ScienceWeek

ScienceWeek - June 21, 2002
Vol. 6 Number 25

An Online Research Digest Published Weekly Since 1997

--------------------------------------------------

The trick is to listen to what the experiments tell you
-- and to not be fooled by the myths of authorities.
-- Constantine Spyropoulos (1928-1984)

--------------------------------------------------

=-=-=-=-=-=-=-=-=

Section 1

=-=-=-=-=-=-=-=-=

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

1. Biophysics: On Elastic Interactions of Biological Cells 

2. Neurobiology: On Brain Size 

3. Biochemistry: Nitric Oxide 

4. Biology of Aging: Puzzles and Problems 

5. The New Planetary Biology 

6. On Taxonomy 

7. Molecular Structure Theory and Electron Counting Rules 

8. Quantum Theory: On Bell Inequalities 

9. Astrophysics: On Relativistic Jets 

10. Chemistry: On the Resorcinarenes 

11. Chemistry: On Kenichi Fukui (1918-1998) and Roald Hoffmann

12. On Organic Chemical Synthesis 

13. Electric Circuit Control of DNA Hybridization 

14. On the Etiology and Treatment of Schizophrenia 

15. A Genetic Hypothesis for Schizophrenia Susceptibility 

16. On the Problems of Toxicology 

17. Diabetes and Atherosclerosis 

18. On the Future of Health Insurance in the US 

19. On Electrical Detection of DNA 

20. Sulfuric Acid Deterioration of a 17th Century Warship 

21. On Directed Small-World Networks 

22. On Solid Phase Organic Synthetic Chemistry 

23. On the Dissolution of Cellulose by Ionic Liquids

24. On Light-Powered Molecular Machines 

25. In Focus: On Power-Law Degree Distribution Networks 

26. ScienceWeek Notices and Subscription Information

=-=-=-=-=-=-=-=-=

Section 2

=-=-=-=-=-=-=-=-=

1. BIOPHYSICS: ON ELASTIC INTERACTIONS OF BIOLOGICAL CELLS

U.S. Schwarz and S.A. Safran (Max Planck Institute of Colloids
and Interfaces Potsdam, DE) discuss elastic interactions of
biological cells, the authors making the following points:

1) Biological cells can exert strong physical forces on their
surroundings. One example are fibroblasts, which are
mechanically active cells found in connective tissue. In the
early 1980s, Harris and co-workers found that fibroblasts exert
much more force than needed for locomotion [1]. They suggested
that strong fibroblast traction is needed in order to align the
collagen fibers in the connective tissue. Since cell locomotion
is guided by collagen fibers, this results in a mechanical
interaction of cells. The interplay of fiber alignment and cell
locomotion has been analyzed theoretically in the framework of
coupled transport equations for fiber and cell degrees of
freedom [2]. However, it is well known that cellular behavior is
also affected by purely elastic effects, which were not
considered in these studies. For example, stationary cells
plated on an elastic substrate which is cyclically stretched
reorientate away from the stretching direction [3], and
locomoting cells on a strained elastic substrate reorientate in
the strain direction [4]. Recent experiments show that adhering
cells sense mechanical signals through focal adhesions [5]. In
contrast to chemical diffusion fields, elastic effects are long
ranged and propagate quickly, and they are known to be important
during development, wound healing, inflammation, and metastasis.

2) The authors consider theoretically the possibility of elastic
interaction of cells. The authors focus on static forces, a
situation which should apply to cells with restricted
cytoskeletal regulation or to artificial cells which have a
biomimetic contractile system without any regulation; the
authors suggest the theoretical framework presented for this
case is a prerequisite for understanding the more complicated
cases, e.g., the case of locomoting cells with a regulated
response and dynamic force patterns [4]. In the static case, the
elastic interaction of cells through their strain fields leads
to forces and torques which can change their positions and
orientations. If the cellular configuration can relax to
equilibrium, the final configuration will be a minimum of the
elastic energy. The authors derive the laws for elastic
interactions of cells (which are modeled as anisotropic force
contraction dipoles) and show how they depend on elastic
constants, distance, cellular orientations, geometry, and
boundary conditions.

3) In summary: Biological cells in soft materials can be modeled
as anisotropic force contraction dipoles. The corresponding
elastic interaction potentials are long ranged (approximately
l/r^(3) with distance r) and depend sensitively on elastic
constants, geometry, and cellular orientations. On elastic
substrates, the elastic interaction is similar to that of
electric quadrupoles in two dimensions and for dense systems
leads to aggregation with herringbone order on a cellular scale.
Free and clamped surfaces of samples of finite size introduce
attractive and repulsive corrections, respectively, which vary
on the macroscopic scale. The author's theory predicts cell
reorientation on stretched elastic substrates.

References (abridged):

1. A. K. Harris, P. Wild, and D. Stopak, Science 208, 177
(1980); A.K. Harris, D. Stopak, and P. Wild, Nature (London)
290, 249 (1981).

2. G. F. Oster, J. D. Murray, and A. K. Harris, J. Embryol. Exp.
Morph. 78, 83 (1983); V.H. Barocas and R.T. Tranquillo, J.
Biomech. Eng. 119, 137 (1997).

3. P. C. Dartsch, H. Hammerle, and E. Betz, Acta Anat. 125, 108
(1986); J-.H.-C. Wang and E. S. Grood, Connect. Tissue Res. 41,
29 (2000).

4. C.-M. Lo et al., Biophys. J. 79, 144 (2000).

5. N. Q. Balaban et al., Nature Cell Biol. 3, 466 (2001); D.
Riveline et al., J. Cell Biol. 153, 1175 (2001).

Phys. Rev. Lett. 2002 88:048102

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

2. NEUROBIOLOGY: ON BRAIN SIZE

R.M. Sayfarth and D.L. Cheney (University of Pennsylvania, US)
discuss brain size, the authors making the following points:

1) An intriguing question in neurobiology is: "Why do primates
have such big brains?" Across the animal kingdom, brain size
increases with increasing body size. Despite this common scaling
principle, however, brain size to body weight ratios differ from
one taxonomic group to another (2). In primates, for example,
the brains of apes are generally larger relative to body weight
than the brains of monkeys, whereas the brains of monkeys are
larger than those of prosimians (2). Structural differences are
also apparent. In chimpanzees, a larger proportion of the brain
is devoted to neocortex than in monkeys, who in turn have
proportionately more neocortex than prosimians (3, 4). Within
the neocortex, ape (and especially human) brains have a
particularly enlarged prefrontal cortex, an area known to be
involved in many forms of abstract thought and rule learning (5,
6).

2) Increases in the size of primate brains have come despite the
fact that brain tissue is metabolically very costly. What
selective pressures have overcome these costs? When the question
is applied to humans, answers typically refer to the adaptive
advantages of technology (initially, stone tools) and language.
But monkeys and apes use only rudimentary tools and lack
language entirely, yet their brains are significantly larger
than those of similar-sized mammals. Some other selective
pressures must be at work.

3) Among primates, relative brain size (corrected for body
weight) is greater in species with larger home ranges and
greater in species that are fruit-eating or omnivorous than in
species that eat leaves. Species that feed on fruit may face
special problems in learning and memory because they depend on
widely spaced food that is ephemeral in both space and time. In
contrast to this "ecological" explanation of brain evolution,
others suggest that primate brains have evolved primarily to
deal with social problems. Primates, they argue, live in
relatively large groups where an individual's survival and
reproductive success depends on its ability to manipulate others
within a complex web of kinship and dominance relations. In
recent years this "social intelligence" hypothesis has received
some of empirical support. The purported link between brain size
and ecological or social intelligence is, however, entirely
conjectural. We may assume that memorizing the location of ripe
fruit or remembering the kin relations of ones' opponents demand
considerable brainpower, but this assumption is neither
supported nor refuted by any widely accepted evidence. Perhaps
more important, the "intelligence" of different species is
notoriously difficult to compare. Different species manifest
their intelligence in different ways, making it almost
impossible to find an objective measure of intelligent
performance that can be used across many taxa.

References (abridged):

2. Jerison, H. (1973) The Evolution of the Brain and
Intelligence (Academic, New York).

3. Martin, R. D. (1990) Primate Origins and Evolution: A
Phylogenetic Reconstruction (Princeton Univ. Press, Princeton).

4. Passingham, R. E. (1982) The Human Primate (Freeman, Oxford).

5. Deacon, T. (1992) The Symbolic Species (Norton, New York).

6. Miller, E. (1999) Neuron 22, 15-17.

Proc. Nat. Acad. Sci. 2002 99:4141

Related Background:

ON HUMAN FOSSILS AND HUMAN BRAINS

[Editor's note: Prehistoric peoples ranging back to the dawn of
the human species have left us their bones, and from these bones
(when we can find them) we attempt to construct an image of our
ancestors. It is an enormously difficult and murky undertaking,
and the results perhaps most ambiguous when we try to establish
an idea of the perished brains of human fossils. Skulls are
measured to determine the volume of the brain, endocasts are
made to establish the inner surfaces of the skull and perhaps
the convolutions of the brain once protected by that skull, and
there is much controversy in anthropology concerning
interpretations of data. Here is a commentary by a brain
neuroanatomist on the difficulties of knowing the brains of
ancient peoples, his words nearly 40 years old but still
relevant.]

"The results of our inquiries into the brains of fossil men are
somewhat meager: we cannot deduce any details about their mental
life, whether they believed in God, whether they could speak or
not, or how they felt about the world around them... That the
brain increases in size as we go from the Australopithecinae to
modern man -- or to the Upper Paleolithics, for that matter --
is quite obvious and, of course, gratifying. But the meaning of
the increase is again not quite clear because, as we all know,
brain size as such is a very poor indicator of mental ability.
This has been shown best perhaps by [Karl] Pearson [1857-1936]
(1925) some years ago. In his series, very gifted persons, such
as Leon Gambetta [1838-1832], Anatole France [1844-1924], or
Franz Joseph Gall [1758-1828], had very small brains, of about
1100 grams. Other equally gifted persons had very large brains;
thus [George Gordon] Byron [1788-1824] and Dr. [Samuel] Johnson
[1709-1784] had brains of about 2000 grams. And, of course, some
very ordinary persons had equally large brains. So brain size
was certainly not very important, and the correlation between
brain size and mental capacity was insignificant. But whether
this argument can be extended to an evolutionary series is again
another matter. For one thing, we know far too little about the
bodily proportions of fossil forms. Obviously, the brain stands
in a certain relation to the rest of the body, and this rest is
still largely hidden from us. Brain size as such is none too
meaningful. Moreover, mere size completely leaves out of account
the inner structure of the brain, which may be different in
different forms and which may determine to a great extent what
the brain can do."

Gerhardt von Bonin: _The Evolution of the Human Brain_
(University of Chicago Press, 1963, p.76)

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

3. BIOCHEMISTRY: NITRIC OXIDE

Endothelial cells are flat cells forming a layer lining blood
vessels, lymphatic vessels, the heart, etc., and the term
"relaxing factor" refers to any chemical entity that promotes
the relaxation of muscle fibers. The discovery of an
endothelial-derived relaxing factor by R.F. Furchgott in 1980
initiated studies that ultimately led to the identification of
nitric oxide as an endogenous signaling molecule. In the
classical pathway described by Furchgott, nitric oxide is
synthesized by vascular endothelial cells and the substance then
diffuses into the underlying smooth muscle cells to mediate
vascular relaxation. Although this pathway plays a major role in
vascular control, subsequent work has revealed that
endothelium-dependent relaxation is not the only mode for nitric
oxide to regulate blood flow. In certain vascular beds,
regulation of vessel tone by nitric oxide does not require the
endothelium but instead relies on neuronal activity,
specifically on neurons involved in the synthesis of nitric
oxide. (This is the basis for the action of sildenafil [Viagra].)

P.C. Ford and I.M. Lorkovic (University of California Santa
Barbara, US) discuss nitric oxide, the authors making the
following points:

1) It is now well established that nitric oxide (nitrogen
monoxide; NO) plays fundamental roles in biochemical
processes.(1,2) Early concerns with the biology of NO were
largely focused on the known toxicities of NO and other reactive
nitrogen oxide species as constituents of air pollution,
including cigarette smoke.(3) However, natural physiological
activities are now known to include roles in blood pressure
control, neurotransmission, and immune response. Subsequent
reports have identified a number of disease states involving NO
imbalances,(2,4) and such observations have stimulated extensive
research activity into the chemistry, biology, and pharmacology
of NO. This has led to renewed interest in the solution-phase
reactions of NO, since understanding the fundamental chemistry
may provide new insights regarding the physiological roles of
this "simple" molecule.

2) The principal targets for NO under bioregulatory conditions
are metal centers, primarily iron proteins.(5) The best
characterized example is the ferro-heme enzyme soluble guanylyl
cyclase. Formation of a nitrosyl complex with Fe(II) leads to
labilization of a trans axial (proximal) histidine ligand in the
protein backbone, and the resulting change in the protein
conformation is believed to activate the enzyme for catalytic
formation of the secondary messenger cyclic-guanylyl
monophosphate (cGMP) from guanylyl triphosphate (GTP). The
enzymatic formation of cGMP leads to relaxation of smooth muscle
tissue of blood vessels, hence lowering blood pressure. Other
reports describe roles of NO as an inhibitor for metalloenzymes
such as cytochrome P450, a cytochrome oxidase, nitrile
hydratase, and catalase, as a substrate for mammalian
peroxidases, and as a contributor to the vasodilator properties
of a salivary ferri-heme protein of blood sucking insects. Heme
centers are also involved in the in vivo generation of NO by
oxidation of arginine catalyzed by nitric oxide synthase enzymes.

3) For bioregulatory purposes, NO concentrations generated are
low, and [NO] values less than 1 micromolar have been reported
to be generated in endothelium cells for blood pressure control.
Thus, reactions with targets such as sGC must be very fast to
compete effectively with other physical and chemical processes
that deplete free NO. However, the NO concentrations produced
during immune response to pathogen invasion are much higher, and
under these conditions, reactive nitrogen species such as
peroxynitrite anion (OONO-) and N(sub2)O(sub3) may have
physiological importance. These biomedical roles place a high
premium on understanding the fundamental chemistry of NO under
conditions relevant to its biological formation and decay.

References (abridged):

1. (a) Moncada, S.; Palmer, R. M. J.; Higgs, E. A. Pharmacol.
Rev. 1991, 43, 109. (b) Feldman, P. L.; Griffith, O. W.; Stuehr,
D. J. Chem. Eng. News 1993, 71 (10), 26. (c) Butler, A. R.;
Williams, D. L. Chem. Soc. Rev. 1993, 233. (d) Methods in Nitric
Oxide Research; Feelisch M., Stamler, J. S., Eds.; John Wiley
and Sons: Chichester, England, 1996 and references therein. (e)
Wink, D. A.; Hanbauer, I.; Grisham, M. B.; Laval, F.; Nims, R.
W.; Laval, J.; Cook, J.; Pacelli, R.; Liebmann, J.; Krishna, M.;
Ford, P. C.; Mitchell, J. B. Curr. Top. Cell. Regul. 1996, 34,
159.

2. Nitric Oxide: Biology and Pathobiology; Ignarro, L. J., Ed.;
Academic Press: San Diego, 2000.

3. Schwartz, S. E.; White, W. H. Trace Atmospheric
Constitutents. Properties, Transformation and Fates; J. Wiley &
Sons: New York, 1983.

4. Nitric Oxide and Infection; Fang, F. C., Ed.; Kluwer
Academic/Plenum Publishers: New York, 1999.

5. (a) Traylor, T. G.; Sharma, V. S. Biochemistry 1992, 31,
2847. (b) Radi, R. Chem. Res. Toxicol. 1996, 9, 828.

Chem. Rev. 2002 102:993

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

4. BIOLOGY OF AGING: PUZZLES AND PROBLEMS

Most multicellular organisms exhibit a progressive and
irreversible physiological decline that characterizes what is
called "senescence" -- the aging process. The molecular basis of
this process is unknown, but various mechanisms have been
postulated, including: a) cumulative damage to DNA leading to
genome instability; b) biochemical pathway alterations that lead
to changes in gene expression patterns; c) telomere shortening
in replicative cells; d) oxidative damage to critical
macromolecules by reactive oxygen species; and e) nonenzymatic
*glycation of proteins. Experimental genetic manipulation of the
aging process in multicellular organisms has been achieved in
the fruit fly Drosophila through the overexpression of certain
enzymes, and in the nematode worm C. elegans through alterations
in the insulin receptor pathway, and in both organisms through
the experimental selection of stress-resistant mutants. In
mammals, however, the only intervention that appears to slow the
intrinsic rate of aging is caloric restriction. Most studies of
caloric restriction in mammals have involved laboratory rodents
subjected to a long-term 25 to 50 percent reduction in caloric
intake without essential nutrient deficiency, and the result in
these rodents is a delayed onset of age-associated pathological
and physiological changes and an extension of maximum lifespan.
Various mechanisms have been postulated to explain this result,
including increased DNA repair capacity, altered gene
expression, depressed metabolic rate, and reduced oxidative
stress.

M.R. Rose and A.D. Long (University of California Irvine, US)
discuss the biology of aging, the authors making the following
points:

1) Aging is a biological puzzle of long standing, particularly
because it manifests itself over a wide range of biological
systems, tissues and functions. For some time, the outstanding
task has been to find experimental strategies that make sense of
the complexity of aging. Some of the earliest experimental
research on aging was that of Raymond Pearl [3] on the duration
of life in Drosophila during the 1920s. But before 1980, little
progress was made in the study of aging in Drosophila. The
problem was that most of the tools of the genetics trade did not
give useful results. The large-effect mutants studied by Pearl
and colleagues almost always reduced life span. The Drosophila
mutants that enhanced life span most eliminated the reproductive
organs of females [4] , making such mutants of doubtful
relevance. A new crop of mutants that extend Drosophila life
spans have been produced (5), but it is not yet clear whether
any of these will reveal the physiology of normal aging.

2) Most biological research attempts to uncover functional
pathways, whether specific biochemical reactions or large-scale
developmental processes. Such pathways are built by natural
selection, and thus have attributes that are "well-designed",
even though there is no designer. Mutation and other genetic
tricks that modify functional pathways usually impair their
operation, and in so doing they reveal how those pathways
operate. This is why genetics is perhaps the most powerful tool
in the biologist's toolbox. It exposes functions, and teases
them apart.

3) But aging is not a function. Aging can be defined as an
endogenous progressive deterioration in age-specific components
of fitness [6] . It is not actively selected for. It is instead
a secondary effect of the decline in the force of natural
selection with age [7]. From such theory it follows that many
loci, and many biochemical pathways, are expected to produce the
deleterious effects of aging, because it is a secondary
side-effect of normal evolution. Earlier, less definitive work
using selected stocks indicated that many loci contribute to
aging in Drosophila.

References (abridged):

3. Pearl, R. (1922). The Biology of Death. (Lippincott,
Philadelphia).

4. Maynard Smith J. (1958) The effects of temperature and of
egg-laying on the longevity of Drosophila subobscura J. Exp.
Biol., 35:832-842.

5. Lin Y.J., Seroude L. and Benzer S. (1998) Extended life-span
and stress resistance in the Drosophila mutant methuselah
Science, 282:943-946.

6. Rose, M.R. (1991). Evolutionary Biology of Aging. (Oxford
Univ. Press).

7. Hamilton W.D. (1966) The moulding of senescence by natural
selection. J. Theor. Biol, 12:12-45.

Current Biology 2002 12:R311

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

5. THE NEW PLANETARY BIOLOGY

With the completion of genome sequences, the current challenge
for biology is to determine the functions of all gene products
and to understand how they contribute in making an organism
viable. For the first time, biological systems can be viewed as
being finite, with a limited set of molecular parts. However,
the full range of biological processes controlled by these parts
is extremely complex. Thus, a key approach in genomic research
is to divide the cellular contents into distinct sub-
populations, which are often given an "-omic" term. For example,
the "proteome" is the full complement of proteins encoded by the
genome, and the "secretome" is the subset of proteins secreted
from the cell. (D. Greenbaum et al: Genome Research 2001 11:1463)

S.A. Benner et al (University of Florida, US) discuss planetary
biology, the authors making the following points:

1) A key goal for biology in the postgenomic era is to use the
sequences of genes and proteins to generate information about
molecular, cellular, and organismal biology. In the future as in
the past, much of this information will undoubtedly be obtained
through biochemical, genetic, and molecular biological
experiments in the laboratory. This notwithstanding, almost any
approach that provides inferences, insights, or information
about biology from sequence data without requiring additional
experimentation will be valuable.

2) For this reason, considerable attention has been directed
toward the fact that biomolecular sequences contain information
about their historical past (1). The search for homologs, or
protein sequences that diverged from a common ancestor, is
frequently the principal tool used to annotate sequence
databases. Likewise, the sequences of a set of homologous
proteins suggest a tree that defines the history of the protein
family. These trees can be used to infer familial relationships
between the organisms that carry the proteins, define the order
in which particular taxa diverged (2, 3), constrain the
connectivity of the deep branches joining the primary kingdoms
of life (4), and even correlate the divergence of species with
their migrations across drifting continents (5).

3) This theme has been amplified by recognizing that two other
fields, geology and paleontology, also provide records of the
history of life on Earth. In many respects, these records
complement the record contained in molecular sequence data. For
this reason, considerable effort is now been directed toward
explicit connection of these three records. Here, the past is
the key to the present. By understanding the history by which a
protein emerged within the context of its planetary biology, we
hope to better understand how it functions in contemporary life.

4) In summary: The history of life on Earth is chronicled in the
geological strata, the fossil record, and the genomes of
contemporary organisms. When examined together, these records
help identify metabolic and regulatory pathways, annotate
protein sequences, and identify animal models to develop new
drugs, among other features of scientific and biomedical
interest. Together, planetary analysis of genome and proteome
databases is providing an enhanced understanding of how life
interacts with the biosphere and adapts to global change.

References (abridged):

1. L. Pauling, E. Zuckerkandl, Acta Chem. Scand. 17 (Suppl. 1),
S9 (1963)

2. F. G. R. Liu, et al., Science 291, 1786 (2001)

3. W. J. Murphy, et al., Science 294, 2348 (2001)

4. R. F. Doolittle, D. F. Feng, S. Tsang, G. Cho, E. Little,
Science 271, 470 (1996)

5. S. B. Hedges, Proc. Natl. Acad. Sci. U.S.A. 98, 1 (2001)

Science 2002 296:864

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

6. ON TAXONOMY

In science, assigning names to various objects is essential to
communication between researchers, and often important in
recognizing natural orders of systems. In the physical sciences,
the atmosphere of the Earth contains what is considered a high
order of variety of components, with 17 different known gases
varying in chemical and physical properties, distribution, and
interactions. In the biological sciences, the biosphere of the
Earth contains 2 million existing species of plants and animals,
with an estimated 10 to 30 million more species still to be
identified. And within each species, there is enough individual
diversity to sustain microclassifications. Confronted with such
an enormous diversity of components of the biosphere, biologists
are forced to focus on classification and nomenclature schemes
in order to avoid intellectual chaos.

Carolus Linnaeus (1707-1778) (Carl Linnaeus; Carl von Linn,) was
a botanist and explorer who is generally considered the first to
frame principles for defining genera and species and the first
to create a uniform system for naming such genera and species.
The revolutionary advance of Linnaeus was in nomenclature, the
introduction of a Latin binomial system: each species received a
Latin name, which was not influenced by local names and which
invoked the authority of Latin as a language common to the
educated people of that time. The Latin name has two parts: the
first word is capitalized and indicates the genus; the second
word is not capitalized and is the name of the species within
that genus. In addition to species and genera, Linnaeus also
recognized other classifications or "taxa" (singular, taxon)
which are still used: order, class, and kingdom. To these taxa
have been added "family" (between genus and order), and "phylum"
(between class and kingdom). Each taxon can be divided further
by an appropriate prefix sub- or super-. The monumental
monograph by Linnaeus, _Systema naturae_ (1735), published when
Linnaeus was all of 28 years old, went through 12 editions
during his lifetime, the 13th and final edition appearing
posthumously.

Linnaeus identified species on the basis of idealized
morphology. In the 20th century, a "new systematics" was
introduced, a new classification scheme designed to reflect
evolutionary history. The basic unit of classification, the
species, is also the basic unit of evolution, i.e., a population
of actually or potentially interbreeding individuals, with such
a population sharing, via interbreeding, its genetic resources.
This creates the population "gene pool", the total genetic
material of the population, the gene pool determining the
biological resources of the species, the resources upon which
natural selection continuously operates. Thus, current
systematics in biology tends to classify living systems in terms
of evolutionary history (phylogeny), and modern taxonomists
(systematists) are among the foremost students of evolution.

H. Charles Godfray (Imperial College Silwood Park, UK) discusses
taxonomy, the author making the following points:

1) Taxonomy, the classification of living things, has its
origins in ancient Greece and in its modern form dates back
nearly 250 years, to when Linnaeus introduced the binomial
classification still used today. Linnaeus, of course, hugely
underestimated the number of plants and animals on Earth. As
subsequent workers began to describe more and more species,
often in ignorance of each others' work, the resulting confusion
and chaos threatened to destroy the whole enterprise while still
in its infancy. In today's jargon, we might call this the first
bioinformatics crisis. Using the tools then available, 19th
century taxonomists solved this crisis in a brilliant way that
has served the subject well since then. They invented a complex
set of rules that determine how a species should be named and
associated with a type specimen; how generic and higher
taxonomic categories should be handled; and how conflicts over
the application of names should be resolved. All these rules
revolved around publications in books and scientific journals,
and their descendants form the current codes of zoological and
biological nomenclature. But today much of taxonomy is perceived
to be facing a new crisis _ a lack of prestige and resources
that is crippling the continuing cataloguing of biodiversity. In
the UK, a Parliamentary Select Committee is currently conducting
an enquiry into the health of the subject for the second time in
10 years, and similar concerns are being expressed around the
world.

2) Why can't descriptive taxonomy attract large-scale funds in
the same way as other big programs like the Human Genome Project
or the Sloan Digital Sky Survey? All three projects are enabling
science: not in themselves generating new ideas or testing
hypotheses, but allowing many new areas of research to be opened
up. One reason is that taxonomists lack clearly achievable goals
that are both realistic and relevant. Of course it would be
wonderful to describe every species of organism on Earth, but we
are still monumentally uncertain as to how many species there
are (probably somewhere between 4 million and 10 million); this
goal is just not realistic at present. There are various
projects aimed at listing, for example, all the valid described
species of animals in Europe, or butterflies on Earth. These
aims are eminently achievable and very worthwhile, but the
results are like raw and unannotated DNA sequences: unexciting
and of relatively little value in themselves to non-specialists.
Taxonomists need to agree on deliverable projects that will
receive wide support across the biological and environmental
sciences, and attract public interest.

3) A second problem is part of the legacy of more than 200 years
of systematics. Many taxonomists spend most of their career
trying to interpret the work of nineteenth-century
systematicists: deconstructing their often inadequate published
descriptions, or scouring the world's museums for type material
that is often in very poor condition. A depressing fraction of
published systematic research concerns these issues. In some
taxonomic groups the past acts as a dead weight on the subject,
the complex synonymy and scattered type material deterring
anyone from attempting a modern revision. As Frank-Thorsten
Krell recently pointed out (Nature 415, 957; 2002), "original
descriptions have to be referred to for ever, independent of the
paper's quality".

Nature 2002 417:17

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

7. MOLECULAR STRUCTURE THEORY AND ELECTRON COUNTING RULES

In this context, the term "Wade's rule" refers to an
electron-counting rule, first formulated in 1971, that states
that a cage molecule with a geometry based on a closed
polyhedron constructed of triangles with n vertices will possess
n + 1 skeletal bonding electron pairs. Wade's rule and its
corollaries -- collectively known as "Wade's rules" -- have been
refined and extended by a number of researchers. When coupled
with spectroscopic studies and theoretical calculations, these
rules have been successful in demonstrating the structural
interconnections between boranes, carboranes, other
heteroboranes, carbocations, organometallic complexes, and
transition-metal cluster compounds

Electron-counting rules for other and simpler structures have
been a feature of theoretical chemistry for nearly a century.
The "Lewis octet rule", formulated by G.N. Lewis (1875-1946) in
the 1920s, states that special stability is produced by filling
of the 2s and 2p atomic orbitals to achieve the electronic
configuration of neon, a noble gas. The "Hueckel rule",
formulated in the early 1930s by Erich Hueckel (1896-1984),
states that aromatic systems will contain 4n+2 pi electrons,
where (n) is an integer, 0,1,2,3....

E.D. Jemmis et al (University of Hyderabad, IN) discuss electron
counting rules, the authors making the following points:

1) Among several theoretical tools available for investigating
molecular structure, there is always a balance between
simplicity and reliability. While detailed electronic structure
calculations are more accurate and reliable, the computed
results are too difficult to interpret owing to the higher
complexity of the model and do not in general provide
information that can be transferred from one molecule to
another. Simple models such as Hueckel and the extended Hueckel
theory -- where the requirement is the topology or the
geometrical arrangement -- lead to an easy understanding of the
concerned molecular system though quantitative reliability is
lost. Even at this level, transferability of information is
achieved by formulating electron-counting rules of general
applicability. They give Boolean information, i.e., a true or
false answer, to the most basic question, whether a molecule in
a particular geometry with a given number of electrons is stable.

2) Electron-counting rules (e.g., the Lewis octet rule) lead to
a systematic expansion of knowledge concerning a set of
molecules of interest, by permitting the incorporation of
experimental and theoretical findings within a logically
consistent and reasonably simple framework. Its most significant
aspect is to reduce the complexity of the full problem of a
large number of experimental observations, by presenting an
abstract generalization in the concerned domain. The most
prevalent conviction about electron-counting rules is to
consider them as facts, and molecules that are not following
these rules are termed as disobedient. On the contrary, an
electron-counting rule is merely an unsubstantiated hypothesis
or a speculation concerning reality, which will become useful
only when appropriate confirmatory data have been obtained.
Though exceptions occur in significant amounts for all these
rules, they still represent a considerable step forward in
chemical reasoning, and often these exceptions lead to further
research and improved understanding.

3) The authors report an analysis of three-dimensional aromatic
(1,2) macropolyhedral boranes, for which research is considered
as largely exploratory and the underlying principles that govern
their stability are mostly unknown.(3) The importance of
electron counting, led by Wade's rule, is well realized,
especially in the domain of monopolyhedral boranes.(4) The
authors use a recently developed generalized electron-counting
scheme,(5) the "MNO rule". This rule is applicable to
macropolyhedral boranes, heteroboranes, and metallaboranes and
provides the borane chemist a new way to explain familiar
macropolyhedral systems and predict new and interesting
structures.

References (abridged):

1. (a) King, R. B.; Rouvray, D. H. J. Am. Chem. Soc. 1977, 99,
7834. (b) King, R. B. Chem. Rev. 2001, 101, 1119.

2. (a) Aihara, J.-I. J. Am. Chem. Soc. 1978, 100, 3339. (b)
Aihara, J.-I. J. Am. Chem. Soc. 1976, 98, 2750. (c) Aihara,
J.-I. J. Org. Chem. 1977, 99, 2048. (d) Aihara, J.-I. Bull.
Chem. Soc. Jpn. 1977, 50, 2010. (e) Gutman, I.; Milun, M.;
Trinajstic, N. J. Am. Chem. Soc. 1977, 99, 1692.

3. (a) Kennedy, J. D. In Advances in Boron Chemistry; Siebert,
W., Ed.; Royal Society of Chemistry: Cambridge, U.K., 1997; p
451. (b) Grimes, R. N. Metal Interactions with Boron Clusters;
Plenum Press: New York, 1982. (c) McGrath, T. D.; Jelinek, T.;
Stibr, B.; Thornton-Pett, M.; Kennedy, J. D. J. Chem. Soc.,
Dalton Trans. 1997, 2543.

4. (a) Wade, K. Electron Deficient Compounds; Nelson: London,
1971. (b) Wade, K. In Electron Deficient Boron and Carbon
Clusters; Olah, G. A., Wade, K., Williams, R. E., Eds.; Wiley:
New York, 1991.

5. Balakrishnarajan, M. M.; Jemmis, E. D. J. Am. Chem. Soc.
2000, 122, 4516.

Chem. Rev. 2002 102:93

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

8. QUANTUM THEORY: ON BELL INEQUALITIES

Quantum entanglement between two particles means that measuring
the behavior of one particle instantly determines the behavior
of the other particle, even when they are physically far apart.
Erwin Schroedinger (1887- 1961) once described this peculiar
connection as "_the_ characteristic trait of quantum mechanics,
the one that enforces its entire departure from classical lines
of thought." Entanglement describes a system with several
components in which the individual parts carry no information
but nevertheless share quantum correlations with each other that
are stronger than those allowed by classical physics. For
example, photons can be polarized -- the polarization describes
the oscillation direction of the electric field associated with
a light wave. Polarization filters, such as Polaroid sunglasses,
will let through photons polarized in one plane but block those
polarized at right angles, and so can be used to measure photon
polarization. If two photons have entangled polarizations, each
photon individually would appear completely unpolarized (with no
particular oscillation direction) and yet measuring the
polarization of one completely determines to polarization of the
other. It is as if you flipped two coins, each of which was
equally likely to come up heads or tails, and yet they always
gave the same results -- that is, both heads or both tails.
Although normal coins do not behave like this, it has been known
for some time how to produce pairs of photons that do display
such bizarre quantum-mechanical correlations. (Paul Kwiat:
Nature 2001 412:866)

A "hidden variables theory" is one of a class of physical
theories which deny that the quantum state of a physical system
is a complete specification. The hidden variables are those
components of the hypothetical complete state that are not
contained in the quantum state.

"Bell's inequality", formulated by John Bell (1928-1990) in
1964, is one of a family of inequalities concerning the
probabilities of joint occurrence of certain events in two well-
separated parts of a composite system, the inequality implied by
any hidden variables theory that satisfies an appropriate
locality condition. In this context, in general, a locality
condition is a condition such that no interaction between two
entities can occur in less time than the time required for light
to travel from one entity to the other. For example, any
apparent instantaneous effect of one entity upon the other
entity implies locality is not obeyed.

"Bell's theorem" is the theorem that no hidden variables theory
satisfying an appropriate locality condition can make
statistical predictions in complete agreement with those of
quantum mechanics. In other words, there are situations in which
quantum mechanics predicts a violation of Bell's inequality.
Another formulation is that any hidden variables theory that
forbids instantaneous interactions cannot make predictions in
complete agreement with those of quantum mechanics.

Einstein, Podolsky, and Rosen (EPR) (1935) designed a gedanken
experiment that suggested a theory that was more complete than
quantum mechanics. The EPR design was later realized in various
forms, with experimental results close to the quantum mechanical
prediction. The experimental results by themselves have no
bearing on the EPR claim that quantum mechanics must be
incomplete nor on the existence of hidden parameters. However,
the well known inequalities of Bell are based on the assumption
that local hidden parameters exist, and when combined with
conflicting experimental results, do appear to prove that local
hidden parameters cannot exist. This fact leaves only
instantaneous actions at a distance (called "spooky" by
Einstein) to explain the experiments. (K. Hess and W. Philipp:
Proc. Nat. Acad. Sci. 2001 98:14224,14228)

The term "Schroedinger's cat" refers to a thought experiment
introduced by Erwin Schroedinger (1887-1961) in 1935 to
illustrate the paradox in quantum mechanics regarding the
probability of finding a quantum entity (e.g., a subatomic
particle) at a specific point in space. Schroedinger postulated
a sealed box containing a live cat and a device triggered by a
quantum event, e.g., the radioactive decay of a nucleus. If the
quantum event occurs, cyanide is released and the cat dies; if
the event does not occur, the cat lives. According to
conventional quantum mechanics and the so-called "Copenhagen
interpretation" by Niels Bohr (1885-1962), the position of a
quantum particle remains indeterminate until it has been
observed. Shroedinger argued that the consequence is that the
cat can only be said to be alive or dead when the box has been
opened and the situation inside the box has been observed. Until
the moment of observation, the cat is both dead and alive, in a
"smeared" superposition of states. Paradox or no paradox, one
major point is that quantum reality strains the limits of
language developed and evolved to deal with ordinary reality.

D. Collins et al (University of Bristol, UK) discuss Bell
inequalities, the authors making the following points:

1) One of the most remarkable aspects of quantum mechanics is
its predicted correlations. Indeed, the correlations between
outcomes of measurements performed on systems composed of
several parts in an entangled state have no classical analog.
The most striking aspect of this characteristic feature of
quantum physics is revealed when the parts are spatially
separated: no classical theory based on local variables can
reproduce the quantum correlations. Historically, this became
known as the Einstein-Podolsky-Rosen paradox and was formulated
in terms of measurable quantities by Bell [1] and by Clauser,
Home, Shimony, and Holt [2] as the nowadays famous inequalities.
Other aspects of quantum correlation were analyzed in the form
of paradoxes, such as Schroedinger's cat and the measurement
problem. In recent years, these paradoxical aspects have been
overthrown by a more effective approach: "let us exploit
'quantum strangeness' to perform tasks that are classically
impossible" has become the new leitmotiv. From this "conceptual
revolution", the field of quantum information emerged. Old words
became fashionable, such as "entanglement". Old questions were
revisited, such as the classifications of quantum correlations.

2) The variety of known partial results, in particular, about
entanglement measures, makes it today obvious that there is no
one-parameter classification of entanglement. The authors report
an analysis of classifications related to what is called
"quantum nonlocality", i.e., the impossibility to reproduce
quantum correlations with theories based on local variables
(often called "local realistic theories"). The authors report
they have developed a novel approach to Bell inequalities based
on a constraint that the correlations exhibited by local
variable theories must satisfy. This is used to construct a
family of Bell inequalities for bipartite quantum systems of
arbitrarily high dimensionality which are strongly resistant to
noise. The authors suggest that in particular their work gives
an analytic description of previous numerical results and
generalizes them to arbitrarily high dimensionality.

References (abridged):

1. J.S. Bell, Physics (Long Island City, N.Y.) 1, 195 (1964).

2. J.F. Clauser, M.A. Home, A. Shimony, and R.A. Holt, Phys.
Rev. Lett. 23, 880 (1969).

Phys. Rev. Lett. 2002 88:040404

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

9. ASTROPHYSICS: ON RELATIVISTIC JETS

The term "active galactic nuclei" refers to central regions of
galaxies in which considerable energy is generated by processes
other than those operating in ordinary stars. The energy may
result from the accretion of material into a massive black hole
situated at the core of the galaxy.

A "quasar" (quasi-stellar objects) is an 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.

The term "Seyfert galaxy", named after Carl K. Seyfert
(1911-1960) refers to a type of galaxy with a small bright
nucleus exhibiting broad strong emission lines in its spectrum.
Seyfert galaxies apparently have active galactic nuclei that
produce the strong radiation, and these galaxies may be examples
of low-luminosity quasar activity.

The unmanned satellite called the "Chandra X-Ray Observatory"
was launched in 1999. This instrument was formerly called the
Advanced X-ray Astrophysics Facility, but it was renamed in
honor of the astrophysicist Subrahmanyan Chandrasekhar
(1910-1995). The Chandra instrument is equipped with a nested
array of mirrors to focus x-rays on two cameras that can produce
highly detailed images or high-resolution spectra of sources of
x-ray emissions.

A.C. Fabian (University of Cambridge, UK) discusses relativistic
jets, the author making the following points:

1) Most galaxies, including our own, appear to have a massive
black hole at their center. Some, the active galactic nuclei,
are visible to us as a result of luminous outpourings such as
quasars and the less powerful Seyfert galaxies. Approximately
10% of active galactic nuclei are strong radio emitters.
Diametrically opposed pairs of powerful energetic jets squirt
out of these "radio-loud" objects at relativistic speeds. The
jets themselves are rarely detected: the strongest evidence for
their existence may be a pair of lobes of radio-emitting
material on either side of the nucleus where the jets are
shocked and decelerated by surrounding gas.

2) The first of these jets was sighted by H. Curtis almost 90
years ago in the giant elliptical galaxy M87 in the Virgo
cluster. Twin radio lobes were reported almost 50 years ago. Yet
the matter content of jets (apart from the emitting electrons),
their total power, and their evolution remain uncertain. The
high spatial resolution x-ray imaging achieved by NASA's Chandra
observatory is, however, beginning to answer these questions.
X-ray observations have proven so useful because the gaseous
atmospheres that fuel the jets usually have temperatures on the
order of 10^(6) to 10^(7) kelvins. By studying the surrounding
gas, particularly bubbles in the gas blown by the jets, their
total power and history over the past 10^(7) to 10^(8) years can
be deduced. Holes and depressions in the x-ray emission have now
been seen around radio sources in numerous clusters, including
the Virgo cluster, the Perseus cluster, Hydra A, and the
Centaurus cluster (1-5).

3) The relativistic jets are believed to originate very close to
the central black hole and are probably ejected up the rotation
axis of the accreting gas, or the spin axis of the black hole
itself. As the jet decelerates in the surrounding matter, a
bubble of low-density heated gas and relativistic plasma
accumulates about the end of the jet. Unless the jet is so
powerful that it dominates the hot gas, the bubble expands until
buoyancy forces cause it to rise up and break away as a new
bubble forms. The situation is similar to that of a dripping
tap, with relative densities and directions reversed.

References (abridged):

1. H. Bohringer et al., Mon. Not. R. Astron. Soc. 264, L25 (1993)

2. A. C. Fabian et al., Mon. Not. R. Astron. Soc. 318, L65 (2000)

3. B. R. McNamara et al., Astrophys. J. 534, L135 (2000)

4. J. S. Sanders, A. C. Fabian, Mon. Not. R. Astron. Soc. 331,
273 (2002)

5. A. J. Young, A. S. Wilson, C. G. Mundell, in preparation
(available at http://xxx.lanl.gov/abs/astro-ph/0202504)

Science 2002 296:1040

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

10. ON THE RESORCINARENES

M. He et al (Louisiana State University, US) discuss the
resorcinarenes, the authors making the following points:

1) In 1872, a year after his landmark synthesis of the xanthene
dye fluoresceine,(1) J.F. Baeyer (1835-1917) studied the
condensation reaction of benzaldehyde and resorcinol in the
presence of acid.(2) The red solution containing his product
mixture changed to violet upon the addition of base. It is now
well known that Baeyer's reaction afforded the first
resorcinarenes, cyclic tetramers of resorcinol.(3) The broad
impact of the resorcinarenes in the fields of molecular
recognition, materials science, and supramolecular chemistry has
been the subject of extensive study as noted in several recent
reviews.(3) For instance, they were the first compounds shown to
bind sugars in apolar media.(4) Because boronic acids are the
basis of carbohydrate affinity chromatography, the authors
reasoned that resorcinarenes functionalized with boronic acids
would constitute powerful sugar receptors. The authors therefore
synthesized resorcinarenes and investigated their properties in
the presence of sugars.(5)

Sugars are a relatively challenging class of compounds to
analyze, exhibiting great structural similarity as well as
transparency in the visible region. The sensing of specific
saccharides could aid the monitoring of disease or industrial
fermentation products. The visual determination of saccharides
has been of interest for well over a century. Resorcinol and its
derivatives have long been used in simple color tests for
sugars. In 1887, Seliwanoff reported a resorcinol color test
which was followed by other resorcinol-derived methods. These
latter and numerous other related reducing sugar assays, while
based on simple reagents, typically require toxic materials,
harsh and often tedious procedures. In the 1990s, significant
progress was made toward the improved selective and mild
detection of monosaccharides via relatively strong solution
color changes observable by visual inspection. The recent
advances were due mainly to the pioneering efforts of Shinkai
and co-workers. Their studies were based primarily on
aniline-functionalized azo dyes containing appended arylboronic
acids.

The field of glycobiology has recently undergone great
resurgence due to the exciting therapeutic potential of
oligosaccharides. A vast number of oligosaccharides are found in
glycoproteins and on cell surfaces. Most of the recent progress
toward the color detection of sugars has, however, involved
monosaccharide analysis. The great variety of linear and
branched oligosaccharides magnifies the problems associated with
monosaccharide analysis.

In summary: The authors recently reported that solutions
containing resorcinarene macrocycles develop color upon heating
or standing. In the presence of saccharides, these solutions
exhibit significant color changes which are easily seen. We
herein present strong evidence that the solution color is due to
macrocycle ring opening and oxidation. The optical responses to
saccharides are due to complexation of the sugar with the
acyclic chromophores. We apply these mechanistic insights toward
the challenging problem of the visual detection of neutral
oligosaccharides by simple chromogens. In addition, we also
report the first single-crystal X-ray crystal structure
determination of a rarely observed "diamond" resorcinarene
stereoisomer.

References (abrdidged):

1. Baeyer, A. Chem. Ber. 1871, 5, 255.

2. (a) Baeyer, A. Ber. Dtsch. Chem. Ges. 1872, 5, 25. (b)
Baeyer, A. Ber. Dtsch. Chem. Ges. 1872, 5, 280.

3. (a) Schneider, H.-J.; Schneider, U. J. Inclusion Phenom.
1994, 19, 67. (b) Cram, D. J.; Cram, J. M. Container Molecules
and Their Guests; The Royal Society of Chemistry: Cambridge,
U.K., 1994. (c) Sherman, J. C. Tetrahedron 1995, 51, 3395. (d)
Timmerman, P.; Verboom, W.; Reinhoudt, D. N. Tetrahedron 1996,
52, 2663. (e) Jasat, A.; Sherman, J. C. Chem. Rev. 1999, 99,
931. (f) Rudkevich, D. M.; Rebek, J. Eur. J. Org. Chem. 1999, 9,
1991.

4. Aoyama, Y.; Tanaka, Y.; Sugihara, S. J. Am. Chem. Soc. 1989,
111, 5397.

5. Lewis, P. T.; Davis, C. J.; Saraiva, M.; Treleaven, W. D.;
McCarley, T. D.; Strongin, R. M. J. Org. Chem. 1997, 62, 6110.

J. Am. Chem. Soc. 2002 124:5000

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

11. CHEMISTRY: ON KENICHI FUKUI (1918-1998) AND ROALD HOFFMANN

In chemistry, the term "concerted reaction" refers in general to
a reaction in which there is a simultaneous occurrence of
bond-making and bond-breaking.

In this context, the "Woodward-Hoffmann rules" are rules
governing the formation of products during certain types of
organic concerted reactions. The theory of such reactions was
proposed in 1969 by Woodward and Roald Hoffmann, and is
concerned with the way orbitals of the reactants change
continuously into orbitals of the products during reaction and
with conservation of orbital symmetry during this process. The
theory is sometimes called "frontier orbital theory".

J. Van Houten (Saint Michael's College, US) discusses the Nobel
laureates Fukui and Hoffman, the author making the following
points:

1) During the first eight decades of the 20th century only six
Nobel Prizes (1) were awarded for work related to chemical
dynamics. The 1981 Nobel Prize awarded to Kenichi Fukui and
Roald Hoffmann represents the first of three Prizes for work in
chemical dynamics during the decade of the 1980s. Unlike all the
previous awards in chemical dynamics, the 1981 award recognized
work that was more theoretical and that allowed chemists to
predict in advance the course and the ultimate products of
certain reactions.

2) As their official Nobel citation (2) states, the 1981
Laureates developed theories independently that led to what has
come to be known collectively as the theory of conservation of
orbital symmetry. Fukui, working in Japan, developed "frontier
orbital theory" beginning in 1952. Hoffmann, working initially
with Robert Burns Woodward at Harvard in 1964, developed a
principle of conservation of orbital symmetry in chemical
reactions that was first described in a series of communications
(3) appearing in the Journal of the American Chemical Society in
1965. The correlation diagrams that are often associated with
the so-called "Woodward-Hoffmann rules" appeared in 1965 in
back-to-back papers authored by H. C. Longuet-Higgins and E. W.
Abrahamson (4) and by Hoffmann and Woodward (3b).

3) The name "Woodward-Hoffmann rules" has led some to the
misconception that Woodward and Hoffmann shared a Nobel Prize.
Woodward did win a Nobel Prize in 1965 for "outstanding
achievements in the art of organic synthesis" (5), but his
untimely death in 1979 made him ineligible for a second Prize in
1981. Hoffmann has observed that all the award nominations prior
to Woodward's death were for the two of them together. He is
certain that had Woodward lived, he would have won a share of
the 1981 Prize, thereby becoming only the second person to win
two chemistry Nobel Prizes.

4) Kenichi Fukui was the first_and until the awards in 2000 and
2001 to Hideki Shirakawa and Ryoji Noyori, the only -- Japanese
chemist to win a Nobel Prize. Fukui graduated from Kyoto
Imperial University in 1941 and was engaged in research on
synthetic fuels for the Japanese Army during World War II. He
became a lecturer in Fuel Chemistry at Kyoto Imperial University
in 1943, received his Ph.D. in engineering in 1948 and was named
professor in 1951 (2)

5) Roald Hoffmann is the second Polish emigre to receive the
chemistry Nobel Prize_the first was Marie Sklodowska Curie (22).
He was born in 1937 in Zioczow. (The town was part of
Austria-Hungary when his parents, Hillel Safran and Clara Rosen,
were born, was in Poland at the time of his birth, became part
of the Soviet Union after World War II, and is now part of the
Ukraine.).

References (abridged):

1. a. Van Houten, J. Chem. Educ. 2001, 78, 1572-1573; b. ibid,
2002, 79, 21-22; c. ibid, 2002, 79, 146-148; d. ibid, 2002, 79,
301-304; e. ibid, 2002, 79, 414-416; f. ibid, 2002, 79, 548-550.

2. Nobel e-Museum-Chemistry 1981 (with links to Prize
Presentation and Biography pages),
http://www.nobel.se/chemistry/laureates/1981/index.html

3. a. Woodward, R. B.; Hoffmann, R./. Am. Chem. Soc. 1965, 87,
595-397; b. Hoffmann, R.; Woodward, R. B. ibid, 1965, 87,
2046-2048; c. Hoffmann, R.; Woodward, R. B. ibid, 1965, 87,
4389-4390.

4. Longuet-Higgins, H. C.; Abrahamson, E. W. /. Am. Chem. Soc.
1965,87, 2045-2046.

5. Nobel e-Museum-Chemistry 1965 (with links to Prize
Presentation and Biography pages),
http://www.nobel.se/chemistrylla.ureatesll9651index.html

J. Chem. Ed. 2002 79:668

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

12. ON ORGANIC CHEMICAL SYNTHESIS

Stephen J. Lippard (Massachusetts Institute of Technology, US)
discusses chemical synthesis, the author making the following
points:

1) A key goal in synthetic organic chemistry is the design of
reagents to achieve chemical transformations at specific sites
in a molecule without protection and deprotection steps. To
achieve one stereoisomer to the exclusion of its mirror image is
a further, often more difficult, challenge, as is the
development of catalysts that promote an efficient chemical
transformation. The synthetic inorganic chemist faces a
different but equally formidable task of control. Consider the
goal of preparing a catalyst for a chemical transformation that
occurs in living organisms at ambient temperature and pressure,
such as the conversion of atmospheric nitrogen to ammonia,
natural gas to methanol, or water to hydrogen. The first of
these catalysts would significantly assist in the fertilization
of crops; the second would allow methane to be transported much
more economically from remote gas wells to urban areas; and the
third would provide a key ingredient for fuel cells from a
non-carbon, replenishable fuel source.

2) The enzymes that catalyze such reactions in nature typically
operate at kilohertz frequencies: many biological chemical
reactions convert substrates to products at rates of roughly
1,000 per second. Almost half of these enzymes require metal
ions to achieve their catalytic functions -- usually Mg, Ca, Mn,
Fe, Co, Ni, Cu and Zn -- typically embedded in a
three-dimensional protein matrix that ensures tightly controlled
alignment of the reactants to achieve the desired formation and
release of the product molecule(s). Outside the protein milieu,
these metals in their typical + 2 and + 3 oxidation states form
complexes that exchange their ligands rapidly -- they are
kinetically labile.

3) These ions seem, therefore, to have been adopted by living
organisms precisely because they can bind to substrates and
release products on a timescale commensurate with biological
requirements. Notably absent from the list are second- and
third-row transition metals, such as Ru, Pd and Pt. Complexes
containing these metal ions are important as industrial
catalysts, but their rates of ligand exchange are much lower
than those of their first-row counterparts. With a few
exceptions, such as Mo and W, such elements have therefore not
been selected for biological functions.(1-5)

References:

1. Lippard, S. J. Chem. Eng. News 78, 64-65 (2000).

2. DeGrado, W. F., Summa, C. M., Pavone, V., Nastri, F. &
Lombardi, A. Annu. Rev. Biochem. 68, 779-819 (1999).

3. Taft, K. L. et al. J. Am. Chem. Soc. 116, 823-832 (1994).

4. Watton, S. P. et al. Angew. Chem. 36, 2774-2776 (1997).

5. Leininger, S. et al. Chem. Rev. 100, 853-907 (2000).

Nature 2002 416:587

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

13. ELECTRIC CIRCUIT CONTROL OF DNA HYBRIDIZATION

In this context, the term "hybridization refers to the formation
of a macromolecular hybrid by the artificial recombination of
subunits, e.g., of polynucleotide strands.

K. Hamad-Schifferli et al (Massachusetts Institute of
Technology, US) discuss control of DNA hybridization, the
authors making the following points:

1) Increasingly detailed structural(1) and dynamic(2,3) studies
are highlighting the precision with which biomolecules execute
often complex tasks at the molecular scale. The efficiency and
versatility of these processes have inspired many attempts to
mimic or harness them. To date, biomolecules have been used to
perform computational operations(4) and actuation(5), to
construct artificial transcriptional loops that behave like
simple circuit elements, and to direct the assembly of
nanocrystals. Further development of these approaches requires
new tools for the physical and chemical manipulation of
biological systems. Biomolecular activity has been triggered
optically through the use of chromophores, but direct electronic
control over biomolecular "machinery" in a specific and fully
reversible manner has not yet been achieved.

2) Inductive coupling is the transfer of energy between
circuits. If the secondary circuit has finite impedance, eddy
currents are produced which are converted to heat by the Joule
effect. Heating a conductor by placing it in an alternating
magnetic field is generally used to heat macroscopic samples.

3) The authors report a demonstration of remote electronic
control over the hybridization behavior of DNA molecules by
inductive coupling of a radio-frequency magnetic field to a
metal nanocrystal covalently linked to DNA. Inductive coupling
to the nanocrystal increases the local temperature of the bound
DNA, thereby inducing denaturation while leaving surrounding
molecules relatively unaffected. Moreover, because dissolved
biomolecules dissipate heat in less than 50 picoseconds, the
switching is fully reversible. The authors suggest that although
inductive heating of macroscopic samples is widely used, the
present approach should allow extension of this concept to the
control of hybridization and thus of a broad range of biological
functions on the molecular scale.

References (abridged):

1. Ban, N., Nissen, P., Hansen, J., Moore, P. B. & Steitz, T. A.
The complete atomic structure of the large ribosomal subunit at
2.4 � resolution. Science 289, 905-920 (2000).

2. Deniz, A. A. et al. Single-molecule protein folding:
Diffusion fluorescence resonance energy transfer studies of the
denaturation of chymotrypsin inhibitor 2. Proc. Natl Acad. Sci.
USA 97, 5179-5184 (2000).

3. Davenport, R., Wuite, G., Landick, R. & Bustamante, C.
Single-molecule study of transcriptional pausing and arrest by
E. coli RNA polymerase. Science 287, 2497-2500 (2000).

4. Winfree, E., Liu, F., Wenzler, L. & Seeman, N. Design and
self-assembly of two-dimensional DNA crystals. Nature 394,
539-44 (1998).

5. Yurke, B. et al. A DNA-fuelled molecular machine made of DNA.
Nature 406, 605-608 (2000).

Nature 2002 415:152

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

14. ON THE ETIOLOGY AND TREATMENT OF SCHIZOPHRENIA

The diagnoses of various behavioral disorders are for the most
part made in the absence of defined etiology, and because of
this there is a necessary focus on symptoms rather than causes,
and the diagnostic categories are consequently often ambiguous
and labile. Schizophrenia is a serious mental disease (or
complex of mental diseases) that occurs worldwide with a
prevalence ranging from 0.2% to 1%. Its chief characteristic is
a chronic impairment of function involving disturbances of
thought, perception, feelings, and behavior, particularly the
appearance of the classical psychotic symptoms of delusions,
hallucinations, and logic dysfunction. A major worldwide mental
health problem, schizophrenia has been the focus of an enormous
number of research studies during the past century, and nearly
every possible etiology has been proposed to explain its
pathogenesis, including genetic mutations and viruses.

A. Sawa and S.H. Snyder (Johns Hopkins University, US) discuss
schizophrenia, the authors making the following points:

1) Most psychiatric disorders are classified as complex in
origin -- i.e., they cannot be easily explained by a single
genetic or environmental component. One of the most debilitating
of these disorders is schizophrenia, which affects approximately
1% of the population. Once the symptoms of schizophrenia occur
(usually in young adulthood), they persist for the entire
lifetime of the patient and are almost totally disabling.

2) How do we define schizophrenia? In the absence of a known
molecular abnormality, the diagnosis is based on the
simultaneous presentation of two types of symptoms that reflect
a psychotic disturbance: "positive" symptoms that include
delusions, hallucinations, and bizarre thoughts, and negative
symptoms that include social withdrawal with affective
flattening, poor motivation, and apathy. Patients with affective
disorders such as bipolar disorder may exhibit a subset of the
psychotic symptoms associated with schizophrenia, such as
hallucinations, but these disorders generally have a distinct
constellation of symptoms and familial incidence (1).

3) Efforts to identify the underlying disturbances in
schizophrenia are currently focused on three general lines of
inquiry: (i) examination of the mechanism of action of the drugs
that alleviate the symptoms of schizophrenia, (ii) examination
of neuroanatomical abnormalities in the brains of schizophrenia
patients, and (iii) examination of candidate genes that confer
susceptibility to schizophrenia.

4) There was no truly efficacious treatment for schizophrenia
until the early 1950s, when the beneficial effects of
chlorpromazine were discovered. This drug revolutionized patient
treatment: Besides calming down hyperactive patients, it
ameliorated the positive symptoms of the disorder, enabling
patients to leave mental hospitals and function moderately well
in society at large. Chlorpromazine and its successor drugs were
designated "neuroleptics," from the Greek term meaning "to clasp
the neuron." This designation was based on the pioneering work
of Jean Delay and Pierre Deniker, who observed that the
effective dose of chlorpromazine varied widely among patients.
Beneficial responses generally occurred at doses that elicited
neurologic side effects resembling Parkinson's disease.
Parkinson's disease is associated with degeneration of dopamine
neurons that project to the caudate putamen of the brain.
Through studies of dopamine turnover and direct measurements of
dopamine receptors, it was established that neuroleptics block
the D2 subtype of dopamine receptor (2, 3). Blockade of
receptors in the caudate putamen was found to cause the
neurologic side effects of the neuroleptics, and blockade of
receptors in limbic areas such as the nucleus accumbens and
prefrontal cerebral cortex of the brain -- which regulate
emotional behavior -- was found to account for the antipsychotic
effects of the drugs. Administration of amphetamines, which act
by releasing dopamine, was found to exacerbate schizophrenia
symptoms. These drug effects led to a "dopamine hypothesis" for
the modulation of schizophrenia symptoms, with excess dopamine
accentuating and decreased dopamine alleviating the symptoms
(2-4). Although the great majority of neuroleptics relieve only
the positive symptoms of schizophrenia, clozapine also relieves
the negative symptoms and can cause substantial improvement in
patients who fail to respond to other neuroleptics (5). The
great success of clozapine led to the development of several
"atypical" neuroleptics whose pharmacologic profile resembled
that of clozapine.

References (abridged):

1. N. C. Andreasen, Neuron 6, 697 (1996)

2. I. Creese, D. R. Burt, S. H. Snyder, Science 192, 481 (1976)

3. P. Seeman, T. Lee, M. Chau-Wong, K. Wong, Nature 261, 717
(1976)

4. A. Carlson, Neuropsychopharmacology 1, 179 (1988)

5. H. Y. Meltzer, in Psychopharmacology: The Fourth Generation
of Progress, F. E. Bloom, D. J. Kupfer, Eds. (Raven, New York,
1995), pp. 1277-1286

Science 2002 296:692

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

15. A GENETIC HYPOTHESIS FOR SCHIZOPHRENIA SUSCEPTIBILITY

Aravinda Chakravarti (Johns Hopkins University, US) discusses
genes and schizophrenia, the author making the following points:

1) The human genome sequence is facilitating the task of
identifying disease genes, understanding their normal functions
and why compromising their function is associated with specific
features of a disorder and its inheritance pattern (1). Genetic
disorders with simple dominant and recessive (Mendelian)
patterns of inheritance are invariably caused by rare
single-gene mutations that are both necessary and sufficient for
the disease to manifest. However, some single-gene disorders can
display a complex pattern of inheritance. The prototype for this
class is fragile X syndrome (2), whose non-Mendelian and complex
pattern of X-linked inheritance arises from dynamic evolution of
the mutation within families (3). Thus, complexity in
inheritance patterns is not inconsistent with single-gene
defects although geneticists routinely equate the non-Mendelian
nature of a trait with inheritance at multiple genes (4).
Genetic dissection of multigenic disorders is truly challenging
yet possible (5), particularly with the human genome sequence in
hand.

2) Schizophrenia is a common and severe mental illness of
thought, emotion, and behavior that affects approximately 1% of
the general population. It is a devastating disorder, probably
unique to humans, affecting not only the sufferers but also
their families. The intense familiality of schizophrenia has
been recognized for a long time and siblings of schizophrenics
have a 10-fold elevated susceptibility to the phenotype. The
familial nature of schizophrenia does not conform to simple
dominant or recessive modes of inheritance and, consequently,
identifying the underlying genes have proved difficult and
disease pathophysiology is still in doubt. Over the past three
decades, scores of psychiatrists and geneticists have grappled
with identifying the genetic determinants of schizophrenia, now
universally thought to reside at multiple genes. These genetic
mapping studies have proved to be frustrating because no single
chromosomal region appears paramount and genomic locations
identified by one group have seldom been replicated by others.
There are many possible reasons for this outcome, both
biological and methodological, but heterogeneity in disease
causation is thought to be the most likely cause.

3) One chromosomal region that appears to be contributory to
schizophrenia susceptibility is that on human chromosome 22q11.
Despite its inconsistent involvement across mapping studies, its
importance is demonstrated by the finding that 25-31% of
patients with microdeletions of chromosomal material at 22q11
met diagnostic criteria for schizophrenia and associated
disorders. These microdeletions are rare in the general
population but are 80 times more frequent in adult
schizophrenics and 240 times elevated in childhood-onset
schizophrenia. Although childhood onset of schizophrenia is
rare, this marked elevation of microdeletion frequency is a
terrific clue because it solidly implicates a genomic region, at
least for some cases of schizophrenia etiology. The specific
genes involved, however, remained a mystery, because the
deletions remove many genes.

References (abridged):

1. Jiminez-Sanchez, J. , Childs, B. & Valle, D. (2001) Nature
(London) 409, 853-855

2. Sherman, S. L. , Morton, N. E. , Jacobs, P. A. & Turner, G.
(1984) Ann. Hum. Genet. 48, 21-37

3. Jin, P. & Warren, S. T. (2000) Hum. Mol. Genet. 9, 901-908

4. Chakravarti, A. (1999) Nat. Genet. 21, 56-60.

5. Lander, E. S. & Schork, N. J. (1994) Science 265, 2037-2048

Proc. Nat. Acad. Sci. 2002 99:4755

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

16. ON THE PROBLEMS OF TOXICOLOGY

M. Lotti and P. Nicotera (University of Padua, IT) discuss
toxicology, the authors making the following points:

1) Several key advances in biology and medicine in the past were
brought about by studies of poisons. The eludication of the
mechanism of carbon monoxide toxicity by Claude Bernard
(1813-1878), which led to the understanding of the function of
hemoglobin, is a classic example. However, Jean-Pierre Changeux
and colleagues, who used alpha-bungarotoxin to purify
acetylcholine receptors, and William Catterall, who isolated
sodium channels using scorpion toxin, probably did not consider
themselves to be toxicologists. Has modern toxicology actually
provided new fundamental concepts? Surprisingly, with a few
notable exceptions, it has not _ it is nowadays regarded as an
applied science that is devoted to minimizing environmental
health risks posed by chemicals, mainly through risk assessment.

2) At the same time, there is an emerging crisis of confidence
in toxicology as an applied science that can effectively predict
risk, as illustrated by the debate about servicemen exposed to
depleted uranium from weapons during the Kosovo conflict in
1999. Although there is no evidence for radiological or chemical
carcinogenic risk at any conceivable level of exposure, the wide
perception of this issue has been very different. Predictions
based solely upon epidemiological projections without solid
scientific bases are often misleading. Examples include the
debates over genetically modified foods, dioxins, measles
vaccinations, and prion diseases in cattle and sheep. In the
case of prion diseases, there is a remarkably uncertain and
contradictory range of theoretical predictions for the size of
any future epidemic of variant Creutzfeld-Jakob disease in
humans.

3) There are surely various reasons for this failure of trust,
but the authors discuss one in particular. Perhaps because of
the immense scope of research into the mechanisms by which
individual compounds act, basic research has, over the past two
decades, become irrelevant to many toxicologists. A discipline
that mostly depends on others for fresh fundamental knowledge,
and is slow in acquiring it, will also be slow in its progress
and weak in its conclusions. Prejudice, ideology and
irrationality will undoubtedly grow. For instance, few among the
public appreciate the fact that hazard and risk are different
concepts. Hazard defines the potential of a compound to cause
harm and is therefore associated with virtually any molecule,
whereas a risk of adverse health effects relates to the level of
exposure and to individual susceptibility to that molecule. Such
misunderstanding may account for the generous public funds that
have been allocated to the study of dioxin toxicity, despite the
lack of evidence for effects on human health at current
environmental exposures.

4) Toxicology is being shaped by worldwide political agendas,
triggered by the public's desire for swift and precautionary
solutions to the possible health effects of environmental
chemicals. The resulting feedback loop has impoverished the
discipline, because its growth has largely been driven by the
demand for protocols for regulatory actions (1-5).

References (abridged):

1. Berry, C. Trends Pharmacol. Sci. 22, 277-280 (2001).

2. Golub, T. R.l. Science 286, 531-537 (1999).

3. Hoeijmakers, J. H. J. Nature 411, 366-374 (2001).

4. Smith, L. L. Trends Pharmacol. Sci. 22, 281-285 (2001).

5. Gibbons, M. Nature 402, C81-C84 (1999).

Nature 2002 416:481

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

17. DIABETES AND ATHEROSCLEROSIS

"Arteriosclerosis" is a generic term for several diseases in
which the arterial wall becomes thickened and loses elasticity,
and "atherosclerosis" is a form of arteriosclerosis
characterized by patchy thickening (atheroma) in the subintimal
layer (i.e., immediately below the innermost layer [intima]) of
medium and large arteries, the thickening capable of reducing or
obstructing blood flow.

The term "type 2 diabetes" refers to 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. In general, diabetes mellitus is 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.

J.A. Beckman et al (Harvard University, US) discuss diabetes and
atherosclerosis, the authors making the following points:

1) Clinical manifestations of atherosclerosis occur primarily in
3 vascular beds: coronary arteries, lower extremities, and
extracranial carotid arteries. Diabetes increases the incidence
and accelerates the clinical course of each. Coronary artery
disease causes much of the serious morbidity and mortality in
patients with diabetes, who have a 2- to 4-fold increase in the
risk of coronary artery disease.(2) In one population-based
study,(3) the 7-year incidence of first myocardial infarction or
death for patients with diabetes was 20% but was only 3.5% for
nondiabetic patients. History of myocardial infarction increased
the rate of recurrent myocardial infarction or cardiovascular
death events for both groups (18.8% in nondiabetic persons and
45% in those with diabetes). Thus, patients with diabetes but
without previous myocardial infarction carry the same level of
risk for subsequent acute coronary events as nondiabetic
patients with previous myocardial infarction. Such results led
the Adult Treatment Panel III of the National Cholesterol
Education Program to establish diabetes as a coronary artery
disease risk equivalent mandating aggressive antiatherosclerotic
therapy.(4)

2) Diabetes also worsens early and late outcomes in acute
coronary syndromes. In unstable angina pectoris or non-Q-wave
myocardial infarction compared with control, the presence of
diabetes increases the risk of in-hospital myocardial
infarction, complications of myocardial infarction, and
mortality.(5) In the OASIS registry, a 6-nation study of
unstable angina and non-Q-wave myocardial infarction, diabetes
independently increased the risk of death by 57%.(6) Regardless
of the severity of clinical presentation, patients who have
diabetes and coronary events experience increased rates of
myocardial infarction and death. Patients with diabetes also
have an adverse long-term prognosis after myocardial infarction,
including increased rates of reinfarction, congestive heart
failure, and death.(6)

3) The authors review the epidemiology, pathophysiology, and
medical and invasive treatment of atherosclerosis in patients
with diabetes mellitus. The authors conclude that since most
patients with diabetes die from complications of
atherosclerosis, they should receive intensive preventive
interventions proven to reduce their cardiovascular risk.

References (abridged):

2. Feskens EJ, Kromhout D. Glucose tolerance and the risk of
cardiovascular disease: the Zutphen Study. J Clin Epidemiol.
1992;45:1327-1334.

3. Haffner SM, Lehto S, Ronnemaa T, et al. Mortality from
coronary heart disease in subjects with type 2 diabetes and in
nondiabetic subjects with and without prior myocardial
infarction. N Engl J Med. 1998;339:229-234.

4. Executive summary of the third report of the National
Cholesterol Education Program (NCEP) Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults
(Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

5. Kjaergaard SC, Hansen HH, Fog L, et al. In-hospital outcome
for diabetic patients with acute myocardial infarction in the
thrombolytic era. Scand Cardiovasc J. 1999;33:166-170.

6. Malmberg K, Yusuf S, Gerstein HC, et al. Impact of diabetes
on long-term prognosis in patients with unstable angina and
non-Q-wave myocardial infarction: results of the OASIS
(Organization to Assess Strategies for Ischemic Syndromes)
Registry. Circulation. 2000;102:1014-1019.

J. Am. Med. Assoc. 2002 287:2570

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

18. ON THE FUTURE OF HEALTH INSURANCE IN THE US

Victor R. Fuchs (Stanford University, US) discusses health
insurance in the US, the author making the following points:

1) The announcement that most of the nation's biggest insurers _
Aetna, CIGNA, Humana, the United Health Group, and Wellpoint
Health Network
_ will be introducing a new kind of health plan during the next
year or two signals the beginning of a new era in health
insurance in the United States.(1) These plans feature a
complicated menu of premiums, copayments, and deductibles that
will add impetus to the trend of employers' offering a denned
contribution for health benefits. Each employee will get a fixed
amount of money to spend as he or she sees fit and will use the
Internet to "shop" for medical care. The plans will encourage
the use of medical savings accounts in combination with
catastrophic-illness insurance to cover expenditures that exceed
a large deductible. One of their major effects will be to shift
the burden of health care costs from employees who use little
care to those who use more. Thus, the new plans will be another
nail in the coffin of health insurance
as a form of social insurance.

2) At its inception, the health insurance system in the United
States was very much a social enterprise. Non-profit insurance
companies such as Blue Cross and Blue Shield and the Kaiser
Permanente Health Plan charged the same premium for everyone in
a community, so that the young and the healthy subsidized the
old and the sick. Hospitals also played a part in
cross-subsidization by not allocating charges fully to the
patients who made the greatest use of the hospital's resources.
Many physicians also contributed to the implicit social
insurance by providing care to sick poor persons at lower fees
or completely free of charge.

3) This system of social insurance began to erode when private
health insurance companies entered the market and instituted
policies that departed from the use of community-wide premiums.
They used the actuarial approach to insurance, charging lower
premiums for groups that were expected to use health care
services less. This practice enabled them to "skim the cream"
off the top of the health insurance market, and it drove up
costs for any plan that tried to continue to set the same
premium for everyone. Eventually, standard, community-wide
premiums virtually disappeared. Today, most large employers and
many medium-size ones are self-insured; they contract with
insurance companies for administrative services only. Other
employers are typically "experience-rated": their premiums are
periodically adjusted to take account of the health care
expenditures for their employees during the previous period.
Contracts for managed care also erode social insurance by
reducing or eliminating the ability of hospitals and physicians
to act as agents of redistribution through the
cross-subsidization of patients.

4) Self-insurance, experience-rating, and the spread of managed
care have ended the subsidization of health care across
employers. But there is still cross-subsidization within
individual organizations. The new health plans will erode this
type of subsidization as well. Once it does so, the only
remaining rationale for employment-based health insurance will
be the outdated, inequitable tax law that allows employers to
deduct their contributions to health insurance and allows
employees not to include the value of their health benefits in
their taxable income.

References abridged):

1. Freudenheim M. A new health plan may raise expenses for
sickest work-
ers. New York Times. December 5, 2001:A1.

New Engl. J. Med. 2002 346:1822

Related Background:

A SHARP CRITICISM OF US HEALTH INSURANCE POLICY

Brian Vastag (J. Am. Med. Assoc., US) discusses US health
insurance. A recent report of the Institute of Medicine says
that the jumble of health insurance schemes in the US "functions
more like a sieve than a safety net". The report paints a bleak
picture of the nation's uninsured. Nearly 18 percent of the US
lacks health coverage -- some 32 million to 42 million people, a
number exceeding the combined populations of Texas, Florida, and
Connecticut. The insurance gap hits working families (those with
at least one worker) particularly hard. A full 80 percent of
uninsured persons under age 65 live in working families; many
survive on low wages from service jobs. Families with two wage
earners fare better, but 10 percent of those families lack
health coverage. While the proportion of uninsured dropped in
1999 and 2000, it is expected to rise again due to ballooning
costs. Mary Sue Coleman, co-chair of the committee that wrote
the report and president of the Iowa Health System and the
University of Iowa (Iowa City) states: "More than the state of
the economy, the rising cost of health care services and
insurance premiums, combined with a hodgepodge of policies and
practices, undermines the affordability for employers, their
workers, and the public at large. In general in the US, millions
of adults and children rarely visit a physician, missing out on
care for chronic illnesses and opportunities for prevention.
With nowhere else to turn, they tend to seek care at emergency
departments, often only after health problems flare and become
intolerable.

J. Am. Med. Assoc. 2001 286:2223

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

19. ON ELECTRICAL DETECTION OF DNA

The term "polymerase chain reaction (PCR)" refers to a technique
for isolating and amplifying any specifically desired DNA
sequence. The reaction is facilitated by a heat-stable DNA
polymerase (e.g., Taq, which is obtained from a thermophilic
bacterium) that can withstand the many cycles of heating and
cooling involved in the technique. PCR is considered by many
molecular biologists to be the most important technical advance
in molecular biology in the second half of the 20th century. The
inventor of the technique, Kary Mullis, received the Nobel Prize
in Chemistry in 1993 for his discovery.

S-J. Park et al (Northwestern University, US) discuss detection
of DNA, the authors making the following points:

1) A major challenge in the area of DNA detection (1) is the
development of methods that do not rely on polymerase chain
reaction (PCR) or comparable target-amplification systems that
require additional instrumentation and reagents that are not
ideal for point-of-care or field use. Another restrictive
requirement of most DNA detection systems, regardless of their
need for PCR, is a thermal-stringency wash to differentiate
target strands from ones with mismatches and thus achieve
desired analyte selectivity. The authors have previously
reported several optical DNA detection methods based on
oligonucleotide-modified Au nanoparticles and their
size-dependent scattering, catalytic, and absorption properties
(2-5). The authors have demonstrated that Au particles that are
heavily functionalized with oligonucleotides exhibit
extraordinarily sharp thermal-denaturation profiles that
translate into higher target selectivities (2-5).

2) The authors now report a conductivity-based DNA detection
method utilizing oligonucleotide-functionalized Au nanoparticles
that provides an alternative to existing detection methods and
presents a straightforward approach to high-sensitivity and
high-selectivity, multiplexed detection of DNA. In the new
detection scheme, selective binding occurs between a shorter
"capture" oligonucleotide strand located in the gap between two
fixed microelectrodes and a longer "target" oligonucleotide in
solution. The target oligonucleotide has contiguous recognition
elements that are complementary to the capture strand on one end
and on the other to oligonucleotides attached to Au
nanoparticles. Therefore, when the device with the pair of
electrodes is immersed in a solution containing the appropriate
probe and target, Au nanoparticle probes fill the gap.

3) In summary: A DNA array detection method is reported in which
the binding of oligonucleotides functionalized with gold
nanoparticles leads to conductivity changes associated with
target-probe binding events. The binding events localize gold
nanoparticles in an electrode gap; silver deposition facilitated
by these nanoparticles bridges the gap and leads to readily
measurable conductivity changes. An unusual salt
concentration-dependent hybridization behavior associated with
these nanoparticle probes was exploited to achieve selectivity
without a thermal-stringency wash. Using this method, the
authors report they have detected target DNA at concentrations
as low as 500 femtomolar with a point mutation selectivity
factor of approximately 100,000:1.

References (abridged):

1. G. H. Keller, M. M. Manak, DNA Probes (Stocktonton, NY, 1989)

2. R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger,
C. A. Mirkin, Science 277, 1078 (1997)

3. J. J. Storhoff, R. Elghanian, R. C. Mucic, C. A. Mirkin, R.
L. Letsinger, J. Am. Chem. Soc. 120, 1959 (1998)

4. T. A. Taton, C. A. Mirkin, R. L. Letsinger, Science 289, 1757
(2000)

5. T. A. Taton, G. Lu, C. A. Mirkin, J. Am. Chem. Soc. 123, 5164
(2001)

Science 2002 295:1503

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

20. SULFURIC ACID DETERIORATION OF A 17TH CENTURY WARSHIP

The term "heterotrophic" (syn: organotrophic) refers to
organisms dependent on external sources of organic compounds as
a means of obtaining energy and/or materials.

M. Sandstrom et al (University of Stockholm, SE) discuss
deterioration of a 17th century warship, the authors making the
following points:

1) The seventeenth-century Swedish warship, Vasa, was recovered
in good condition after 333 years in the cold brackish water of
Stockholm harbor. After extensive treatment to stabilize and dry
the ship's timbers(1), the ship has been on display in the Vasa
Museum since 1990. However, high acidity and a rapid spread of
sulfate salts were recently observed on many wooden surfaces(2),
which threaten the continued preservation of the Vasa.

2) The Vasa sank in Stockholm harbor on her maiden voyage in
1628, and was salvaged in 1961. The massive oak beams were
seemingly in good condition after 333 years at 32 m depth.
Marine burial occasionally deposits wooden objects in near
anoxic environments that arrest natural decay. This favors
sulfate-reducing bacteria producing hydrogen sulfide in an
environment inhospitable to most wood-metabolizing microbes(3).
In such conditions, slow biodegradation of waterlogged wood
takes place mainly by heterotrophic "erosion" bacteria(4),
leaving a weak water-filled skeleton of cell lamellae. Before
the wood can be dried, the internal water must be replaced with
a non-volatile material to prevent shrinkage of the artefact.

3) The authors report that, in addition to concentrations of
sulfate mostly on the surface of oak beams, elemental sulfur has
accumulated within the beams (0.2-4 per cent by mass), and also
sulfur compounds of intermediate oxidation states exist. The
overall quantity of elemental sulfur could produce up to 5000 kg
of sulfuric acid when fully oxidized. The authors suggest that
the oxidation of the reduced sulfur -- which probably originated
from the penetration of hydrogen sulfide into the timbers as
they were exposed to the anoxic water -- is being catalyzed by
iron species released from the completely corroded original iron
bolts, as well as from those inserted after salvage. Treatments
to arrest acid wood hydrolysis of the Vasa and other wooden
marine-archaeological artefacts should therefore focus on the
removal of sulfur and iron compounds.

References (abridged):

1. Hafors, B. Conservation of the Swedish Warship Vasa from 1628
1-180 (Vasa Museum, Stockholm, Sweden, 2001).

2. Sandstrom, M., Jalilehvand, F., Persson, I., Gelius, U. &
Frank, P. in Proc. 8th ICOM-CC WOAM Conference (ed. Hoffmann,
P.) (ICOM, Committee for Conservation, Working Group on Wet
Organic Archaeological Materials, Stockholm, in the press).

3. Peterson, C. E. in Archaeological Wood, Properties, Chemistry
and Preservation (eds Rowell, R. M. & Barbour, R. J.) 433-449
(Advances in Chemistry Series 225, American Chemical Society,
Washington DC, 1990).

4. Blanchette, R. A., Nilsson, T., Daniel, G. & Abad, A. in
Archaeological Wood, Properties, Chemistry and Preservation (eds
Rowell, R. M. & Barbour, R. J.) 141-192 (Advances in Chemistry
Series 225, American Chemical Society, Washington DC, 1990).

5. Barkman, L. in National Bureau of Standards (Spec. Publ. No.
479) 155-166 (Gaithersburg, Maryland, 1977).

Nature 2002 415:893

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

21. ON DIRECTED SMALL-WORLD NETWORKS

A.D. Sanchez et al (Institute of Physics of Cantabria, ES)
discuss small-world networks, the authors making the following
points:

1) Complex networks have recently attracted an increasing
interest among physicists, the main reason being that they seem
to be exceedingly simple model systems of complex behavior in
real world networks [1,2], including chemical reaction networks
[3], food webs [4-5], the Internet, and the World Wide Web],
metabolic and protein networks, scientific collaboration
networks, etc. The hope is that the ideas and techniques,
developed in the past fifty years in the field of statistical
physics to deal with cooperative phenomena in many body systems,
may be useful to understand emergent complex behavior in systems
outside the traditional realm of physics. In particular,
small-world networks, recently introduced by Watts and Strogatz
(1998), have been very much studied because they constitute an
interesting attempt to translate the complex topology of social,
economic, and physical networks into a simple model. Small-world
networks result from randomly replacing a fraction (p) of links
of a (d)-dimensional regular lattice with new random links. As a
result of this random rewiring, small-world networks interpolate
between the two limiting cases of a regular lattice (p = 0) and
completely random graphs (p = 1). Studies of real network data
have shown that small-world-like topologies are found in
situations as diverse as the network of movie actors'
collaboration, the electric power grid of Southern California,
the network of world airports, the acquaintance network of
Mormons, etc. [1,2].

2) In the language of social network analysis, sites are
referred to as "actors". Actors may represent individuals,
companies, airports, countries, etc., depending on the social or
economic process we are interested in. Actors are linked to one
another by a relational, social, or physical tie as, for
instance, friendship, business transactions, flight connections,
kinship, or scientific collaboration, among many others. Some of
those relational links are symmetric, in the sense that if Alice
is tied to Bob, then Bob must also be tied to Alice, as occurs,
for instance, in the authorship of scientific papers. However,
many other networks are directed and exhibit links that are
definitely asymmetric, as for instance, in the case of networks
of the import and the export of goods, World Wide Web page
links, lending transactions, food webs, cultural influences,
etc. In directed networks then, when Alice is tied to Bob, Bob
may not be linked to Alice but to someone else instead.
Asymmetric synaptic strengths have already been shown to be very
important in trying to describe the process of learning in
realistic neural network model approaches to brain function.

3) The authors report an investigation of the effect of directed
links on the behavior of a simple spin-like model evolving on a
small-world network. This model may describe for instance the
dynamics of public opinion in social influence networks. The
authors demonstrate that directed networks may lead to a highly
nontrivial phase diagram including first- and second-order phase
transitions out of equilibrium.

References (abridged):

I. D.J. Watts, Small Worlds: The Dynamics of Networks Be tween
Order and Randomness (Princeton University Press, Princeton, New
Jersey, 1999).

2. L. A. N. Amaral et al., Proc. Natl. Acad. Sci. U.S.A. 97,
11149 (2000).

3. U. Alon et al., Nature (London) 397, 168 (1999).

4. S.L. Pimm, J.H. Lawton, and J.E. Cohen, Nature (London) 350,
669 (1991).

5. R.T. Paine, Nature (London) 355, 73 (1992).

Phys. Rev. Lett. 2002 88:048701

Related Background:

RANDOM GRAPH MODELS OF SOCIAL NETWORKS

In mathematics, a "graph", in the context of the field known as
"graph theory", is a mathematical object composed of points
known as "vertices" or "nodes" and lines connecting some
(possibly empty) subset of them, known as "edges".

A "random graph", in this context, is a graph in which
properties such as the number of nodes, edges, and connections
between them are determined in some random way.

M.E. Newman et al (Columbia University, US) discuss social
networks, the authors making the following points:

1) A social network is a set of people or groups of people,
"actors" in the jargon of the field, with some pattern of
interactions or "ties" between them. Friendships among a group
of individuals, business relationships between companies, and
intermarriages between families are all examples of social
networks that have been studied in the past. Network analysis
has a long history in sociology, the literature on the topic
stretching back at least half a century to the pioneering work
of Rapoport, Harary, and others in the 1940s and 1950s.
Typically, network studies in sociology have been data-oriented,
involving empirical investigation of real-world networks, the
investigation often followed by graph theoretical analysis aimed
at determining the centrality or influence of the various actors.

2) Most recently, after a surge in interest in network structure
among mathematicians and physicists, partly as a result of
research on the Internet and on the World Wide Web, another body
of research has investigated the statistical properties of
networks and methods for modeling networks either analytically
or numerically. One important and fundamental result that has
emerged from these studies concerns the numbers of ties that
actors have to other actors, their so-called "degrees". It has
been found that in many networks, the distribution of actors'
degrees is highly skewed, with a small number of actors having
an unusually large number of ties. Simulations and analytical
work have suggested that this skewness could have an impact on
the way in which communities operate, including the way
information travels through the network and the robustness of
networks to removal of actors.

3) The authors describe some new exactly solvable models of the
structure of social networks, the models based on random graphs
with arbitrary degree distribution. The authors provide models
both for simple unipartite networks, such as acquaintance
networks, and for bipartite networks, such as affiliation
networks. The authors compare the predictions of their models to
data for a number of real-world social networks and find that in
some cases the models are in remarkable agreement with the data,
whereas in other cases the agreement is poorer, perhaps
indicating the presence of additional social structure in the
network not captured by the random graph.

Proc. Nat. Acad. Sci. 2002 99:2566

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

22. ON SOLID PHASE ORGANIC SYNTHETIC CHEMISTRY

1) To synthesize a dipeptide from two amino acids, the carboxy
group of the C-terminal amino acid and the amino group of the
N-terminal amino acid are usually protected. When R.B.
Merrifield first performed his ingenious concept of solid phase
synthesis,(1) the carboxy-terminal amino acid was attached to
the solid support via an ester linkage. The ester served two
simultaneous functions: (i) it allowed tethering of the amino
acid to the solid support, and (ii) it protected the carboxylate
function from participating in subsequent reactions. Thus, the
carboxylate, an inherent part of the target peptide, was a very
useful functionality for the application of the solid phase
synthetic method. The benzyl ester type of linkage became very
popular, and its properties, particularly acid lability and
sensitivity toward nucleophiles, have been optimized for various
synthetic tasks (for reviews, see refs 2 and 3). A similar
concept was developed for the preparation of peptide amides,
whereby the most commonly used linker is a derivatized
benzhydrylamine function.

2) Not surprisingly, solid phase synthesis did not remain
limited to peptides, and early contributions were made to its
use for general organic synthesis, particularly by Leznoff,(4,5)
Frechet, and Rapoport. Solid phase organic synthesis is
attractive from at least three perspectives: (i) it allows very
simple separation of synthetic intermediates from soluble
components of a reaction mixture by simple filtration and
washing of the resin-bound reaction product. A straightforward
consequence is the ability to use a high-boiling reaction
solvent without the need to evaporate the solvent. (ii) A high
concentration of reactants in solution facilitates driving
reactions to completion. Note that the high concentration of
reagents (obviously in excess) plays the key role rather than
the excess of reagent per se. Peptide synthesis on beaded
cellulose with substitution of 0.005 mmol/mL using a 5-fold
excess of activated amino acid did not drive the reaction to
completion (the concentration of active species was 0.025 M).
(iii) A simple repetitive process (adding reagent, mixing,
washing) allows for integration and/or automation of solid phase
synthesis.

3) When Merrifield was looking for a suitable insoluble support
for his solid phase peptide synthesis, his choice ended up as a
beaded form of copolymer of styrene and divinylbenzene. Since
then a variety of solid phase supports have been introduced, a
number of them claiming superior properties when compared to the
original Merrifield resin. However, after almost 40 years, the
copoly(styrene-1% divinylbenzene) is still the most commonly
used resin. The polymeric matrix surrounds the synthesized
compound and it behaves as a solvent. Thus, synthesis on
copoly(styrene-divinylbenzene) resembles performing the
reactions in toluene. The highly hydrophobic nature of the
polymer prompted Rapp et al (1989) to graft the polystyrene
copolymer with linear poly(ethylene glycol) chains. A new resin
termed TentaGel (Argonaut and NovaBiochem introduced later
similar resins, ArgoGel and NovaGel, respectively) gained
popularity, and better kinetics for reactions requiring polar
media was reported. However, there is no single polymer support
that favors all reactions, and the need to use polar or nonpolar
media should influence the choice of support. Until the early
1990s, solid phase organic synthesis was not widely used, and
its domains remained principally peptides, nucleic acids, and,
later, carbohydrates. The renaissance of solid phase organic
synthesis was triggered by the advent of combinatorial chemistry
techniques.

References (abridged):

1. Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149-2154

2. James, I. W. Tetrahedron 1999, 55, 4855-4946

3. Guillier, F.; Orain, D.; Bradley, M. Chem. Rev. 2000, 100,
2091-2157

4. Leznoff, C. C. Chem. Soc. Rev. Chem. Soc. Rev. 1974, 3, 65-85

5. Leznoff, C. C. Account Chem. Res. 1978, 11, 327-333

Chem. Rev. 2002 102:61

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

23. ON THE DISSOLUTION OF CELLULOSE BY IONIC LIQUIDS

In general, in this context, the term "derivatization" refers to
the process of deriving a compound from some other compound
while maintaining general structure: e.g., trichloromethane
(chloroform) is a derivative of methane.

R.P. Swatloski et al (University of Alabama, US) discuss the
dissolution of cellulose, the authors making the following
points:

1) Cellulose is the most abundant biorenewable material, with a
long and well-established technological base.(1) Derivatized
products have many important applications in the fiber, paper,
membrane, polymer, and paints industries. Cellulose consists of
polydisperse linear glucose polymer chains which form
hydrogen-bonded supramolecular structures(2); cellulose is
insoluble in water and most common organic liquids. The growing
interest to develop new cellulosic materials results from the
fact that cellulose is a renewable resource, although many of
the technologies currently used in cellulose processing are
decidedly nongreen.(3) For example, viscose rayon is prepared
from cellulose xanthate (production over 3 million tons per
year) utilizing carbon disulfide as both reagent and solvent.
Most recently, processes using more environmentally acceptable
nonderivatizing solvents (N-methylmorpholine-N-oxide and
phosphoric acid) have been commercialized. Solvents are needed
for dissolution that enable homogeneous phase reactions without
prior derivatization.(4)

2) C. Graenacher (5) first suggested in 1934 that molten
N-ethylpyridinium chloride, in the presence of
nitrogen-containing bases, could be used to dissolve cellulose;
however, this seems to have been treated as a novelty of little
practical value, since the molten salt system was at the time
somewhat esoteric and has a relatively high melting point (118
C).

3) The authors report they have examined whether other solvents
that would now be described as ionic liquids would dissolve
cellulose and, especially, whether the availability of a wide
and varied range of ionic liquids, coupled with the current
understanding of their solvent properties would allow
flexibility and control in the processing methodology, with
increased solution efficiency and reduction or elimination of
undesirable solvents. The authors report that ionic liquids can
be used as nonderivatizing solvents for cellulose. Ionic liquids
incorporating anions which are strong hydrogen bond acceptors
were most effective, especially when combined with microwave
heating, whereas ionic liquids containing "non coordinating"
anions were nonsolvents. Chloride containing ionic liquids
appear to be the most effective solvents, presumably
solubilizing cellulose through hydrogen-bonding from hydroxyl
functions to the anions of the solvent.

References (abridged):

1. Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.;
Wiley: New York, 1993; Vol. 5, p 476.

2. Finkenstadt, V. L.; Millane, R. P. Macromolecules 1998, 31,
7776-7783.

3. Johnson, D. C. In Cellulose Chemistry and its Application;
Nevell, T. P., Zeronian, S. H., Eds.; E. Horwood: Chichester,
1985; p181.

4. (a) Augustine, A. V.; Hudson, S. M.; Cuculo, J. A. In
Cellulose Sources and Exploitation; Kennedy, J. F., Philipps, G.
O., Williams, P. A., Eds.; E. Horwood: New York, 1990; p59. (b)
Dawsey, T. R. In Cellulosic Polymers, Blends and Composites;
Gilbert, R. D., Ed.; Carl Hanser Verlag: New York, 1994; p157.

5. Graenacher, C. Cellulose Solution. U.S. Patent 1,943,176,
1934.

J. Am. Chem. Soc. 2002 124:4974

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

24. ON LIGHT-POWERED MOLECULAR MACHINES

T. Hugel et al (Ludwig-Maximilians University, DE) discuss
molecular machines, the authors making the following points:

1) Nanomechanical devices or molecular machines will, for a
broad range of applications, most likely be powered by light or
other kinds of electromagnetic radiation (1-4). The dominant
reasons are ease of addressability, picosecond reaction times to
external stimuli, and compatibility with a broad range of
ambient substances, such as solvents, electrolytes, gases, or
vacuum. One of the key challenges, not only in the development
phase but also in operation, is the need to interface such
nanometer-sized or molecular devices with the macroscopic world.
Single-molecule force spectroscopy by atomic force microscope
(AFM) techniques has in the past proven to be an extremely
successful strategy (5). Successful attempts to use an AFM tip
to guide the activity of enzymes have paved the road toward a
molecular machine tool.

2) The authors report they have combined single-molecule
mechanics with optics to excite an ensemble of molecules and
mechanically select an individual molecule from this ensemble.
As the photoactive system, they used a polymer of azobenzene
units. This well-studied chromophore, which can be reversibly
switched at two different wavelengths between an extended trans
and a shorter cis configuration, has been the basis for many
experiments, such as light-driven ion transport through
membranes. It has frequently been used in synthetic
photoresponsive systems, regulating the geometry and function of
biomolecules, organic materials, and supramolecular complexes.
Photomechanical effects have been demonstrated for azobenzene
polymers in bulk. The potential energy landscape of azobenzene
has been determined in ab initio calculations and experimentally
probed by spectroscopy. The conformational flexibility required
for reversible optical switching is retained in a polypeptide
backbone. To ensure stable attachment, the polymer end groups
were covalently coupled to both the AFM tip and a supporting
glass slide by heterobifunctional chemistry.

3) In summary: Light-powered molecular machines are conjectured
to be essential constituents of future nanoscale devices. As a
model for such systems, the authors have synthesized a polymer
of bistable photosensitive azobenzenes. Individual polymers were
investigated by single-molecule force spectroscopy in
combination with optical excitation in total internal
reflection. The authors report they were able to optically
lengthen and contract individual polymers by switching the azo
groups between their trans and cis configurations. The polymer
was found to contract against an external force acting along the
polymer backbone, thus delivering mechanical work. As a proof of
principle, the polymer was operated in a periodic mode,
demonstrating for the first time optomechanical energy
conversion in a single-molecule device.

References (abridged):

1. V. Balzani, A. Credi, F. M. Raymo, J. F. Stoddart, Angew.
Chem. Int. Ed. 39, 3348 (2000)

2. B. L. Feringa, R. A. van Delden, N. Koumura, E. M. Geertsema,
Chem. Rev. 100, 1789 (2000)

3. J. P. Collin, P. Gavi¤a, V. Heitz, J. P. Sauvage, Eur. J.
Inorg. Chem. 1998, 1 (1998)

4. J. M. Lehn, Supramolecular Chemistry: Concepts and
Perspectives (Wiley-VCH, Weinheim, Germany, 1995)

5. G. U. Lee, D. A. Kidwell, R. J. Colton, Langmuir 10, 354
(1994)

Science 2002 296:1103

ScienceWeek http://www.scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

25. IN FOCUS: ON POWER-LAW DEGREE DISTRIBUTION NETWORKS

Albert-Laszlo Barabasi (University of Notre Dame, US) makes the
following points:

1) The striking visual and structural differences between a
random network and one described by a power-law degree
distribution are best seen by comparing a U.S. roadmap with an
airline routing map. On the roadmap cities are the nodes and the
highways connecting them the links. This is a fairly uniform
network: Each major city has at least one link to the highway
system, and there are no cities served by hundreds of highways.
Thus most nodes are fairly similar, with roughly the same number
of links. ... Such uniformity is an inherent property of random
networks with a peaked degree distribution.

2) The airline routing map differs drastically from the roadmap.
The nodes of this network are airports connected by direct
flights between them. Inspecting the maps displayed in the
glossy flight magazines placed on the back of each airplane
seat, we cannot fail to notice a few hubs, such as Chicago,
Dallas, Denver, Atlanta, and New York, from which flights depart
to almost all other U.S. airports. The vast majority of airports
are tiny, appearing as nodes with at most a few links connecting
them to one or several hubs. Thus, in contrast to the highway
map, where most nodes are equivalent, on the airline map a few
hubs connect hundreds of small airports.

3) A similar unevenness characterizes networks with power-law
degree distribution. Power laws mathematically formulate the
fact that in most real networks the majority of nodes have only
a few links and that these numerous tiny nodes coexist with a
few big hubs, nodes with an anomalously high number of links.
The few links connecting the smaller nodes to each other are not
sufficient to ensure that the network is fully connected. This
function is secured by the relatively rare hubs that keep real
networks from falling apart.

4) In a random network the peak of the distribution implies that
the vast majority of nodes have the same number of links and
that nodes deviating from the average are extremely rare.
Therefore, a random network has a characteristic scale in its
node connectivity, embodied by the average node and fixed by the
peak of the degree distribution. In contrast, the absence of a
peak in a power-law degree distribution implies that in a real
network there is no such thing as a characteristic node. We see
a continuous hierarchy of nodes, spanning from rare hubs to the
numerous tiny nodes. The largest hub is closely followed by two
or three somewhat smaller hubs, followed by dozens that are even
smaller, and so on, eventually arriving at the numerous small
nodes.

5) The power law distribution thus forces us to abandon the idea
of a scale, or a characteristic node. In a continuous hierarchy
there is no single node which we could pick out and claim to be
characteristic of all the nodes. There is no intrinsic scale in
these networks.

Albert-Laszlo Barabasi: Linked: The New Science of Networks
(Perseus Publishing, Cambridge MA 2002, p.69)
Source information at Amazon.Com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

NOTICES

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

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

ScienceWeek copyright extends only to material originated by
ScienceWeek. Other copyrights may obtain for other material.

CHANGE OF EMAIL ADDRESS:

If at any time you need to change the Email address at which you
receive SW, please send the information to:
request@scienceweek.com

SCIENCE-WEEK SUBSCRIPTIONS:

Information concerning subscriptions is available at:
http://www.scienceweek.com/subinfo.htm

We welcome comments, suggestions, and criticisms from our
subscribers. Public letters relevant to any report are also
welcome. Editorial contact: editors@scienceweek.com

Editor/Publisher: Dan Agin

Managing Editor: Claire Haller

Associate Editor: Joan Oliner

Copyright (c) 1997-2002 SCIENCE-WEEK

All Rights Reserved

US Library of Congress ISSN 1529-1472

---------------------------------------------

ScienceWeek/Spectrum Press Inc.

3023 N. Clark Street #109

Chicago, 60657-5205 IL, USA.

---------------------------------------------

-----end file