKGROUND RADIATION AND COSMOLOGICAL MODELS

The central problem of cosmology is to provide a self-
consistent view of the past, present, and future of the Universe
that takes into account not only concepts and observations in
astrophysics but also concepts and observations in all of
physics, particularly those in particle physics and quantum
physics. Thus, a cosmological model is a conceptual edifice
built with the bricks of fundamental physics, and as physics
changes, and observations change, so do the acceptable models.
Can there be a "final theory" in cosmology? Probably not until
there is a "final physics", a physics in which all new
observations are without surprises. We are certainly not there
yet; in fact, the objective is so distant, there is perhaps not
even a glimmer of a shadow in the murky mist. But as the
astrophysicist Edwin Hubble said, "The search will continue. The
urge is older than history. It is not satisfied and it will not
be oppressed."

Contemporary cosmology distinguishes two kinds of matter,
"ordinary matter" and "dark matter". In general, a baryon is a
nuclear particle (e.g., a proton) built from 3 quarks
(fundamental particles that combine to make up protons,
neutrons, and mesons), and so-called "ordinary matter" is
baryonic. In this context, the term "dark matter" refers to
material whose presence can be inferred from its effects on the
motions of stars and galaxies, but which cannot be seen directly
because it emits little or no radiation. It is believed that as
much as 90 percent of the mass in the Universe may exist as some
form or dark matter, although the proposed percentage of dark
matter varies widely with different cosmological models.

The major current cosmological models propose a "Big Bang", an
initial explosive origin of the Universe at a time zero. The
inflationary model, first proposed by Alan Guth in 1980,
proposes that quantum fluctuations in the time period 10^(-35)
to 10^(-32) seconds after time zero were quickly amplified into
large density variations during the "inflationary" 10^(50)
expansion of the universe in that time frame, and that these
density variations eventually led to the formation of galaxies
and clusters of galaxies.

What is known as the "cosmic microwave background radiation" was
discovered accidentally in 1964, when A.A. Penzias and R.
Wilson, measuring noise that might interfere with satellite
communications, noted a mysterious signal that was soon
interpreted to be the microwave background radiation originating
in the Big Bang. In 1978, Penzias and Wilson received the Nobel
Prize in Physics for this discovery. The cosmic microwave
background is black-body radiation (the emission radiation of a
perfect absorber of radiation) at a present temperature of 2.73
degrees Kelvin, and has an almost equal intensity in all
directions in space. The deviations from isotropic intensity,
however, are of extreme importance in theoretical cosmology.

Central to current cosmological considerations are the
distinctions between the geometries of a "flat" (uncurved;
infinite in both extent and lifetime), "closed" (spherical;
finite in both extent and lifetime), and "open" (*hyperbolic;
infinite and expanding forever) Universe. An important quantity
is the Omega parameter, defined as the ratio of the density of
matter (or energy) in the Universe to the theoretical density
required for flatness. An Omega with a value of greater than 1
implies a closed Universe; a value less than 1 implies an open
Universe; a value equal to 1 implies a flat Universe. The
problem for the past 60 years has thus been to obtain an
estimate of the mass density of the Universe from observations.
The current standard conception is that the geometry of the
Universe is flat.

... ... Craig J. Hogan (University of Washington Seattle, US)
presents a commentary on current research in cosmology, the
author making the following points:

1) Recent measurements of temperature variation in the cosmic
microwave background reveal distinctive patterns in these
fluctuations, patterns which depend on the details and
composition of the Universe, and cosmologists are beginning to
interpret these patterns through detailed statistical studies.
The results are in accord with the expectations of inflation --
a nearly "flat" Universe, which can be described as a small
piece of an enormous *hypersphere -- and in accord with
independent estimates of various quantities such as the density
of dark matter.

2) Nevertheless, there are several unexpected and possibly
important discrepancies. The sharpest and most interesting
discrepancy is the estimate of the density of ordinary
(baryonic) matter in the Universe: the new data suggest that the
mean number of neutrons and protons per unit volume is greater
than was thought.

3) The author concludes: "Exploration of this discrepancy might
lead to something really new -- perhaps a simple
reinterpretation of data on abundances, or perhaps a new
ingredient not yet included in the standard cosmological model."

Nature 2000 408:47

Notes:

... ... *hypersphere: If one considers a circle (2-dimensional),
a sphere (3-dimensional), the term "hypersphere" refers to the
subsequent members of the series, where the number of dimensions
is >= 4. A hypersphere is thus defined as the set of n-tuples of
points [x(sub1), x(sub2), ..., x(subn)] such that x(sub1)^(2) +
x(sub2)^(2) + ... + x(subn)^(2) = R^(2) where R is the radius of
the hypersphere.

Related Background:

COSMOLOGY: EXPECTATIONS IN THE NEXT CENTURY OF RESEARCH

Cosmology is one of the grand sciences, a domain of research
whose results have enormous intellectual consequences, at least
for people who care about what they are and where they are.
Martin Rees (Cambridge University, UK) presents an essay on the
near-future research expectations of cosmologists, the author
making the following points:

1) Astronomers still do not know what the Universe is made of.
Observable radiation-emitting objects -- such as stars,
*quasars, and galaxies -- apparently constitute only a small
fraction of the matter in the Universe. The vast bulk of matter
is dark and unaccounted for, and most cosmologists believe this
dark matter is composed of weakly interacting particles left
over from the *Big Bang. But dark matter could be something more
exotic. "Whatever the case, it is clear that galaxies, stars and
planets are a mere afterthought in a Cosmos dominated by quite
different stuff." The author suggests that intensive searches
for dark matter, mainly via sensitive underground experiments
designed to detect elusive subatomic particles, will continue in
the coming decade, and that within the next decade both the
amount and nature of dark matter will be clarified.

2) The author suggests that research in the near-future is also
likely to focus on the evolution of the large-scale structure of
the Universe. The current view is that ever since the Big Bang,
gravity has been amplifying inhomogeneities, building up
structures and enhancing temperature contrasts -- "a
prerequisite for the emergence of the complexity that lies
around us now and of which we're a part." The author suggests
that astronomers are now learning more about the 10 billion year
process of Cosmic evolution by creating virtual universes on
computers, and that in the coming years researchers will be able
to simulate the history of the Universe with ever improving
realism and then compare the results with astronomical
observations.

3) The author suggests that the great mystery for cosmologists
is the series of events that occurred less than 1 millisecond
after the Big Bang, when the Universe was extraordinarily small,
hot, and dense. "The laws of physics with which we are familiar
offer little firm guidance for explaining what happened during
this critical period." To solve this problem, it will necessary
to improve and refine current observations in order to
understand the characteristics of the Universe when it was only
one second old: its expansion rate, the size of its density
fluctuations, and its proportions of ordinary atoms, dark
matter, and radiation.

4) The author suggests the following Cosmic timeline for the
evolution of the Universe from the Big Bang to the present:

... ... a) 10^(-43) seconds after the Big Bang: the *Quantum
Gravity Era.

... ... b) 10^(-36) seconds after the Big Bang: Probable *Era of
Inflation.

... ... c) 10^(-5) seconds after the Big Bang: Formation of
protons and neutrons from *quarks.

... ... d) 3 minutes after the Big Bang: Synthesis of atomic
nuclei.

... ... e) 300,000 years after the Big Bang: First atoms form.

... ... f) 1 billion years after the Big Bang: Appearance of
first stars, galaxies, and quasars.

... ... g) 10 to 15 billion years after the Big Bang: Appearance
of modern galaxies.

5) The author concludes: "How did a hot amorphous fireball
evolve, over 10 to 15 billion years, into our complex Cosmos of
galaxies, stars, and planets? How did atoms assemble -- here on
Earth and perhaps on other worlds -- into living beings
intricate enough to ponder their own origins? These questions
are a challenge for the new millennium. Answering them may well
be an unending quest."

Scientific American December 1999

Notes:

... ... *quasars: (quasi-stellar objects). Extremely luminous
sources radiating energy over the entire spectrum from x-rays to
radio waves, and which are apparently the oldest and most
distant objects in the universe. They are believed to involve
massive black holes.

... ... *Big Bang: The Big Bang theory is the general
cosmological model that proposes that all matter and radiation
in the universe originated in an explosion at a finite time in
the past.

... ... *Quantum Gravity Era: Quantum field theory is the
mathematical fusion of quantum mechanics with special relativity
theory, and the term "quantum gravity" refers to the fusion of
quantum mechanics with general relativity theory. The essential
basis for these fusions is the so-called "equivalence
principle", which identifies the mass involved in the
gravitational force equation with the inertial mass in the
equation that relates any force to the product of inertial mass
and acceleration. The "quantum gravity era" is the time-frame
during which both quantum effects and gravity determined the
behavior of particles.

... ... *Era of Inflation: The inflationary model, first
proposed by Alan Guth in 1980, proposes that quantum
fluctuations in the time period 10^(-35) to 10^(-32) seconds
after time zero were quickly amplified into large density
variations during the "inflationary" 10^(50) expansion of the
universe in that time frame.

... ... *quarks: A quark is a hypothetical fundamental particle,
having charges whose magnitudes are one-third or two-thirds of
the electron charge, and from which the elementary particles may
in theory be constructed.

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13. SLEEP DEPRIVATION AND PERFORMANCE OF PHYSICIANS

M.B. Weinger and S. Ancoli-Israel (University of California San
Diego, US) discuss sleep deprivation and cllinical performance,
the authors making the following points:

1) Sleep deprivation can affect clinical performance and may be
an important factor in patient safety. The complexity of modern
health care makes the conduct of high-quality prospective
controlled research on the effect of physician work and sleep
schedules extremely difficult. Naturalistic studies, which are
likely to be most generalizable, are especially difficult due to
the tremendous variability in physician and practice attributes
(e.g., work schedule, workload, case mix). Most studies of
recurrent partial sleep deprivation have suggested that sleeping
only 5 to 6 hours a night can lead to impairment.. These
decrements in performance accumulate with continued partial
sleep deprivation, as may be seen in individuals with chronic
insomnia or in physicians working regularly recurrent call or
night shifts. In the early morning hours, after nearly 24 hours
without sleep (e.g., at the end of a difficult night on call),
psychomotor performance can be impaired to an extent equivalent
to or greater than is currently acceptable for alcohol
intoxication.

2) The authors conclude that the current body of evidence
supports the assertion that physicians' sleep schedules are
important factors in determining their performance in specific
clinical situations. In particular, patient care may be
compromised if a fatigued, sleep-deprived clinician is allowed
to operate, administer an anesthetic, manage a medical crisis,
or deal with an unusual or cognitively demanding clinical
presentation. The effects of acute sleep deprivation on clinical
performance will depend on many salient contextual factors,
including chronic sleep deprivation, time of day (circadian
effects), clinical experience, task demands, and clinical
workload. Individual work and sleep schedules, under specific
but hard to anticipate circumstances, will be an important
factor affecting the occurrence of medical error.

3) The authors suggest that physicians must recognize that it is
neither unprofessional nor weak to admit sleepiness or fatigue
when on the job, and that physicians must make efforts to
mitigate the potential consequences to patient care.

J. Am. Med. Assoc. 2002 287:955

Related background:

IS US HEALTH CARE REALLY THE BEST IN THE WORLD?

In general, the health of a population is "public health", and
public health is for the most part a consequence of both culture
and national policy. The US is one of the major developed
countries on the planet, with what is probably the most
developed scientific enterprise, but is this intense scientific
effort correlated with a comparable high level of health care
for the US population? For the most part, the answer is
apparently no.

... ... Barbara Starfield (Johns Hopkins University, US)
presents a commentary on current assessments of US health care,
the author making the following points:

Information concerning deficiencies of US medical care has been
accumulating, although the high cost of the US health care is
apparently tolerated under the assumption that better health
results from more expensive care. The facts are as follows:

1) More than 40 million people in the US have no health
insurance.

2) 20% to 30% of patients in the US receive contraindicated care.

3) An estimated 44,000 to 98,000 people in the US die each year
as a result of medical errors.

4) According to several studies, the US population does not have
anywhere near the best health in the world. Of 13 countries in a
recent comparison, the US ranks an average of 12th (second from
the bottom) for 16 available health indicators. Countries in
order of average ranking on the health indicators (with first as
best) are Japan, Sweden, Canada, France, Australia, Spain,
Finland, the Netherlands, the UK, Denmark, Belgium, the US, and
Germany. On separate indicators, the rankings of the US are as
follows:

... ... Low birth-weight percentages: 13th (last in ranking)

... ... Neonatal mortality and infant mortality overall: 13th

... ... Postneonatal mortality: 11th

... ... Life expectancy at 1 year for females: 11th

... ... Life expectancy at 1 year for males: 12th

... ... Life expectancy at 15 years: females 10th; males 12th

... ... Life expectancy at 40 years: females 10th; males 9th

... ... Life expectancy at 65 years: females 7th; males 7th

... ... Life expectancy at 80 years: females 3rd; males 3rd

... ... Age-adjusted mortality: 10th

5) The poor performance of the US was recently confirmed by the
World Health Organization, which used different indicators, the
WHO report ranking the US as 15th among 25 industrialized
countries. Although common explanations for the poor performance
of the US in these rankings blame the "bad behavior" of
Americans (e.g., smoking, drinking, violence, etc.), the data
comparing such behavior to the behavior of the people in other
countries indicates otherwise. Concerning the long-existing poor
ranking of the US with regard to infant mortality, this
low-ranking is not the result of the high percentages of low
birth-weight and infant mortality among the US black population,
since the international ranking hardly changes when data for the
white population only are used.

6) The US health care system may contribute to poor health
through its adverse effects. For example, US estimates of the
combined effect of errors and adverse effects that occur because
of *iatrogenic damage include:

... ... 12,000 deaths per year from unnecessary surgery.

... ... 7000 deaths per year from medication errors in hospitals.

... ... 20,000 deaths per year from other errors in hospitals.

... ... 80,000 deaths per year from *nosocomial infections in
hospitals.

... ... 106,000 deaths per year from non-error adverse effects
of medications.

These total to 225,000 deaths per year from iatrogenic causes,
so that iatrogenic cause is the 3rd leading cause of death in
the US, after deaths from heart disease and cancer. 7) The
author concludes: "Recognition of the harmful effects of health
care interventions, and the likely possibility that they account
for a substantial proportion of the excess deaths in the US
compared with other comparably industrialized nations, sheds new
light on imperatives for research and health policy. Alternative
explanations for these realities deserve intensive exploration."

J. Am. Med. Assoc. 2000 284:483

Notes:

... ... *iatrogenic: In general, this denotes any result
produced by surgery or other treatment. In this context, and in
the usual usage, the term is used for a result that is unwanted
and injurious to the patient (e.g., an infection due to
contaminated surgical instruments).

... ... *nosocomial infections: In general, a nosocomial
infection is any infection acquired by a patient as a result of
entrance into a hospital. It is estimated that some 15 to 20
percent of all hospital workers carry the bacterial pathogen
Staphylococcus aureus on the skin of their hands, and that 60 to
70 percent of all hospital workers carry S. aureus in their
nostrils.

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14. ENGINEERING LIGAND-RECEPTOR PAIRS IN THE STUDY OF GENE
FUNCTION

D.F. Doyle et al (Georgia Institute of Technology, US) discuss
the elucidation of gene function, the authors making the
following points:

1) Completion of genome sequencing projects has placed renewed
emphasis on detailed understanding of how protein networks
function within cells. These networks are composed of
interdependent and often redundant components that combine to
form a complex system, and this complexity poses severe
challenges to exploring the function of newly discovered genes.
To reduce cellular complexity to a level that can be addressed
experimentally, there is a need for simplifying approaches that
can allow the cellular roles of individual proteins to be
determined. One general strategy is to use genetic "knockouts"
(i.e., turn the gene expression off). An alternate "chemical
genetic" strategy is to manipulate protein activities by using
small molecules derived from natural sources, combinatorial
libraries, or design. It has recently been demonstrated that
genetic knockouts can produce different phenotypes relative to
those produced by inhibiting the intact protein, suggesting that
chemical genetics may provide a finer level of detail about
protein function and regulation than can be achieved by genetic
means alone.

2) Nuclear hormone receptors are a superfamily of ligand
inducible transcription factors that activate gene expression in
response to binding of small molecule ligands. These receptors
contain a DNA-binding domain composed of two zinc modules and a
ligand-binding domain that is predominantly alpha-helical. The
ligand-binding and DNA-binding domains are modular, and their
ability to function independently offers important advantages
for engineering the control of gene expression, since the
ligand-binding domain can activate transcription when grafted
onto an exogenous DNA binding domain. Thus many different
chimeric DNA- and ligand-binding domains can be produced and
used to direct ligand-inducible regulation to different genes.

3) The authors demonstrate that nuclear hormone receptors can be
engineered through mutagenesis to create orthogonal
ligand-receptor pairs to control transcription. The authors
suggest their results also demonstrate the general principle
that inactive compounds synthesized during drug discovery can be
combined with mutant proteins to rapidly create new tools for
controlling cellular processes.

J. Am. Chem. Soc. 2001 123:11367

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15. ON EMBRYONIC STEM CELL THERAPY IN THE TREATMENT OF
PARKINSON'S DISEASE

Curt R. Freed (University of Colorado, US) discusses embryonic
stem cell therapy, the author making the following points:

1) Human embryonic stem cells come from preimplantation embryos,
most of which are generated at in vitro fertilization clinics.
Within days after fertilization, the embryo consists of a hollow
sphere, the blastocyst, which contains a cluster of a few
hundred identical cells called the "inner cell mass" that can
eventually develop into a fetus. When removed from the
blastocyst, these cells can be propagated indefinitely in
specialized media. When the media are changed to allow
differentiation, cells continue to divide and aggregate, forming
"embroid" bodies. Although these cell clusters lack the
organization of an embryo, they contain all tissue types,
including skin, muscle, bone, and neurons. Because embryonic
stem cells can become any cell in the body, there is hope that
they will lead to treatment  for diseases like diabetes,
Parkinson's disease, Alzheimer's disease, and heart failure. The
problem is controlling cell growth and differentiation. If large
numbers of embryonic stem cells are transplanted into an organ
like the brain, they grow into every cell type and form
tumor-like masses called teratomas. eventually killing their
host. The problem is thus to restrict embryonic stem cells to
produce useful cells without overgrowing.

2) Bjorklund et al (2002) have transplanted small numbers of
partially differentiated mouse embryonic stem cells from embroid
bodies into a rat model of Parkinson's disease and have
demonstrated that at least some of the cells become the dopamine
neurons that are needed to reverse the Parkinson condition. The
authors suggest that the brain environment may encourage
survival of cells appropriate for treating the disease while
controlling the tendency to form a tumor mass. The results were
far from perfect: Of 25 rats receiving transplants of 1000 to
2000 cells, 56 percent of animals showed surviving grafts
containing dopamine neurons, whereas 20 percent had lethal
teratomas, and 24 percent had no cells survive. Although these
proportions are not promising for a treatment for humans with
Parkinson's disease, the results illustrate the principle that
relatively undifferentiated cells can develop into neurons
appropriate for a specific brain region without invariably
leading to uncontrolled cell growth.

Proc Nat. Acad. Sci. 2002 99:1755,2344

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16. ON THE EFFECTS OF IRON DEFICIENCY AND IRON EXCESS

P.B. Walter et al (University of California Berkeley, US)
discuss iron deficiency, the authors making the following points:

1) Iron deficiency is the most common nutritional deficiency
worldwide, affecting approximately 2 billion people, mostly
women and children. In the US, an estimated 9 million people are
iron deficient. Iron deficiency is a significant public health
concern associated with an increased risk of poor pregnancy
outcomes and impaired cognitive development in young children.
Pregnant women in developing countries are commonly given daily
supplements containing 120 milligrams of iron to prevent and
correct gestational iron deficiency. This dose of iron, which is
10 times the normal daily dietary iron intake, can cause
gastrointestinal side effects.

2) The authors have already reported that equivalent doses of
daily high-iron supplements in rats (i.e., 10 x normal intake,
8000 micrograms iron per day) results in an abnormal
accumulation of intestinal mucosal and hepatic non-heme iron and
significant increases in lipid peroxidation. The authors
unexpectedly observed that iron-deficient rats also had markedly
increased lipid peroxidation, suggesting that both iron
deficiency and iron excess promote oxidative stress.

3) The increased oxidative stress observed in both iron
deficiency and excess may involve mitochondrial dysfunction, as
has been observed in aging and associated degenerative diseases.
Mitochondria use 90 percent of inspired oxygen, produce a
significant amount of cellular superoxide, and accumulate iron
for heme and iron-sulfur cluster formation. Studies of severe
iron overload modeling hemochromatosis have reported increased
hepatic lipid peroxidation, nuclear DNA damage, and
mitochondrial dysfunction. The severe iron overload of
mitochondria has been found to induce mitochondrial DNA damage,
and such damage correlates with the mitochondrial dysfunction
associated with oxidant stress and aging.

4) The authors now report that both inadequate and excessive
iron (10 x nutritional need) cause significant mitochondrial
malfunction. Although excess iron has been known to cause
oxidative damage, the observation of oxidant-induced damage to
mitochondria from iron deficiency has been unrecognized
previously. In summary, the authors suggest that untreated iron
deficiency, as well as excessive iron supplementation, are
deleterious, emphasizing the importance of maintaining optimal
iron intake.

Proc. Nat. Acad. Sci. 2002 99:2264

Related Background:

IRON METABOLISM

G. Nicolas et al (Cochin Institute of Molecular Genetics, FR)
discuss iron metabolism. Iron is an essential element required
for growth and survival of almost every organism. In mammals,
the iron balance is primarily regulated at the level of duodenal
absorption of dietary iron. Following absorption, ferric iron is
loaded into apotransferrin in the circulation and transported to
the tissues, including erythroid precursors, where it is taken
up by transferrin receptor-mediated endocytosis.
Reticuloendothelial macrophages play a major role in the
recycling of iron via the degradation of hemoglobin of senescent
erythrocytes, whereas hepatocytes contain most of the iron
stores of the organism in the form of ferritin polymers. During
the past 5 years, a body of information concerning the proteins
involved in iron absorption and in the regulation of iron
homeostasis has resulted from the study of inherited defects
(both in humans and in mice) that lead to distinct iron
disorders. In the case of iron deficiency, the
pathophysiological consequences of identified gene defects are
well understood, because they usually result in loss of function
of proteins directly involved in the pathway of iron absorption.
In contrast, several abnormalities associated with genetic iron
overload have led to identification of various proteins whose
functional role in the control of iron homeostasis remains only
poorly clarified. The authors report evidence that the liver
protein hepcidin acts as one of the signaling molecules
regulating both intestinal iron absorption and iron storage in
macrophages.

Proc. Nat. Acad. Sci. 2001 98:8780

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17. LONG-TERM EFFECTS OF HEAVY MARIJUANA USE

N. Solowij et al (University of New South Wales, AU) discuss
marijuana use, the authors making the following points:

1) In the current climate of debate about marijuana laws and
interest in marijuana as medicine, one issue remains unresolved:
Does heavy, frequent, or prolonged use of cannabis lead to a
deterioration in cognitive function that persists well beyond
any period of acute intoxication? Is the functioning of the
brain altered in the long term? With over 7 million people using
cannabis weekly or more often in the US alone, and the potential
for increased physician recommendations for select patients to
use cannabis therapeutically, answers to these questions are of
significant public health concern.

2. Past research suggested that gross impairment related to
chronic cannabis use did not occur, but the evidence was
inconclusive with regard to the presence of more specific
deficits. Recent studies with improved methods have demonstrated
changes in cognition and brain function associated with long
term or frequent use of cannabis. Specific impairments of
attention, memory, and executive function have been found in
cannabis users in the unintoxicated state (and in children
exposed to cannabis in utero) in controlled studies using brain
event-related electric potential techniques and
neuropsychological assessments, including complex tasks. In
addition, brain imaging studies of cannabis users have
demonstrated altered function, blood flow, and metabolism in
prefrontal and cerebellar regions.

3) The authors report a multi-site retrospective cross-sectional
neuropsychological study conducted in the US between 1997 and
2000, the study involving 102 near-daily cannabis users (51
long-term users; mean, 23.9 years of use; 51 shorter-term users;
mean, 10.2 years of use) compared with 33 nonuser controls. The
authors report their results confirm that long-term heavy
cannabis users show impairments in memory and attention that
endure beyond the period of intoxication and worsen with
increasing years of regular cannabis use.

J. Am. Med. Assoc. 2002 287:1123

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18. ON THE BETA-AMYLOIDS OF ALZHEIMER'S DISEASE

C. Nicolau et al (Louis Pasteur University Strasbourg, FR)
discuss Alzheimer's disease, the authors making the following
points:

1) Alzheimer's disease is a progressive degenerative disorder of
insidious onset characterized by memory loss, confusion, and a
variety of cognitive disabilities. The major neuropathological
change in the brain of Alzheimer's disease patients is neuronal
death, particularly in regions related to memory and cognition.
One of the major pathological features of the disease is the
abundant presence of amyloid plaques in the brain of the
affected individuals. Intracellular bundles of paired helical
filaments, composed largely of phosphorylated tau protein,
accumulate in large amounts in dying neurons. On the neuron
surfaces, insoluble aggregates of proteinaceous debris, termed
"amyloid", appear in the form of neuritic plaques and vascular
amyloid deposits. The frequency and distribution of the
neurofibrillar tangles and of the neuritic plaques appear to
correlate well with the extent of the cognitive impairment and
other characteristic symptoms of the disease.

2) Amyloid plaques are formed by the beta-amyloid peptide, a 39-
to 43-amino acid-long polypeptide that is mostly coiled and
slightly alpha-helical in its benign soluble form and, on
conformational transition into a mainly beta-sheet secondary
structure, spontaneously aggregates into insoluble deposits.
This peptide is a physiological metabolite of the much larger
"amyloid precursor protein", 695- 770 amino acids long, which
undergoes sequential proteolysis. The peptide may remain in
solution as a random coil or an alpha-helix.

3) The authors report a study in mice whose results indicate
that palmitoylated beta-amyloid peptides, reconstituted in
liposomes-lipid A, are highly immunogenic, eliciting
"therapeutic" antibody titers within 3 months of the first
inoculation and preventing amyloid plaque formation in young
animals or significantly reducing existing plaques in older
transgenic mice. The authors conclude their results suggest a
possible therapeutic and prophylactic role for vaccination with
a chemically modified beta-amyloid peptide fragment
reconstituted in liposomes.

Proc. Nat. Acad. Sci. 2002 99:2332

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19. CARBON AND THE STRUCTURE OF FULLERENES

A.A. Lucas et al (Our Lady of Peace University Brussels, BE)
discuss fullerenes, the authors making the following points:

1) In the periodic table of the elements, carbon is listed as
crystallizing in the hexagonal structure. This structure
consists of planar layers of carbon atoms arranged in honeycomb
lattices called graphene sheets. Within a sheet, 3 of the 4
valence electrons of a carbon atom form 3 strong trigonal bonds
to 3 equidistant neighbors 0.14 nanometers away. The fourth
valence electrons from different carbon atoms interact to form
weak pi-bonds perpendicular to successive sheets that are
loosely piled up  on top of each other every 0.34 nanometers in
an alternating ABAB ... sequence producing a 3-dimensional
hexagonal unit cell. Although there are various other stacking
arrangements, this allotrope, known as "graphite", is the most
stable and most abundant solid form of pure carbon found in
nature. A slightly less stable and vastly less abundant
crystallographic form is diamond, which has a cubic structure in
which each atom is covalently bound to 4 neighbors at the apexes
of a regular tetrahedron.

2) Until approximately 15 years ago, such were the only known
crystalline forms of solid carbon. In 1985, the science of
carbon was unexpectedly enlarged by the discovery of an entirely
new class of structures "fullerenes". The fullerenes first
discovered are spheroidal molecules, and such molecular clusters
are sometimes called "curved graphite" because of their obvious
appearance as curved sheets of graphene, with the typical 3-fold
coordination of each atom in a honeycomb lattice. However,
occasional pentagonal rings occur in the hexagonal network, and
these cause the curvature and eventual closure of the graphene
sheets. Fullerene molecules are in turn able to crystallize in a
variety of 3-dimensional structures.

3) Fullerenes were discovered serendipitously in the soot formed
when a hot carbon vapor (several thousand degrees) cools off and
condenses into clusters in an inert gas atmosphere. The most
abundant and most celebrated such molecule, C(sub60), comprises
60 carbon atoms, all equivalent, regularly arranged in 12
pentagonal and 20 hexagonal rings, in a soccer ball arrangement.
The 1996 Nobel Prize in Chemistry was awarded to R. Curl, H.
Kroto, and R. Smalley, the discoverers of this molecule. Beyond
C(sub60), the next most abundant fullerene in the condensed
carbon vapor is C(sub70). This molecule can be conceived of
being constructed by addition of a ring of 10 atoms at one of
the 5-fold equators of C(sub60). By adding successively (n) such
parallel rings, while maintaining the graphite 3-fold
coordination, one can theoretically produce a series of
cigar-shaped molecules C(sub60+10n). In the limit of large (n),
these are particular members of a subfamily of fullerenes called
"single wall nanotubes". In general, single-wall nanotubes can
be conceived as any such long strip of graphene rolled up into a
seamless cylinder. The latter can be left open or can be capped
by hemifullerenes.

Revs. Mod. Phys. 2002 74:1

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20. ON NANOSCALE ENCAPSULATION

 I.G. Loscertales et al (University of Malaga, ES) discuss
encapsulation, the authors making the following points:

1) Production and control of droplets and particles of
micrometer or even nanometer size with a narrow size
distribution are of interest for many applications in science
and technology. Usually, these particles are formed as either an
aerosol or a hydrosol phase. Aerosols and hydrosols of compound
particles, such that each particle is made of a small amount of
a certain substance surrounded by another substance, are of
particular importance for encapsulation of food additives,
targeted drug delivery, and special material processing, among
other technological fields. In all of these cases, encapsulation
is used to provide compound particles in an appropriate size
range.

2) One of the most widely adopted methods to obtain
micrometer/nanometer capsules is based on emulsion technology.
Two immiscible fluids, one carrying the substance to be
encapsulated and the other fluid carrying the polymer for the
shell, are stirred to form an emulsion. This emulsion is
stabilized by pouring it into a third solution ("double emulsion
 process"), thereby extracting the polymer solvent and
solidifying the polymer as a capsule. Related methods also
incorporate phase separation and similar physical or chemical
phenomena.

3) Other approaches for encapsulation resort to the formation
and control of liquid jets with diameters in the
micrometer/nanometer range. In the electrospray technique, a
conducting liquid is slowly injected through an electrified
capillary tube. When the electric potential between the liquid
and its surroundings rises to a few kilovolts, the meniscus at
the tube exit develops a conical shape, commonly referred to as
the "Taylor cone". A thin microthread of liquid is issued from
the tip of the Taylor cone, which eventually fragments to form a
spray of highly charged droplets. Its most well-known
application has been in mass spectrometry, where it has been
successfully exploited as a way to produce multiply-charged gas
phase ions of huge biomolecules present in the liquid phase.

4) The authors report a method to generate steady coaxial jets
of immiscible liquids with diameters in the range of
micrometer/nanometer size. This compound jet is generated by the
action of electro-hydrodynamic forces with a diameter that
ranges from tens of nanometers to tens of micrometers. The
eventual jet breakup results in an aerosol of monodisperse
compound droplets with the outer liquid surrounding or
encapsulating the inner liquid. The authors report they have
produced monodisperse capsules with diameters varying between
0.15 and 10 microns, depending on the running parameters.

Science 2002 295:1695

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21. ON INTENSE LASER FIELDS

Kaoru Yamanouchi (University of Tokyo, JP) discusses intense
laser fields, the author making the following points:

1) One might think that the problem of completely understanding
the interaction of light with atoms and molecules had already
been solved by sophisticated modern laser spectroscopy and that
nothing remained by the application of this knowledge. However,
the development of ultrashort superintense pulsed lasers has led
to the realization that much remains to be learned about
light-matter interactions.

2) It is well known that ultrashort pulsed lasers allow probing
of molecular processes in real time on the femtosecond time
scale. The latest advances originate not , however, from the
ultrashort temporal width of the laser light but from its
extremely high intensity. The advent of chirped pulse
amplification has greatly increased the output energy of
ultrashort pulsed lasers. Even in university laboratories, laser
light fields as high as 10^(15) watts per square centimeter can
now be generated routinely with a table-top high-power chirped
pulse amplification laser system. This intensity is comparable
in magnitude to the Coulomb field generated by an atomic
nucleus. In large-scale facilities, a laser field intensity of
10^(20) watts per square centimeter could be achieved.

3) At intensities well below approximately 10^(12) watts per
square centimeter (the "perturbative regime") , atoms and
molecules absorb one or multiple photons through a weak
interaction with the light field. At intensities of
approximately 10^(12) to 10^(17) watts per square centimeter
(the "Coulombic regime"), fundamentally different behavior is
observed, and most studies have focused on the characteristic
dynamical behavior of molecules at these intensities. Under
these conditions, the potential surface of a molecule, whose
shape is determined by its electronic configuration, can be
deformed by the intense laser field, and if the shape of the
potential energy surface can be varied in a desired way, the
fate of a molecule could be actively controlled by light.

Science 2002 295:1659

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22. LITHOGRAPHY AND FABRICATION OF ALIGNED MICROSTRUCTURES

J. Tien et al (Johns Hopkins University, US) discuss
microstructure fabrication, the authors making the following
points:

1) Microlithography is generally a binary process, i.e.,
lithography segregates a surface into regions that are exposed
to a modification and regions that are masked from that
modification. In photolithography, irradiation through a mask
that consists of two regions (clear and opaque) defines a map of
exposed and unexposed regions. Similarly, in soft lithography,
placement of an elastomeric stamp that possesses two regions
(recessed and nonrecessed) onto a surface defines regions that
are stamped and those that are not.

2) Fabrication of complex multilevel structures that contain
more than two types of elements is often required for
microelectronic, microfluidic, and microelectromechanical
systems and necessitates multiple applications of lithography in
which each step must be aligned spatially with previous steps.
Alignment of patterning steps in the fabrication of organic,
living, or soft structures has proven to cumbersome for many
reasons: the elastomeric stamps used in soft lithography are
difficult to align over large areas, alignment of biological
materials requires sterile working conditions throughout the
fabrication process, and patterning onto devices that are not
openly accessible (such as a sealed microfluidic device) is
extremely challenging.

3) The authors describe an approach for microfabrication that
encodes the 2-dimensional spatial information of several
photomasks onto a single elastomeric stamp by mapping each
photomask onto distinct heights on the surface of the stamp.
Pressing the stamp against a surface collapses the topography of
the stamp such that each recessed layer contacts the surface in
stepwise sequence. The greater the applied pressure, the larger
the area of the stamp that contacts the surface. After contact
of each new layer with the surface, the authors use techniques
of soft lithography (microcontact printing, microfluidics, and
patterning through membranes) to pattern the surfaces that
contact the stamp and those that do not with inorganic, organic,
or living materials. The authors suggest that microfabrication
through the use of multilevel stamps provides a promising
alternative to conventional lithography for the construction of
multicomponent aligned surfaces, and these strucures may find
use as components of microfluidic devices or biological patterns.

Proc Nat. Acad. Sci. 2002 99:1758

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23. ON FIRST PRINCIPLES ALLOY THEORY

A. van de Walle and G. Ceder (Massachusetts Institute of
Technology, US) discuss alloy theory, the authors making the
following points:

1) New materials having desirable properties are often
discovered by alloying elements (or compounds) that possess some
of the wanted qualities. As both computing power and the
efficiency of computational methods are steadily increasing, it
is becoming possible to investigate new alloys through computer
simulations, before they have even been synthesized. However,
before such a "virtual" material can make its way into the real
world, it must pass the stringent test of thermodynamic
stability. For this reason, the determination of alloy phase
diagrams from first principles is among the most important steps
required to build a "virtual laboratory" where materials could
be designed from first principles without relying on
experimental input.

2) The field of first-principles alloy theory, whose focus is
the calculation of solid-state phase diagrams, has made
substantial progress over the last two decades. As the
thermodynamic most stable form of most solid compounds is
crystalline, alloy theory traditionally investigates the
relative stability of phases characterized by a distinct
ordering of atomic species on a given set of candidate lattices,
allowing for small displacements away from the ideal lattice
sites. Within that conceptual framework, it is now possible to
predict relatively complex solid-state phase diagrams starting
from the basic principles of quantum mechanics and statistical
mechanics. Since no experimental input is required, these ab
initio calculations have been useful for clarifying the phase
diagram of several new materials.

3) The accuracy of calculated phase diagrams is currently
limited by two factors. First, one needs, as a starting point,
the energy of the alloy in various atomic configurations, and
hence one is limited by the accuracy of the quantum-mechanical
calculations used to obtain these energies. Typically, methods
based on density functional theory, such as the local-density
approximation or the generalized gradient approximation are
used. A second shortcoming arises from the fact that in order to
reduce computational requirements, the sampling of the partition
function to obtain the free energy is only done over a limited
number of degrees of freedom. Typically, these include
substitutional interchanges of atoms but no atomic vibrations.
Attempts to either assess the validity of this approximation or
to devise computationally efficient ways to account for lattice
vibrations are currently the focus of intense research. This
interest is fueled by the observation that phase diagrams
obtained from first principles often incorrectly predict
transition temperatures.

Revs. Mod. Phys. 2002 74:11

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24. ON QUANTUM CRYPTOGRAPHY

N. Gisin et al (University of Geneva, CH) discuss quantum
cryptography, the authors making the following points:

1) Electrodynamics was discovered and formalized in the 19th
century. The 20th century was then profoundly affected by its
applications. A similar adventure may be underway for quantum
mechanics, discovered and formalized during the last century,
Indeed, although the laser and semiconductor are already common,
applications of the most radical predictions of quantum
mechanics have only recently been conceived, and their full
potential remains to be explored by the physicists and engineers
of the 21st century.

2) The most peculiar characteristics of quantum mechanics are
the existence of indivisible quanta and of entangled systems.
Both of these lie at the root of quantum cryptography, which
could very well be the first commercial application of quantum
physics at the single-quantum level. In addition to quantum
mechanics, the 20th century has been marked by two other major
scientific revolution: information theory and relativity. The
status of the latter is well recognized. It is less well known
that the concept of information, currently measured in bits, and
the formalization of relevant probabilities are quite recent,
although they have a tremendous impact on our daily life. It is
fascinating to realize that quantum cryptography lies at the
intersection of quantum mechanics and information theory, and
that, moreover, the tension between quantum mechanics and
relativity --- the famous Einstein-Rosen-Podolsky (EPR) paradox
--- is closely connected to the security of quantum cryptography.

3) The idea of quantum cryptography was first proposed in the
1970s by Stephen Wiesner and in the 1980s by Charles H. Bennett
and Gilles Brassard. However, this idea is so simple that any
first-year student since the infancy of quantum mechanics could
actually have discovered it. Nevertheless, it is only now that
the field is mature enough and information security important
enough that physicists are ready to consider quantum mechanics
not only as a strange theory that produces paradoxes but also as
a tool for new engineering. Apparently, information theory,
classical cryptography, quantum physics, and quantum optics
first had to develop into mature sciences. It is certainly not a
coincidence that quantum cryptography and, more generally,
quantum information were developed by a community including many
computer scientists and more mathematically oriented young
physicists: broader interests than traditional physics were
needed.

Revs. Mod. Phys. 2002 74:145

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25. IN FOCUS: MICROBES AND THE ORIGINS OF SPECIES

At left: Lynn Margulis

"The language of evolutionary change is neither mathematics nor
computer-generated morphology. Certainly it is not statistics.
Rather, natural history, ecology, genetics, and metabolism must
be supplemented with accurate knowledge of microbes. Microbial
physiology, ecology, and protistology are essential to
understand the evolutionary process. The behavior of microbes
within their own populations and in their interactions with
others determined life's winding, expanding evolutionary course.
The living subvisible world ultimately underlies the behavior,
development, ecology, and evolution of the much larger world of
which we are a part and with which we co-evolved. While some may
feel belittled by this perspective of evolution punctuated  and
driven forward by microbial mergers, we believe, echoing Darwin,
that there is grandeur, too, in this view of life. Numberless
forms and variation come not just gradually and at random, but
suddenly and forcefully, by the co-opting of strangers, the
involvement and infolding of others --- viral, bacterial, and
eukaryotic --- into ever more complex and miscegenous genomes.
The acquisition of the reproducing other, of the microbe and its
genome, is no mere sideshow. Attraction, merger, fusion,
incorporation, cohabitation, recombination --- both permanent
and cyclical --- and other forbidden couplings, are the main
sources of Darwin's missing variation. Sensitivity, co-optation,
merger, acquisition, fusion, accommodation, perseverance, and
other capabilities of the microbes are not all irrelevant to the
evolutionary process. Far from it. Indeed, as Wallin said in
1927, 'It is a rather startling proposal that bacteria, the
organisms which are popularly associated with disease, may
represent the fundamental causative factor in the origins of
species.' The incorporation and integration of 'foreign'
genomes, bacterial and other, led to significant, useful
heritable variation. The acquiring of genomes has been central
to the evolutionary processes throughout the long and circuitous
history of life."

L. Margulis and D. Sagan: Acquiring Genomes: A Theory of the
Origins of Species. Basic Books, New York 2002, p.204

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