ScienceWeek

ScienceWeek - May 10, 2002 Vol. 6 Number 19

An Online Research Digest Published Weekly Since 1997

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This fright, this night of the mind, must be dispelled not by
the rays of the sun, nor day's bright spears, but by the face of
nature and her laws.
-- Lucretius (95-55 B.C.)

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Top Graphic: Composition VIII -- Wassily Kandinsky (1866-1944)

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Section 1

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

[(*) = includes background reports from ScienceWeek] [Subheads
under each report (e.g., 2a) provide supplementary material from
other archives related to main report.]

Basic Sciences:

1. On Genomes and the Evolution of Multicellular Animals
1a. The Origins and Relationships of the Metazoa

2. Molecular Chaperones and the Folding of Proteins 

3. On the Neural Basis of a Pavlovian Conditioned Response
3a. Biography of Ivan Pavlov (1849-1936)

4. Functional Role of Asymmetric Lipid Distribution in Cell
Membranes (*) 

5. Nucleosomes and DNA Packing 

6. Biological Systems in Antarctic Sea Ice 

7. On the Dynamic Glass Transition 

8. A Laboratory Analogue of the Black Hole Event Horizon 

9. On the Predictability of Earthquakes (*) 

10. Astrophysics: On Local and Distant Galaxies 

11. On Binary Water-Surfactant Systems 

12. Global Asymmetry of the Planet Mars
12a. The Planet Mars: A History of Observation and Discovery

Praxis:

13. On Schistosomiasis
13a. Schistosomiasis: A Review 

14. Analysis of DNA Microarrays by Rule-Based Computation

15. Patterns of Adult Medication Use in the US

16. On Tumor Oximetry 

17. Cooperativity in Drug-DNA Recognition 

18. Complexity of the Human Genome and Biomedical Research (*) 

19. On Resonance-Induced Pacemakers 

20. Diffusion in Glasses and Supercooled Liquids 

21. On the Problem of Predictability in Solid-State Synthesis
21a. Notes on Solid-State Reactions

22. Controlling Crystal Morphology (*) 

23. Shape Control of Macromolecules 

24. Surface Phase Transition Temperatures 

Miscellany:

25. In Focus: On Magnetism in Solids 

26. ScienceWeek Notices and Subscription Information

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Section 2

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1. ON GENOMES AND THE EVOLUTION OF MULTICELLULAR ANIMALS

The term "choanoflagellates" refers to an order
(Choanoflagellida) of mostly unicellular and often stalked
zooflagellates containing approximately 140 species found in
aquatic habitats and characterized by a single emergent
flagellum surrounded by a funnel-like collar of tentacles. These
organisms feed on bacteria extracted by the tentacles from
currents set up by the flagellum.

The term "cnidarian" refers to a subphylum of coelenterates
containing hydroids, jellyfish, sea anemones, and corals.

N. King and S.B. Carroll (University of Wisconsin, US) discuss
the evolution of multicellular animals, the authors making the
following points:

1) A pivotal transition in the history of life was the evolution
of multicellular animals (metazoans) from a unicellular
protozoan ancestor. The genetic and developmental events
involved in the origin of metazoan multicellularity remain
obscure. In particular, it is not known whether proteins
involved in animal cell-cell interactions arose before (and may
have contributed to) the origin of metazoa. Although DNA from
the ancestor to metazoa cannot be examined directly, the
contents of that genome may be inferred by comparing genomes of
extant metazoa to those of their nearest relatives. Those genes
that are shared in certain groups and not others may reflect the
assembly of the "genetic toolkit" during metazoan evolution.
Genes restricted to animals and their closest relatives may have
played important roles in the evolution of unique modes of cell
communication and adhesion that characterize metazoan biology.

2) Comparisons of worm and fly genomes with that of a fungus
(Saccharomyces cerevisiae) have revealed genes for numerous
signaling and extracellular matrix molecules that are
potentially unique to the metazoa. However, the long
evolutionary history separating animals from fungi and the
profound differences in their cell biology suggest that genes
important for animal evolution may have arisen after the
divergence of the two lineages. Furthermore, the diversity of
signaling and adhesion molecules in the most basal animals,
sponges and cnidarians, indicates that some of these protein
families may have arisen before the origin and diversification
of metazoa. A better picture of the evolution of early animal
genomes will require the identification of phylogenetically and
biologically appropriate species for comparison with animals.

3)  The choanoflagellates have long been suspected to be closer
relatives of animals than are fungi, the closest outgroup of
animals for which comparative genomic information is available.
The authors report that analyses of four conserved proteins from
a unicellular choanoflagellate, Monosiga brevicollis, provide
robust support for a close relationship between
choanoflagellates and metazoa, suggesting that comparison of the
complement of expressed genes from choanoflagellates and animals
may be informative concerning the early evolution of metazoan
genomes.

References (abridged):

1. Aravind, L. & Subramanian, G. (1999) Curr. Opin. Genet. Dev.
9, 688-694

2. Chervitz, S. A. , Aravind, L. , Sherlock, G. , Ball, C. A. ,
Koonin, E. V. , Dwight, S. S. , Harris, M. A. , Dolinski, K. ,
Mohr, S. , Smith, T. , et al. (1998) Science 282, 2022-2028

3. Rubin, G. M. , Yandell, M. D. , Wortman, J. R. , Gabor
Miklos, G. L. , Nelson, C. R. , Hariharan, I. K. , Fortini, M.
E. , Li, P. W. , Apweiler, R. , Fleischmann, W. , et al. (2000)
Science 287, 2204-2215

4. Exposito, J. Y. & Garrone, R. (1990) Proc. Nat. Acad. Sci.
87, 6669-6673

5. Brower, D. L. , Brower, S. M. , Hayward, D. C. & Ball, E. E.
(1997) Proc. Natl. Acad. Sci. USA 94, 9182-9187

Proc. Nat. Acad. Sci. 2001 98:15032

Also:

Ex Link: The Origins and Relationships of the Metazoa

ScienceWeek http://www.scienceweek.com

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2. MOLECULAR CHAPERONES AND THE FOLDING OF PROTEINS

F.U. Hartl and M. Hayer-Hartl (Max Planck Institute for
Biochemistry Martinsried, DE) discuss molecular chaperones, the
authors making the following points:

1) To become functionally active, newly synthesized protein
chains must fold to unique three-dimensional structures. How
this is accomplished remains a fundamental problem in biology.
Although it is firmly established from refolding experiments in
vitro that the native fold of a protein is encoded in its amino
acid sequence, protein folding inside cells is not generally a
spontaneous process. Evidence accumulated over the last decade
indicates that many newly synthesized proteins require a complex
cellular machinery of "molecular chaperones" in addition to the
input of metabolic energy to reach their native states
efficiently. The various chaperone factors protect nonnative
protein chains from misfolding and aggregation, but do not
contribute conformational information to the folding process.

2) Spontaneous refolding in vitro is generally efficient for
small, single-domain proteins that bury exposed hydrophobic
amino acid residues rapidly (within milliseconds) upon
initiation of folding. In contrast, larger proteins composed of
multiple domains often refold inefficiently, owing to the
formation of partially folded intermediates, including misfolded
states, that tend to aggregate. Misfolding originates from
interactions between regions of the folding polypeptide chain
that are separate in the native protein and that may be stable
enough to prevent folding from proceeding at a biologically
relevant time scale. These nonnative states, though compact in
shape, often expose hydrophobic amino acid residues and segments
of unstructured polypeptide backbone to the solvent. They
readily self-associate into disordered complexes, driven by
hydrophobic forces and interchain hydrogen bonding. This
aggregation process irreversibly removes proteins from their
productive folding pathways, and must be prevented in vivo by
molecular chaperones. A certain level of protein aggregation
does occur in cells despite the presence of an exclusive
chaperone machinery and, in special cases, can lead to the
formation of structured, fibrillar aggregates, known as
"amyloid", that are associated with diseases such as Alzheimer's
or Huntington's disease. Compared to refolding in dilute
solution, the tendency of nonnative states to aggregate in the
cell is expected to be sharply increased as a result of the high
local concentration of nascent chains newly synthesized proteins
in polyribosomes and the added effect of macromolecular crowding.

References (abridged):

1. C. Dobson and M. Karplus, Curr. Opin. Struct. Biol. 9, 92
(1999)

2. R. J. Ellis and S. M. Hemmingsen, Trends Biochem. Sci. 14,
339 (1989)

3. M.-J. Gething and J. Sambrook, Nature 355, 33 (1992)

4. F. U. Hartl, Nature 381, 571 (1996)

5. J. Frydman, Annu. Rev. Biochem. 70, 603 (2001)

Science 2002 295:1852

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3. ON THE NEURAL BASIS OF A PAVLOVIAN CONDITIONED RESPONSE

The cerebellum is relatively large brain appendage that
coordinates sensory input with muscular responses, and in
mammals is located just below and behind the cerebral
hemispheres and above the midbrain (medulla oblongata). Like the
cerebrum, the cerebellum has a convoluted cortex. Of several
medullary relay nuclei that project to the cerebellum, the
largest is the nucleus called the "inferior olive". In this
context, a "nucleus" is a cluster of nerve cells.

The term "pons" refers to a portion of the mammalian brain lying
above the medulla oblongata and below the cerebellum and the
cavity of the fourth ventricle. The pons is a broad,
horseshoe-shaped mass of transverse nerve fibers that connect
the medulla with the cerebellum. It is also the point of origin
or termination for four of the cranial nerves that transfer
sensory information and motor impulses to and from the facial
region and the brain.

In this context, the term "Purkinje cells" refers to large
principal output (projection) neurons of the cerebellum that
have as their defining characteristic an elaborate arborization
of dendrites (i.e., an elaborate local input system).

In this context, "climbing fibers" are fibers in the cerebellar
cortex that make synapses with Purkinje cell dendrites. "Mossy
fibers" are highly branched nerve fibers in the cerebellar
cortex that make connection to neurons known as "granule cells".
The "interpositus nucleus" is a collective term for an
anatomical region of the cerebellum.

Shigeru Kitazawa (National Institute for Advanced Industrial
Science and Technology Tsukuba, JP) discusses pavlovian
conditioning, the author making the following points:

1) The classic experiments of Ivan Pavlov (1849-1936)
demonstrated that when a dog is repeatedly fed after a neutral
tone is sounded, the animal soon learns to salivate when it
hears the tone. Among other pavlovian responses, one that is
commonly used in laboratory studies is the "eye-blink" response:
a brief shock near the eye causes "innate" defensive blinking.
When a brief tone is repeatedly paired with the shock, the tone
comes to elicit a "conditioned" blinking response that begins
just before and peaks at approximately the time that the shock
would be expected.

2) Several brain regions, which are either within or connected
to the cerebellum, are required to learn the conditioned
eye-blink response. A shock elicits defensive blinking by
setting off electrical impulses through simple neuronal circuits
(known as "reflex arcs") in the brain stem. By contrast, a tone
causes conditioned blinking by sequentially activating the pons,
mossy fibers, and interpositus nucleus, among other parts of the
brain.

3) Before the conditioned response has been "acquired", impulses
set off by the tone are blocked at the interpositus nucleus by
so-called "Purkinje cells". When the tone and shock are
combined, electrical impulses are conveyed in parallel to the
Purkinje cells, the tone by way of mossy fibers, granule cells
and parallel fibers, and the shock via the inferior olive and
climbing fibers. The joint activation of parallel fibers and
climbing fibers induces long-term depression — which is thought
to involve long-lasting molecular changes — of the connections
(synapses) between the parallel fibers and Purkinje cells. This
reduces the activity of the Purkinje cells. Thus, when the tone
and shock are repeatedly paired, the activity of the Purkinje
cells is progressively reduced, and so too is the inhibition of
the interpositus nucleus by the Purkinje cells. This means that
the tone can now act via the interpositus nucleus to evoke
conditioned blinking.

4) However, if learning such an association is important,
forgetting it when necessary is also important. Thus, if the
tone is sounded without a shock, the rate and amplitude of
blinking gradually decrease until the tone no longer evokes a
response. This process is known as "extinction", and Medina et
al (2002) have recently demonstrated that extinction is not a
passive process of "forgetting", but rather an active
"unlearning" process that is driven by inhibition of climbing
fibers.

References (abridged):

1. Medina, J. F., Nores, W. L. & Mauk, M. D. Nature 416, 330-333
(2002).

2. Kim, J. J. & Thompson, R. F. Trends Neurosci. 20, 177-181
(1997).

3. Mauk, M. D., Garcia, K. S., Medina, J. F. & Steele, P. M.
Neuron 20, 359-362 (1998).

4. Ito, M. Physiol. Rev. 81, 1143-1195 (2001).

5. Kim, J. J., Krupa, D. J. & Thompson, R. F. Science 279,
570-573 (1998).

Nature 2002 416:270

Also:

Ex Link: Biography of Ivan Pavlov (1849-1936)

ScienceWeek http://www.scienceweek.com

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4. FUNCTIONAL ROLE OF ASYMMETRIC LIPID DISTRIBUTION IN CELL
MEMBRANES

S. Manno et al (Tokyo Women's Medical University, JP) discuss
lipids in cell membranes, the authors making the following
points:

1) Asymmetric distribution of phospholipids is ubiquitous in the
plasma membranes of many eukaryotic cells. The majority of the
aminophospholipids are located in the inner leaflet whereas the
cholinephospholipids are localized predominantly in the outer
leaflet. Several functional roles for asymmetric phospholipid
distribution in plasma membranes have been suggested. Disruption
of lipid asymmetry creates a procoagulant surface on platelets
and serves as a trigger for macrophage recognition of apoptotic
cells. Furthermore, the dynamic process of phospholipid
translocation regulates important cellular events such as
membrane budding and endocytosis.

[Graphic: Architecture of the Cell Membrane]

2) The authors report they used the red cell membrane as a model
system to explore the contribution of phospholipid asymmetry to
the maintenance of membrane mechanical properties. They prepared
two different types of membranes in terms of their phospholipid
distribution, one in which phospholipids were scrambled and the
other in which the asymmetric distribution of phospholipids was
maintained, and the authors quantitated their mechanical
properties. The authors report that maintenance of asymmetric
distribution of phospholipids resulted in improved membrane
mechanical stability. The greater difficulty in extracting the
spectrin-actin complex at low-ionic strength from the membranes
with asymmetric phospholipid distribution further suggested the
involvement of interactions between aminophospholipids in the
inner leaflet and skeletal proteins in modulating mechanical
stability of the red cell membrane. The authors suggest these
findings demonstrate a functional role of lipid asymmetry in
regulating membrane material properties.

References (abridged):

1. Devaux, P.F. (1991) Biochemistry 30, 1163-1173

2. Williamson, P. & Schlegel, R. A. (1994) Mol. Membr. Biol. 11,
99-216

3. Tang, X. , Halleck, M. S. , Schlegel, R. A. & Williamson, P.
(1996) Science 272, 1495-1497

4. Devaux, P.F. (1992) Annu. Rev. Biophys. Biomol. Struct. 21,
417-439

5. Zwaal, R. F. A. & Schroit, A. J. (1997) Blood 89, 1121-1132

Proc. Nat. Acad. Sci. 2002 99:1943

Related Background:

A SUPERLATTICE MODEL FOR RED CELL MEMBRANE PHOSPHOLIPIDS

The biological phospholipids, which are essentially long-chain
fatty acids with a phosphate polar group at one end, are among
the most important chemical substances in biological systems,
responsible in various ways for the individualization of cells
and the compartmentalization of the interior of cells as a
result of the ability of phospholipids to form self-organizing
layers in surfaces, spheres, cylinders, and so on. Despite
recent progress in understanding the structure and function of
biological membranes, certain crucial issues remain unresolved.
For example, it is not well understood how the particular lipid
composition of cell membranes arise and are maintained. There is
some evidence that the components of bilayers have a tendency to
acquire regular superlattice-like lateral distributions, and a
consequence of such behavior would be that a number of
predictable critical compositions corresponding to optimal
lateral arrangements of the components occur.

... ... Virtanen et al (3 installations, US FI) report a study
of the possibility that such critical compositions play a role
in regulating lipid compositions of natural membranes. The
authors have compared the already known phospholipid
compositions of the erythrocyte (red cell) membrane from various
mammals with the critical compositions predicted by the
superlattice model. The erythrocyte membrane was selected
because its composition has been studied in considerable detail,
because it may be close to compositional equilibrium, and
because it is commonly considered as a model of mammalian cell
membranes. The authors report a highly significant agreement
between the experimental and predicted values of membrane
phospholipid compositions, thus supporting the involvement of
superlattice formation in the regulation of such compositions in
the erythrocyte membrane.

Proc. Nat. Acad. Sci. 1998 95:4964

Related Background:

ELECTRIC FIELD-INDUCED DEMIXING IN LIPID BILAYER MEMBRANES In
this report, the term "critical demixing" refers to the
formation of lateral concentration gradients in a
two-dimensional system at or near the critical point for the
system -- the thermodynamic state variable point at which the
system is not phase distinguishable. A "bilayer" membrane is a
membrane consisting of two contiguous monomolecular layers, and
such layers, involving lipid molecules with polar groups, are
important in biological systems. ... ... Groves et al (3 authors
at Stanford University, US) report a method to study critical
demixing in bilayer membranes by using an electric field applied
tangent to the plane of a confined patch of a supported lipid
bilayer, and provide a thermodynamic model of the system to
analyze the results. The steady-state distribution of lipids
under the influence of an electric field is very sensitive to
demixing effects, even at temperatures well above the critical
temperature for spontaneous phase separation. The authors
suggest this may have significant consequences for organization
and structural changes in natural cell membranes.

Proc. Nat. Acad. Sci. 3 Feb 98

Related Background:

(from a SCIENCEWEEK Focus Report 8.22.97)

... The idea of the protein-lipid bilayer as the basis of
biological membranes developed as the consensus model in the
1950s when the first electron micrographs of cell membranes
became available. As we will see, the consensus model has been
elaborated since then, but first let us consider the protein-
lipid bilayer membrane in its simplest form.

One of the essential aspects of this sort of bilayer is due to
the chemical geometry of its lipid constituents. Most of these
lipid constituents are long chain fatty acids whose polar groups
are the acid end of the molecule. A typical membrane fatty acid,
for example, may have 16 carbon atoms forming the backbone of
each of two tails, and a phosphate group as the main entity at
the polar end. The backbones are hydrocarbon backbones not
essentially different from the hydrocarbon backbones of
molecules that form oils and waxes, and as we have seen in a
previous Focus Report, there are important Van der Waals forces
acting to couple these hydrocarbon chains together. Water
molecules cannot dissolve this coupling, since the interaction
of water molecules with these hydrocarbon chains is not strong
enough. So in the absence of any solvent (or heat) to dissociate
them, the hydrocarbon chains tend to associate with each other.
Because of steric and other considerations, whether these chains
are saturated or unsaturated (containing double bonds)
significantly affects their Van der Waals association, and as
expected, their melting points. Molecules such as long-chain
fatty acids, which have one region (in this instance, the polar
end) with a high affinity for aqueous solvents, and another
region (in this instance, the hydrocarbon tails) with a high
affinity for non- aqueous solvents, are called amphiphiles, and
one question which is immediately suggested is what happens when
we dump a batch of these molecules into one or the other type of
solvent? Well, if we consider what we have said here and in
previous reports, we can more or less deduce what will happen
with some confidence that experimental observations will confirm
our deductions. In the first place, if we dump a batch of fatty
acid molecules into a non-aqueous solvent such as benzene and
apply the principle that the entire system benzene plus fatty
acids must attempt to rearrange itself to maximize all possible
interaction energies, then what we would expect is the fatty
acid molecules will agglomerate, polar groups interacting with
each other in exclusion, and hydrocarbon tails interacting both
with each other and with benzene molecules. There are various
possible structures that can accomplish this maximization of
interaction energies, sheets, spheres, and so on, all on a
micro-scale involving relatively small numbers of molecules, and
that is precisely what experimental observations confirm. In
other words, these systems tend to be self-organizing into small
domains of molecules such that the possible interaction energies
can be maximized. In the simplest case, that of a simple sphere
(called a micelle), the polar groups in this benzene-fatty acid
system will be at the center of the spheres and the hydrocarbon
tails outward to interact with the benzene molecules. And if we
dump our batch of fatty acid molecules into water, the same
principles apply, and in this case we can expect to obtain
micelles with polar groups outward to interact with water, and
hydrocarbon tails inward to interact with themselves. Another
possible type of arrangement is called a vesicle, a larger
spherical entity, with some of the solvent actually inside the
sphere, and with the wall of the sphere consisting of a double
layer of fatty acid molecules -- again, everything arranged so
as to maximize the possible interaction energies for the given
conditions and entities involved. And the principles are no
different for the organization of the entities in layers:
monolayers, multilayers, and multilayers called membranes. The
basis, then, for the structural integrity of the biological cell
membrane is the fact that its lipid molecules are amphiphiles
consisting of a polar, hydrophilic heads and nonpolar oleophilic
fatty acid chains. One interesting consideration is that in many
aspects the biological cell membrane resembles the membranes of
soap bubbles. Soap consists of various types of long chain fatty
acids, and the cleaning action of soaps depends on their ability
to sequester oil soluble dirt into the oleophilic interiors of
their little micelles. The exterior polar surface of the soap
micelle interacts strongly with water, is therefore soluble in
water, and the soap micelle plus its dirt baggage is carried
away. The dirt has, in essence, been solubilized by soap
molecules constructing microscopic oil phases. All of this is
possible because of the self-organizing tendency of the
amphiphile soap molecules, and when soap bubbles are produced it
is that same self-organizing tendency which is responsible for
the special surface of the soap bubble and its stability. As in
biological cells, this special surface of the soap bubble is
about 10 nanometers in thickness, enough for a bimolecular
layer. In the 1930s, when many membrane biologists were studying
surface active substances such as soaps and their films and
bubbles, they were often derided by their biology colleagues for
working with soap bubbles rather than living systems. But, as
often happens in science, the people doing the deriding were
wrong: those years of careful investigas tion of the physical
chemistry of biological surfactants by membrane biologists laid
the foundations for the understanding of the structure of
biological cell membranes that came decades later...

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5. ON NUCLEOSOMES AND DNA PACKING

In eukaryotic chromosomes, approximately every 200 nucleotides,
the DNA double helix is coiled around a complex of 8 histone
proteins, the entire assembly having the appearance of beads on
a string. The beads (nucleosomes) are in turn supercoiled into a
solenoid structure, and the entire complex of the eukaryotic
chromosome is called "chromatin". The small histone proteins are
basic (as opposed to acidic) proteins, and they are essential in
forming nucleosomes. Chemically, histones are single polypeptide
chains, molecular mass 11 to 21 kilodaltons, 25 percent lysine
and arginine amino acids.

B.D. Brower-Toland et al (Cornell University, US) discuss
nucleosomes, the authors making the following points:

1) Nucleosomes are the fundamental organizational unit of the
eukaryotic genome, occurring on average every 200 base pairs.
The foundation of the nucleosome is the nucleosome core
particle, consisting of 147 base pairs of DNA wrapped 1.65 times
around an octamer of histone proteins. The nuclesome core
particle must be a stable and yet dynamic structure, both
maintaining eukaryotic DNA in a condensed state and also
permitting regulated access to genetic information contained
therein. Equilibrium accessibility of DNA in the nucleosome core
particle has been demonstrated by using restriction enzyme
accessibility assays. As visualized by cryoelectron microscopy,
variability in the amount of DNA associated with the histone
octamer and in the angle of exit and entry of DNA from the
nucleosome core particle are also consistent with spontaneous
peeling of DNA ends from the octamer surface. Spontaneous
peeling presents a means by which the transcriptional apparatus
might invade nucleosomal DNA, especially if this process were
facilitated by force-generating molecular motors and
destabilizing covalent histone modifications.

2) Single-molecule mechanical manipulation techniques offer a
direct approach to the investigation of the forces and
displacements required for enzymatic access to nucleosome-bound
DNA. These techniques already have provided insights into the
higher-order structure of chromatin fibers and the kinetics of
fiber assembly. However, the resolution of these studies has not
permitted observations of the interactions within individual
nucleosomes.

3) The authors report that the dynamic structure of individual
nucleosomes was examined by stretching nucleosomal arrays with a
feedback-enhanced optical trap. Forced disassembly of each
nucleosome occurred in three stages. Analysis of the data using
a simple worm-like chain model yields 76 base pairs of DNA
released from the histone core at low stretching force.
Subsequently, 80 base pairs are released at higher forces in two
stages: full extension of DNA with histones bound, followed by
detachment of histones. When arrays were relaxed before the
dissociated state was reached, nucleosomes were able to
reassemble and to repeat the disassembly process. Kinetic
parameters for nucleosome disassembly were also determined.

References (abridged):

1. Kornberg, R. & Thomas, J. (1974) Science 184, 865-868

2. Luger, K. , Mader, A. , Richmond, R. , Sargent, D. &
Richmond, T. (1997) Nature (London) 389, 251-260

3. Anderson, J. & Widom, J. (2000) J. Mol. Biol. 296, 79-987

4. Furrer, P. , Bednar, J. , Dubochet, J. , Hamiche, A. &
Prunell, A. (1995) J. Struct. Biol. 114, 177-183

5. Cui, Y. & Bustamante, C. (2000) Proc. Natl. Acad. Sci. USA
97, 27-132

Proc. Nat. Acad. Sci. 2002 99:1960

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6. ON BIOLOGICAL SYSTEMS IN ANTARCTIC SEA ICE

D.N. Thomas and G.S. Dieckmann (University of Wales-Bangor, UK)
discuss Antarctic sea ice, the authors making the following
points:

1) Sea ice is an ephemeral feature of polar regions, but also of
the Baltic, Caspian, and Okhotsk Seas. At its maximum, it covers
13 percent of the Earth's surface area, making it one of the
major biomes on the planet, similar in terms of area to that of
deserts and tundra. The largest expanse of sea ice occurs in the
Southern Ocean, where during winter 20 million square kilometers
are blanketed by an ice cover approximately 1 meter thick.
Unlike freshwater ice, frozen seawater forms a semisolid matrix
permeated by a network of channels and pores. These vary in size
from a few micrometers to millimeters and are filled with brine
formed from expelled salts as the ice crystals freeze together.
It is within this labyrinth that the sea-ice organisms live.

2) Sea ice is dominated by strong gradients in temperature,
salinity, space, and light. These properties and the morphology
of the brine channel system are highly variable, being
ultimately governed by air temperature and snow cover. Large
seasonal and even diurnal differences in ice properties occur.
Small-scale variations in ice morphology are compounded by
rafting of ice floes and deformation, which impart a tremendous
spatial heterogeneity to any sea-ice zone, even within a single
floe.

3) Many planktonic organisms, including viruses, bacteria,
algae, protists, flatworms, and small crustaceans, stick to, or
are caught between, ice crystals as they rise through the water
when surface waters freeze in autumn. Subsequently, as the ice
grows and consolidates, the organisms become trapped within the
brine channels. Hence, a diverse group of organisms is almost
instantaneously confined to a new habitat that is quite
different from the one from which they were recruited. The most
conspicuous organisms in the ice are pennate diatoms
(unicellular photosynthetic microalgae), which reach such
concentrations that their photosynthetic pigments discolor the
ice brown. Diatom standing stocks up to 1000 micrograms of
chlorophyll per liter have been measured in sea ice, which
compare with typical values of 0 to 5 micrograms of chlorophyll
per liter for surface waters in the Southern Ocean.

4) The authors conclude: Survival in sea ice conditions requires
a complex suite of physiological and metabolic adaptations, but
sea-ice organisms thrive in the ice, and their prolific growth
ensures they play a fundamental role in polar ecosystems. Apart
from their ecological importance, the bacterial and algae
species found in sea ice have become the focus for novel
biotechnology, as well as being considered proxies for possible
life forms on ice-covered extraterrestrial bodies.

References (abridged):

1. C. L. Parkinson, P. Gloersen, in Atlas of Satellite
Observations Related to Global Change, R. J. Gurney, J. -L.
Foster, and C. L. Parkinson, Eds. (Cambridge Univ. Press,
Cambridge, 1993).

2. M. P. Lizotte, Am. Zool. 41, 57 (2001)

3. H. Eicken, Polar Biol. 12, 3 (1992)

4. M. Gleitz, et al., Mar. Chem. 51, 81 (1995)

5. A. C. Palmisano, D. L. Garrison, in Antarctic Microbiology,
E. I. Friedman, Ed. (Wiley-Liss, New York, 1993), pp. 167-218.

Science 2002 295:641

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7. ON THE DYNAMIC GLASS TRANSITION

T.S. Grigera et al (University of Rome, IT) discuss the dynamic
glass transition, the authors making the following points:

1) Despite a large number of investigations, there is still much
to understand about the dynamic glass transition in supercooled
liquids. The basic problem is that, strictly speaking, there is
no dynamic transition at all. In systems known as fragile
liquids, experiment reveals a sharp rise of the viscosity in a
very narrow interval of temperature upon cooling. The shear
relaxation time increases by several orders of magnitude within
a few degrees, and it becomes impossible to perform an
equilibrium experiment. Nevertheless, sharp as this behavior may
be, it is not a genuine dynamic singularity. At the other
extreme of the experimental spectrum, one finds strong liquids
that experience a gentle increase of the relaxation time, often
according to the Arrhenius law. Even in such systems, however,
when the viscosity becomes too large, equilibrium can no longer
be achieved on experimental timescales.

2) The glass transition temperature is conventionally defined as
that temperature at which the value of the viscosity is 10^(13)
poise. Below the glass transition temperature, equilibrium
experiments become difficult to perform and a sample can be
considered to be in its glass phase. However, the glass
transition temperature is merely a conventional experimental
temperature defined out of the need to mark the onset of glassy
dynamics. The attempt to give a theoretical description of such
an ill-defined “transition” may therefore seem pointless. On the
one hand, this conclusion is correct for the strongest liquids:
here nothing peculiar happens close to the glass transition
temperature , and the glass transition fully displays its purely
conventional nature. On the other hand, the most fragile systems
resist such an objection, simply by virtue of the extremely
steep increase of relaxation time within a small interval of
temperature around the glass transition temperature. This fact
suggests that some kind of new physical mechanism is indeed
responsible for the onset of the glassy phase in fragile
supercooled liquids.

3) The authors report they numerically studied the potential
energy landscape of a fragile glassy system and found that the
dynamic crossover corresponding to the glass transition is
actually the effect of an underlying geometric transition caused
by the vanishing of the instability index of saddle points of
the potential energy. Furthermore, the authors demonstrate that
the potential energy barriers connecting local glassy minima
increase with decreasing energy of the minima, and they relate
this behavior to the fragility of the system. Finally, the
authors analyze the real space structure of activated processes
by studying the distribution of particle displacements for local
minima connected by simple saddles.

References (abridged):

1. C. A. Angell, J. Phys. Chem. Solids 49, 863 (1988).

2. M. Goldstein, J. Chem. Phys. 51, 3728 (1969).

3. F.H. Stillinger and T.A. Weber, Phys. Rev. A 25, 978 (1982).

4. A. Cavagna, Europhys. Lett. 53, 490 (2001).

5. J. Kurchan and L. Laloux, J. Phys. A 29, 1929 (1996).

Phys. Rev. Lett. 2002 88:055502

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8. A LABORATORY ANALOGUE OF THE BLACK HOLE EVENT HORIZON

Ulf Leonhardt (University of St. Andrews, UK) discusses event
horizons, the author making the following points:

1) Optical media govern the propagation of light. Such media are
usually transparent substances such as glass or water, but empty
yet curved space is a medium as well. Certain material media can
be manipulated to give them extraordinary optical properties.
Inside such media light may propagate with a negative or very
low group velocity, or may be brought to a standstill. In a
medium with electromagnetically induced transparency, an
external control beam dictates the group velocity of a second
and weaker probe beam in order to slow down the probe light.
Once the first beam has gained control, the group velocity of
the second beam is essentially proportional to the control
intensity, even in the limit when the control intensity vanishes.

Singularities underlie many optical phenomena. The rainbow, for
example, involves a particular type of singularity — a "ray
catastrophe" — in which light rays become infinitely intense. In
practice, the wave nature of light resolves these infinities,
producing interference patterns. At the event horizon of a black
hole, time stands still and waves oscillate with infinitely
small wavelengths. However, the quantum nature of light results
in evasion of the catastrophe and the emission of Hawking
radiation.

The author reports a theoretical laboratory analogue of an event
horizon: a parabolic profile of the group velocity of light
brought to a standstill in an atomic medium can cause a wave
singularity similar to that associated with black holes. In
turn, the quantum vacuum is forced to create photon pairs with a
characteristic spectrum, a phenomenon related to Hawking
radiation. The author suggests the idea may initiate a theory of
"quantum catastrophes", extending classical catastrophe theory.

References (abridged):

1. Berry, M. V. & Upstill, C. Catastrophe optics: morphologies
of caustics and their diffraction patterns. Prog. Opt. XVII,
257-346 (1980).

2. Misner, Ch. W., Thorne, K. S. & Wheeler, J. A. Gravitation
(Freeman, New York, 1999).

3. Hawking, S. M. Black hole explosions? Nature 248, 30-31
(1974).

4. Liu, Ch., Dutton, Z., Behroozi, C. H. & Hau, L. V.
Observation of coherent optical information storage in an atomic
medium using halted light pulses. Nature 409, 490-493 (2001).

5. Philips, D. F., Fleischhauer, A., Mair, A., Walsworth, R. L.
& Lukin, M. D. Storage of light in atomic vapor. Phys. Rev.
Lett. 86, 783-786 (2001).

Nature 2002 415:406

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9. ON THE PREDICTABILITY OF EARTHQUAKES

The dominant cooling mechanism on Earth is "plate tectonics",
which involves the movement of 8 large plates and a few dozen
smaller plates, the motion driven from beneath by convection
within the mantle. On Earth, plate tectonics concentrates most
of the volcanoes, earthquakes, and other tectonic features along
plate margins rather than scattering them evenly throughout the
crust. The San Andreas fault in California, for example, is a
strike-slip fault at the interface between the Pacific plate (an
oceanic plate) and the North American plate (a continental
plate). 

Geophysical faulting is a break in rock structure that occurs
when pressures in the planet's crust are strong enough to cause
fracture and displacement. A strike-slip fault is a movement
parallel to the fault plane, the two plates shifting
tangentially in opposite directions along their interface. The 2
other major types of faults are 1) the "normal" fault, which
consists of a simple vertical shifting at the interface, one
plate moving up and the other down, and 2) the thrust fault,
which involves the edge of one plate sliding over (overlapping)
the edge of the adjacent plate.

The term "dilatancy" refers in general to an increase in the
volume of a rock deformed by pressure, the increase in volume
caused by the expansion and extension of small cracks within the
rock. The effect can be detected in strained rocks just before
an earthquake, and is the basis of one type of earthquake
prediction.

C.G. Sammis and D. Sornette (University of Southern California,
US) discuss the predictability of earthquakes, the authors
making the following points:

1) Are earthquakes predictable? The answer, of course, depends
on what is meant by a "prediction". In the broadest sense, the
plate tectonics paradigm makes predictions. It predicts that
earthquakes are far more likely to occur at the boundaries
between plates than within their interiors. Actually, plate
tectonics theory was in part based on this "in-sample"
observation, which is verified continuously "out-of-sample." It
also predicts an overall rate to the process. Averaged over
time, the summed moments of the earthquakes is consistent with
the relative motion between the plates determined from the
analysis of magnetic anomalies, correcting for aseismic
visco-plastic deformations.

2) The forecasting of individual large events has been more
problematical. Although the paleoseismological dating of large
prehistoric earthquakes has confirmed the plate tectonics
hypothesis, the timing between individual events is extremely
erratic. For example, the average recurrence interval for the
last ten large earthquakes on the San Andreas Fault north of Los
Angeles is approximately 132 years. Because the long-term slip
rate on the Southern San Andreas fault is approximately 3
centimeters per year, this corresponds to an average
displacement of approximately 4 meters per large earthquake -- a
very reasonable value. The problem is that the intervals between
events range from 44 to 332 years. This lack of quasiperiodicity
in large events is also evident in other predictions, and
observations have dimmed the hope that large earthquakes can be
forecast based solely on the past history of large events on the
same fault.

3) An alternative forecasting strategy is based on physical
precursors observed to occur just before macroscopic failure in
the laboratory. Most of these precursors are associated with
microfracture damage and the associated dilatancy observed to
precede the formation of a macroscopic shear failure of rock
specimens under compressive loading. These laboratory
observations have been incorporated into the
"dilatancy-diffusion model" for earthquakes. However, the search
for physical precursors before large earthquakes has been
disappointing. The high hopes raised by the reports of Chinese
success in using physical precursors to forecast the 1975
Haicheng earthquake have dissipated with the worldwide failure
to produce additional valid predictions.

4) In the US, current work on earthquake prediction is primarily
based on the search for precursors to large events in the
seismicity itself. One motivation comes from a statistical
physics interpretation of regional seismicity as being
characteristic of a system at or near a statistically stationary
dynamical critical point dubbed "self-organized criticality".
Such a self-organized critical state is characterized by power
law distributions of event sizes and long-range spatial
correlation of fluctuations around the statistically stationary
state. Because earthquakes are indeed characterized by several
power laws, the application of this concept of self-organized
criticality to earthquakes is now often taken for granted in the
seismological community. However, the implication of this
self-organized critical (statistically stationary) state for the
predictability of large earthquakes remains controversial.

References (abridged):

1. Sieh, K. , Stuiver, M. & Brillinger, D. (1989) J. Geophys.
Res. B 94, 603-623.

2. Bakun, W. H. & McEvilly, T. V. (1984) J. Geophys. Res. B 89,
3051-3058.

3. Nur, A. (1972) Bull. Seismol. Soc. Am. 62, 1217-22.

4. Whitcomb, J. H. , et al (1973) Science 180, 632-641.

5. Scholz, C. H. , Sykes, L. R. & Aggarwal, Y. P. (1973) Science
181, 803-809.

Proc. Nat. Acad. Sci. 2002 99:2501

PHYSICS OF EARTHQUAKES

H. Kanamori and E.E. Brodsky (California Institute of
Technology) discuss current research in the physics of
earthquakes. The recent earthquakes in Taiwan, Turkey, and India
tragically demonstrated the abruptness with which earthquakes
occur and the devastation that often accompanies them. In
general, earthquakes are sudden fractures in the Earth's crust
followed by ground shaking, and there are many questions
concerning these phenomena. When do earthquakes occur? What
long-term processes and short- term triggers produce
earthquakes? Although *plate tectonics has provided a successful
framework for understanding the long-term processes, the
short-term triggers remain obscure, making earthquakes
unpredictable. An equally important question and a fundamental
challenge to the science of geophysics is, What happens during
an earthquake? What are the forces and motions during a seismic
event? The answer to this question has practical consequences
for mitigating the effects of the expected ground motion. Most
earthquakes occur at depths down to 50 kilometers, but some
earthquakes as deep as 670 kilometers have been observed in
certain regions. Seismologists have never directly observed
ruptures in Earth's interior. Instead, they rely on the
information gleaned from the few available types of data, the
most important of which is the record of seismic waves. During
an earthquake, sudden crustal motion excites elastic waves that
travel through Earth and are observable at seismic stations on
the surface, and these waves carry information about movements
at the source of the earthquake.

Physics Today 2001 June

... ... *plate tectonics: The term "lithosphere" refers to the
outer layer of the Earth, comprising the crust and upper mantle,
and extending to a depth of 50 to 70 kilometers. The traditional
view of tectonics (changes in the structure of the Earth's
crust) is that the lithosphere consists of a strong brittle
layer overlying a weak ductile layer. "Plate tectonics" is the
current consensus theory that the Earth's lithosphere is broken
into fairly rigid plates, seven or eight major plates and many
smaller plates, and that convection within the underlying less
rigid "asthenosphere" causes the plates (and the associated
continents and crust) to move relative to each other.

Related Background:

EARTHQUAKES AND FRICTION LAWS

... The traditional view of tectonics is that the lithosphere
consists of a strong brittle layer overlying a weak ductile
layer, the system producing two forms of deformation, namely,
brittle fracture in the upper layer (accompanied by
earthquakes), and aseismic (without earthquakes) ductile flow in
the lower layer. The current consensus is that this view is
generally correct but imprecise, since the accumulated evidence
is now interpreted to indicate that frictional events along
fault lines, rather than new fractures, are the causes of
earthquakes. The essential idea is that fault lines, which are
the interfaces between the crustal plates, build up stresses
resulting from the movements of the plates, and at intervals
these stresses are suddenly relieved by interface slippages the
surface manifest- ations of which are earthquakes. In mechanics,
"stick-slip" friction is friction between two surfaces that are
alternately at rest and in motion with respect to each other,
and in recent years a number of laboratories have conducted
model experiments with stick-slip rock systems with the idea of
obtaining a fuller understanding of the physics of frictional
phenomena occurring at fault lines. C.H. Scholz (Columbia Univ.,
US), in a review of current ideas concerning earthquake
mechanics, points out that at present the most precise and
predictive model for earthquake mechanisms is that an earthquake
is a frictional rather than a fractional phenomenon, with
brittle fracture of the upper litho- sphere layer playing a
secondary role in the lengthening of faults and frictional wear.
The origin of earthquakes is evid- ently a stick-slip frictional
instability, and many of the aspects of earthquake phenomena can
apparently be explained by the general laws applying to
frictional stability regimes.

Nature 1998 1 Jan

Related Background:

THE PREDICTION OF EARTHQUAKES

Earthquake prediction, an aspect of geophysics of obvious
tremendous social and economic importance, demands from
geophysicists more than they are presently able to give.
Seismicity patterns, in conjunction with knowledge of where
historic earthquakes have occurred, permit reasonable judgments
of where future earthquakes are most likely to occur, but at
present it is not possible to predict when an earthquake is
likely to happen in an endangered area. And of course it is the
when that is of great social and economic and even political
importance. A recent published exchange of letters among
seismologists focuses on the problems of earthquake prediction,
the exchange provoked by a previous article which emphasized
that such predictions are not possible (R. J. Geller et al,
Science 275:1616 1997). Max Wyss (University of Alaska, US)
suggests that research in the physics of preparation for
catastrophic rupture should not be halted, and that if the lack
of funding for earthquake prediction research continues in the
US, the important discoveries will be made in Japan, Europe, or
China. Richard A. Aceves and Stephen K. Park (University of
California Riverside, US) suggest that the review by Geller et
al is "an unduly negative view of research in a difficult
field." But these authors admit it is time for present
earthquake prediction research to be more honestly identified as
earthquake monitoring. They suggest, however, that considering
the large benefit if and when such research will bear fruit,
earthquake prediction research should definitely continue.
Robert J. Geller et al (4 authors at 3 installations in JP, US,
IT), the authors of the review that provoked the letters,
respond that they believe emphasis should be placed on basic
research in earthquake science, real-time seismic warning
systems, and long-term probabilistic earthquake hazard studies.

Science 1997 17 Oct

Related Background:

DEFORMATIONS IN THE SAN ANDREAS FAULT LOWER CRUST A geophysical
fault is a break in rock structure that occurs when pressures in
the Earth's crust are strong enough to cause fracture and
displacement, and earthquakes are common at such break points.
Seismic velocity refers to the propagation velocity of a seismic
disturbance (e.g., an earthquake), and reflectivity
cross-section is a parameter associated with the reflective
properties of a propagated seismic wave. The Mohorovicic
Discontinuity (called "Moho" and named after Andrija
Mohorovicic, who first identified it in 1909) represents the
boundary between the crust and mantle, its depth varying from
about 5 kilometers to as much as 60 to 80 kilometers. A
strike-slip fault is a movement parallel to the fault plane, and
the San Andreas fault of California is of this type. Continental
drift is the slow movement of the Earth's land masses, a
shifting across the underlying molten material, and sea-floor
spreading is the process whereby sea floor is continuously
created as the crustal plates move apart and continuously
destroyed where the plates push against each other. And finally,
plate tectonics is the modern theory that unifies many of the
features and character- istics of continental drift and
sea-floor spreading into a coherent model. Timothy J. Henstock
et al (3 authors at 2 installations, US) now report that
analysis of a continuous seismic velocity and reflectivity
cross-section of the San Andreas fault system in northern
California reveals offsets in the lower crust and the
Mohorovicic Discontinuity near the San Andreas and Maacama
strike-slip faults, and that the northern California continental
margin to the eastern edge of the Coastal Ranges is underlain by
a high-velocity lowermost crustal layer that may have been
emplaced within 2 million years following the removal of the
plate slab known as the Gorda plate. The authors suggest that
the rapid emplacement and structure within this layer are
difficult to reconcile with existing tectonic models.

Science 1997 24 Oct

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10. ASTROPHYSICS: ON LOCAL AND DISTANT GALAXIES

Francesco Bertola (University of Padova, IT) discusses galaxies,
the author making the following points:

1) In our expanding universe, radiation emitted by astronomical
objects appears more redshifted the farther the objects are from
us. Galaxies close to our own galaxy have low redshift and are
relatively old; galaxies at high redshift are distant and hence
young. The advent of the Hubble Space Telescope and of large (8
to 10 meters) ground-based telescopes during the last decade has
greatly facilitated the study of distant young galaxies.
Comparison of the local universe with the early universe is
providing insights into how galaxies have evolved on a
cosmological time scale.

2) The latest value for the mass of our galaxy's dark halo
(which holds most of the galaxy's mass) is about 2 x 10^(12)
solar masses. Just 15 years ago, the best estimate for the total
mass of our galaxy was an order of magnitude lower. The current
value has been derived from state-of-the-art data for the radial
velocities of the globular clusters (gravitationally bound
concentrations of 10,000 to 1 million stars) that surround our
galaxy and of nearby "satellite" galaxies. These objects serve
as tracers for our galaxy's gravitational potential and hence
its mass. A much higher accuracy will be achieved when the
radial and transverse velocities of the satellite galaxies have
been determined by GAIA, a space mission to be launched in 2010.

3) A lively current debate in the astronomy community concerns
the processes leading to the formation of galaxies. The key
question is whether all galaxies formed early on through
gravitational collapse in a "monolithic collapse" event and have
since evolved in isolation, or whether they are the result of
successive mergers between ever larger structures ("hierarchical
merging"). These models lead to different distributions of dark
mass in galaxies. Numerical simulations suggest that in the
hierarchical merging scenario, dark matter should peak in the
centers of galaxies. Systematic study of the rotation curve of
low-surface-brightness galaxies, which are believed to be
dominated by dark matter, reveals that the density distribution
is better fitted by a model with a central constant density core
than with a peaked distribution, suggesting that more efforts
are needed to reconcile simulation and observation.

References (abridged):

1. The Mass of Galaxies at Low and High Redshift, workshop
organized by ESO and the Universitäts-Sternwarte München,
Venice, 24 to 26 October 2001; see
http://www.eso.org/gen-fax/meetings/gmass2001

2. M. I. Wilkinson, N. W. Evans, Mon. Not. R. Astron. Soc. 310,
645 (1999). GAIA stands for Global Astrometric Interferometer
for Astrophysics

3. R. P. Olling, M. Merrifield, Mon. Not. R. Astron. Soc. 311,
361 (2000)

4. R. P. Olling, Mon. Not. R. Astron. Soc. 326, 164 (2001)

5. S. S. McGaugh, V. C. Rubin, W. J. G. de Blok, Astron. J. 122,
2381 (2001)

Science 2002 295:283

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11. ON BINARY WATER-SURFACTANT SYSTEMS

M. Nekovee and P.V. Coveney (University of London, UK) discuss
binary water-surfactant systems, the authors making the
following points:

1) Periodic arrangements of two fluid media separated by
interfaces are very common in liquid crystals where they most
often occur as a periodic stacking of layers of fluids in one
dimension. In lamellar phases of lyotropic liquid crystals,
built by amphiphilic molecules in the presence of water,
bilayers of amphiphiles and layers of water are alternatively
stacked with flat interfaces defined by the polar heads of the
amphiphiles. Besides these phases, which exhibit periodicity
along one direction, the phase diagrams of amphiphilic systems
may present other ordered phases with periodicity along two or
three dimensions, curved interfaces, and various other more
exotic topologies. One of the intriguing aspects of amphiphilic
polymorphism is the existence of phases with long-range cubic
order and bicontinuous geometry that can be traversed in any
direction in both the water-rich and the surfactant-rich
regions. These phases have been observed experimentally in
amphiphilic-water phase diagrams close to the lamellar phase
domain where the concentration of the surfactant is high.

2) The equilibrium properties and stability of these structures
have been studied in the past using macroscopic curvature models
that give the energy cost of bending a membrane-like interface.
However, the dynamics of self-assembly of such ordered
structures, together with the dynamics of phase transitions, are
beyond the scope of such equilibrium approaches. On the other
hand, the time and length scales involved in the self-assembly
of such mesophases makes fully microscopic descriptions (based
on molecular dynamics) computationally prohibitive.

3) The authors report they have used their recently developed
"lattice-Boltzmann" method to study, on a mesoscopic level, the
dynamics of self-assembly of the bicontinuous cubic phase in a
binary water-surfactant system, and the transition from the
lamellar structure, with flat interfaces, to a bicontinuous
cubic phase, with minimum curvature. The authors suggest their
study provides insight into how such structures emerge as a
result of competing molecular interactions between water and
amphiphiles and among amphiphilic molecules themselves. The
authors point out that this study also represents the first
application of any lattice-Boltzmann model to the study of
amphiphilic systems in three-dimensions.

References (abridged):

1. Gompper, G.; Schick, M. Phase Trans. Crit. Phenom. 1994, 16,
1.

2. Micelles, Membranes, Microemulsions and Monolayers', Gelbart,
W. M., Ben-Shaul, A., Roux, D., Eds.; Springer: New York, 1994.

3. See e.g., Lindblom, G.; Rillfors, L. Biochim. Biophys. Acta
1989, 988, 222-249; Seddon J. M, Biochim. Biophys. Acta 1990,
1031, 1-69.

4. Schwartz, U. S.; Gompper, G. Phys. Rev. Lett. 2000, 85,
1472-1475.

5. Gompper, G.; Klein, S. J. Phys. II (France) 1992, 2,
1725-1744.

J. Am. Chem. Soc. 2001 123:12380

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12. GLOBAL ASYMMETRY OF THE PLANET MARS

Peter Gierasch (Cornell University, US) discusses the planet
Mars, the author making the following points:

1) Mars is an asymmetrical planet. Its northern hemisphere is
relatively smooth and free of craters, with a large, permanent
ice-cap that is mainly composed of water. The southern polar cap
is smaller and contains carbon dioxide, and the surrounding
terrain is heavily cratered. Hemispheric dichotomies are not
unusual in the Solar System. The Moon, for example, has
extensive lava plains on the side facing the Earth and is
heavily cratered on the other side. Unlike the Moon, however,
Mars has an atmosphere that can transport dust and water vapor
around the planet. So one might expect that over the long term
mixing would lead to a balanced distribution of polar ice. But
this is not what is observed.

2) Mars has an elliptical orbit around the Sun, with an
eccentricity of 0.093 (an eccentricity of 0.0 would be a
perfectly circular orbit). The axis of rotation is tilted away
from the normal by 25.1 degrees. Thus Mars has seasons similar
to the Earth's, but the seasons are exaggerated and more
asymmetrical. At present, summer in the Martian southern
hemisphere occurs near perihelion — that part of its orbit when
the planet is closest to the Sun. At this point, Mars is
approximately 20 percent closer to the Sun than it is during the
northern hemisphere summer. Thus, one possible cause of the
observed asymmetry is that southern hemisphere summers are much
warmer than northern hemisphere summers. Another possibility
lies in the fact that the terrain in the southern hemisphere is
on average higher than that in the north. But study of these
factors has produced no widely accepted explanation for the
asymmetries in water distribution, and the observations thus
remain puzzling.

3) Richardson and Wilson (2002) have recently proposed that
atmospheric transport of water and dust, rather than tending to
redistribute material uniformly, in fact acts as a pump across
the Martian equator and contributes to the north–south asymmetry
in ice coverage. It may also produce an imbalance in the
distribution of surface dust deposits, although the absence of
depth measurements of the deposits means that this possibility
remains speculative. Mars has no ocean, and therefore the
atmosphere is the only medium for transportation on the planet.
In summary, some of the differences between the northern and
southern hemispheres of Mars may stem from asymmetry in the
planet's atmospheric circulation, and the resulting asymmetric
distribution of water and dust.

References (abridged):

1. Richardson, M. I. & Wilson, R. J. Nature 416, 298-301 (2002).

2. Kieffer, H. H. & Zent, A. P. in Mars (eds Kieffer, H. H.,
Jakosky, B. M., Snyder, C. W. & Matthews, M. S.) 1180-1218
(Univ. Arizona Press, Tucson, 1992).

3. Jakosky, B. M. & Haberle, R. M. in Mars (eds Kieffer, H. H.,
Jakosky, B. M., Snyder, C. W. & Matthews, M. S.) 969-1016 (Univ.
Arizona Press, Tucson, 1992).

4. James, P. B., et al,  in Mars (eds Kieffer, H. H., Jakosky,
B. M., Snyder, C. W. & Matthews, M. S.) 934-968 (Univ. Arizona
Press, Tucson, 1992).

5. Lindzen, R. S. & Hou, A. Y. J. Atmos. Sci. 45, 2416-2427
(1988).

Nature 2002 416:269

Also:

Ex Link: The Planet Mars: A History of Observation and Discovery

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13. ON SCHISTOSOMIASIS

A.G. Ross et al (Medical University of the Americas, KN) discuss
schistosomiasis, the authors making the following points:

1) In 1851, Theodor Bilharz (1829-1862) described a parasitic
infection (bilharzia) that would later be termed
schistosomiasis. Currently, 200 million people in 74 countries
have this disease; 120 million of them have symptoms, and 20
million have severe illness. Schistosomiasis is caused by
parasitic trematode worms (schistosomes) that reside in the
abdominal veins of their vertebrate definitive hosts.

2) Five species of schistosoma are known to infect humans.
Infection with Schistosoma mansoni, S. japonicum, S. mekongi, or
S. intercalatum is associated with chronic hepatic and
intestinal fibrosis. S. haematobium infection results in
fibrosis, stricturing, and calcification of the urinary tract.
All schistosoma infections follow direct contact with fresh
water that harbors free-swimming larval forms of the parasite
known as cercariae. Cercariae penetrate the skin of humans or,
in the case of S. japonicum, humans and other mammalian hosts
that act as reservoirs for infection. The cercariae shed their
bifurcated tails, and the resulting schistosomula enter
capillaries and lymphatic vessels en route to the lungs. After
several days, the worms migrate to the portal venous system,
where they mature and unite. Pairs of worms then migrate to the
superior mesenteric veins (in the case of S. mansoni ), the
inferior mesenteric and superior hemorrhoidal veins (in the case
of S. japonicum), or the vesical plexus and veins draining the
ureters (in the case of S. haematobium). Egg production
commences four to six weeks after infection and continues for
the life of the worm — usually three to five years. Eggs pass
from the lumen of blood vessels into adjacent tissues, and many
then pass through the intestinal or bladder mucosa and are shed
in the feces (in the case of S. mansoni and S. japonicum) or
urine (in the case of S. haematobium). The life cycle is
completed when the eggs hatch, releasing miracidia that, in
turn, infect specific freshwater snails (S. mansoni infects
biomphalaria species, S. haematobium infects bulinus species,
and S. japonicum infects oncomelania species). After two
generations — primary and then daughter sporocysts — within the
snail, cercariae are released.

3) Despite major advances in control and substantial decreases
in morbidity and mortality, schistosomiasis continues to spread
to new geographic areas. Furthermore, there are reports of
resistance to praziquantel, the mainstay of medical treatment.
The majority of Schistosoma haematobium, S. mansoni, and S.
intercalatum infections are found in sub-Saharan Africa. S.
mansoni remains endemic in parts of Brazil, Venezuela, and the
Caribbean. S. japonicum infection still occurs in China,
Indonesia, and the Philippines, despite substantial and largely
successful control measures. S. mekongi is found in Cambodia and
Laos, along the Mekong River.

4) Environmental changes that result from the development of
water resources and the growth and migration of populations can
facilitate the spread of schistosomiasis. For example, the
construction of Diama Dam on the Senegal River led to the
introduction of S. mansoni into Mauritania and Senegal. The
movement of refugees and the displacement of populations
resulted in the introduction of S. mansoni into Somalia and
Djibouti. The presence of the Aswan Dam in Egypt has led to the
virtual elimination of S. haematobium from the Nile Delta but
has brought about the establishment of S. mansoni in upper
Egypt. The Three Gorges Dam is currently being built on China's
Yangtze River between two areas where schistosomiasis is
endemic. The Chinese Ministry of Health is currently evaluating
the potential effect of the dam on schistosomiasis transmission.

References (abridged):

1. Chitsulo L, Engels D, Montresor A, Savioli L. The global
status of schistosomiasis and its control. Acta Trop
2000;77:41-51

2. Jordan P, Webbe G, Sturrock R. Human schistosomiasis.
Wallingford, England: CAB, 1993.

3. Waine GJ, McManus DP. Schistosomiasis vaccine development --
the current picture. Bioessays 1997;19:435-443

4. Morel C. Reaching maturity -- 25 years of the TDR. Parasitol
Today 2000;16:522-528

5. Newman L. Worm infections fester as experts vie for fair
share of funding. Lancet Infect Dis 2001;1:140.

New Engl. J. Med. 2002 346:1212

Also:

Ex Link: Schistosomiasis: A Review

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14. ANALYSIS OF DNA MICROARRAYS BY RULE-BASED COMPUTATION

K-H. Pan et al (Stanford University, US) discuss DNA
microarrays, the authors making the following points:

1) Although DNA microarrays now enable the expression of
thousands of genes to be assessed simultaneously at the
transcription level, the interpretation of microarray data
remains a significant challenge. Analysis of microarrays has
used both unsupervised methods that group genes showing
quantitative similarities in expression, and approaches that
exploit machine knowledge in a supervised manner during the
course of gene grouping. While unsupervised methods such as
hierarchical clustering, K-means clustering, and the generation
of self-organizing maps are entirely statistical, the assignment
of biological relevance to the resulting gene groupings involves
the post hoc application of knowledge, and interpretation may
vary widely according to the expertise and experience of
individual users. Often, the parameters used to produce sensible
classifications are not explicitly defined or transparent to
others.

2) Expert knowledge can be incorporated into computer systems to
accomplish defined tasks and can be formulated as rules that
consist of premises and conclusions. One of the earliest
rule-based systems to focus successfully on a biomedical problem
was MYCIN, which used modules of knowledge acquired from
infectious disease experts to analyze clinical and laboratory
data and make recommendations to physician practitioners for the
diagnosis and treatment of infections. The premises of each
MYCIN rule contained conditions that, if satisfied, allowed a
specified conclusion to be made. MYCIN also could explain in
English how a conclusion was reached by reciting the premises on
which it was based and could gain new knowledge by a
rule-acquisition function. MYCIN rules were discrete and largely
independent, allowing the program to flexibly increase its base
of knowledge. The MYCIN inference engine EMYCIN and its
successors have since been used for a variety of diagnostic
purposes.

3) The authors describe GABRIEL (Genetic Analysis By Rules
Incorporating Expert Logic), a rule-based computer system
designed to apply domain-specific and procedural knowledge
systematically for the analysis and interpretation of data from
DNA microarrays. GABRIEL, which has some of the key features of
MYCIN, stores knowledge in the form of preformatted rules or as
rules acquired from users through a graphical interface; it then
applies this knowledge during the process of gene
classification. A rule-explanation capability makes explicit and
transparent to users the criteria and reasoning used by GABRIEL
to generate groupings. The knowledge contained in GABRIEL rules
also allows inferences to be made about the significance of
changes in gene expression, the mechanisms underlying these
changes, and genetic regulatory relationships. This initial
description of GABRIEL compares the program's output with
published conclusions reached by investigators that have
interpreted microarray results generated by hierarchical
clustering.

References (abridged):

1. Quackenbush, J. (2001) Nat. Rev. Genet. 2, 418-427

2. Sherlock, G. (2000) Curr. Opin. Immunol. 12, 201-205

3. Brazma, A. & Vilo, J. (2000) FEBS Lett. 480, 7-24

4. Brown, M. P. , et al. (2000) Proc. Nat. Acad. Sci. 97, 262-267

5. Furey, et al. (2000) Bioinformatics 16, 906-914

Proc. Nat. Acad. Sci. 2002 99:2118

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15. PATTERNS OF ADULT MEDICATION USE IN THE US

1) D.W. Kaufman et al (Boston University, US) discuss patterns
of medication use, the authors making the following points:

1) A large number and wide variety of medications approved for
use by the US Food and Drug Administration (FDA) are available
to the US population, and expenditures on drugs have increased
dramatically in recent years. New prescription drugs are
continually introduced, and older drugs are increasingly
available over the counter, making self-medication commonplace.
Adverse reactions to drugs are among the leading causes of
hospitalization and death in the US. At the same time, there has
been a considerable increase in the use of herbal products and
other natural supplements (henceforth referred to as
"herbals/supplements"), which by law are not subject to FDA
regulation. Although these products may be taken concurrently
with regulated medications, health care professionals are often
not informed of such use by their patients. Evidence is growing
that many herbals/supplements have pharmacologic activity that
can lead to clinically serious adverse interactions when they
are taken together with regulated drugs, but there is little
information available to estimate the potential magnitude of
this problem.

2) The authors report a telephone survey of a random sample of
the non-institutionalized US population in the 48 continental
states and the District of Columbia. Data analyzed were
collected from February 1998 through December 1999. The authors
report that among 2590 participants aged at least 18 years, 81
percent used at least 1 medication in the preceding week; 50
percent took at least 1 prescription drug; and 7 percent took 5
or more. The highest overall prevalence of medication use was
among women aged at least 65 years, of whom 12 percent took at
least 10 medications and 23 percent took at least 5 prescription
drugs. Herbals/supplements were taken by 14 percent of the
population. Among prescription drug users, 16 percent also took
an herbal/supplement. The rate of concurrent use was highest for
fluoxetine users, at 22 percent. Reasons for drug use varied
widely, with hypertension and headache mentioned most often (9
percent for each). Vitamins/minerals were frequently used for
nonspecific reasons such as "health" (35 percent);
herbals/supplements were also most commonly used for "health"
(16 percent).

3) The authors conclude: In any given week, most US adults take
at least 1 medication, and many take multiple agents. The
substantial overlap between use of prescription medications and
herbals/supplements raises concern about unintended interactions.

References (abridged):

1. Copeland C. Prescription drugs: issues of cost, coverage, and
quality. EBRI Issue Brief. 1999;208:1-21.

2. Baugh DK, Pine PL, Blackwell S. Trends in Medicaid
prescription drug utilization and payments, 1990-97. Health Care
Financ Rev. 1999; 20:79-105.

3. Mehl B, Santell JP. Projecting future drug expenditures2000.
Am J Health Syst Pharm. 2000;57:129-138.

4. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug
reactions in hospitalized patients: a meta-analysis of
prospective studies. JAMA. 1998; 279:1200-1205.

5. Bates DW. Drugs and adverse drug reactions: how worried
should we be?  JAMA. 1998;279:1216-1217.

J. Am. Med. Assoc. 2002 287:337

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16. ON TUMOR OXIMETRY

M.C. Krishna et al (National Institutes of Health, US discuss
tumor oximetry, the authors making the following points:

1) Abnormal values of pO(sub2) [the partial pressure of O(sub2)]
are linked to many pathophysiological conditions (e.g., ischemic
diseases, reperfusion injury, and oxygen toxicity).
Approximately one-third of human tumors evaluated for oxygen
status have shown significant oxygen deficiency, and oxygen
deficiency increases the tumor's resistance toward cancer
treatment modalities, including radiation and chemotherapy.
Additionally, hypoxic microenvironments in tumors are known to
promote processes driving malignant progression, such as
angiogenesis, elimination of p53 tumor suppressor activity,
genetic instability, and metastasis.

2) Understanding of tumor hypoxia could lead to the discovery of
diagnostic and prognostic markers for malignant progression,
discovery of novel therapeutic targets, and the development of
new constructs for gene therapy applications in human cancer.
Hence, a noninvasive technique that could accurately and
repetitively measure tissue oxygenation would find broad
application in clinical and basic research. Unfortunately, the
currently used electrochemical method for in vivo oxygen
measurement is an invasive technique applicable only to
accessible tumors. Further, the technique is hampered by
measurements of only a small part of the total tumor, which
cannot be re-evaluated. Several magnetic resonance techniques
have been developed for in vivo oximetry, including spin label
oximetry, magnetic resonance imaging (MRI), and electron
paramagnetic resonance imaging (EPRI). The blood oxygen
level-dependent effect, mainly used for functional MRI, has more
recently found application in evaluating efficacy of oxygenation
by certain oxygenating modalities in hypoxic tumors, but it does
not provide quantitative oximetry. Direct NMR measurements of
the proximal histidine of myoglobin or hemoglobin show much less
sensitivity than the water-proton-based experiments. F-19 MRI of
blood substitutes is also used for oximetry, but suffers from
chemical shift artifacts and low F-19 concentration in tissues.

3) The authors describe an efficient noninvasive method for in
vivo imaging of tumor oxygenation by using a low-field magnetic
resonance scanner and a paramagnetic contrast agent. The
methodology is based on Overhauser enhanced magnetic resonance
imaging (OMRI), a functional imaging technique. OMRI experiments
were performed on tumor-bearing mice (squamous cell carcinoma).
The authors suggest their work demonstrates that anatomically
coregistered pO2 maps of tumors can be readily obtained by
combining the good anatomical resolution of water-proton-based
MRI, and the superior pO2 sensitivity of EPR. OMRI affords the
opportunity to perform noninvasive and repeated pO2 measurements
of the same animal with useful spatial (1 millimeter) and
temporal (2 minutes) resolution, making this method a powerful
imaging modality for small animal research to understand tumor
physiology, and a method with potential human applications.

References (abridged):

1. Horsman, M. R. , Nordsmark, M. & Overgaard, J. (1998)
Strahlenther. Onkol. 174, 2-5

2. Stratford, I. J. , Adams, G. E. , Bremner, J. C. , Cole, S. ,
Edwards, H. S. , Robertson, N. & Wood, P. J. (1994) Int. J.
Radiat. Biol. 65, 85-94

3. Maxwell, P. H. , Dachs, G. U. , Gleadle, J. M. , Nicholls, L.
G. , Harris, A. L. , Stratford, I. J. , Hankinson, O. , Pugh, C.
W. & Ratcliffe, P. J. (1997) Proc. Natl. Acad. Sci. USA 94,
8104-8109

4. Hockel, M. , Schlenger, K. , Aral, B. , Mitze, M. , Schaffer,
U. & Vaupel, P. (1996) Cancer Res. 56, 4509-4515

5. Giaccia, A. J. (1996) Semin. Radiat. Oncol. 6, 46-58

Proc. Nat. Acad. Sci. 2002 99:2216

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17. COOPERATIVITY IN DRUG-DNA RECOGNITION

S.A. Harris et al (University Park Nottingham, UK) discuss
drug-DNA interactions, the authors making the following points:

1) The regulation of transcription is frequently mediated
through specific interactions between complex regulatory
assemblies of proteins and an array of DNA sites that are often
separated by significant distances. A ubiquitous feature of
these regulatory complexes is that they are assembled highly
cooperatively in order to enhance binding affinity, sequence
selectivity, and sensitivity to protein concentration.
Homeodomain DNA binding proteins bind as a dimer to the
palindromic DNA sequence TAATCTGATTA, composed of two inverted
TAAT motifs. Protein-protein interactions are evident in the
complex; however, changes in DNA conformation (a 21 degree bend)
are also essential for the highly cooperative dimer-DNA
interaction. Studies of the interaction of a number of
homeodomain monomers show that they also produce significant
conformational changes in the DNA, presenting strong evidence
that cooperative binding is mediated by DNA conformational
changes brought about by an initial binding event that enhances
the affinity for the second site.

2) It is also becoming clear that cooperativity can operate in
sequence-selective drug-DNA recognition. The DNA
bis-intercalating anti-tumor antibiotic echinomycin binds
preferentially to CpG sites; NMR and footprinting analysis of
the interaction of the drug with the sequences ACGTACGT and
ACGTATACGT shows that drug molecules bind cooperatively to the
two CpG sites. In contrast, cooperative interactions are
disrupted by the sequence TCGATCGA, demonstrating that sequence
specific effects are responsible for mediating information
transfer between sites.

3) The authors report a series of molecular dynamics simulations
on the free DNA, the 1:1 complex, and the 2:1 complex, the
simulations designed to enable the calculation of thermodynamic
parameters associated with molecular recognition events. The
results of the molecular dynamics studies confirm that
structural factors alone cannot explain the cooperativity
observed. Indeed, when enthalpic and hydration factors are
looked at in isolation, the recognition process is predicted to
be slightly anti-cooperative. However, when changes in
configurational entropy are taken into account as well, the
overall free energy differences are such that the calculated
cooperativity is in good agreement with that observed
experimentally. The authors suggest their results demonstrate
the power of molecular dynamics methods to provide reasonable
explanations for phenomena that are difficult to explain on the
basis of static models alone, and provide an example of the
concept of "allostery without conformational change".

References (abridged):

1. Tjian, R.; Mitchell, P. J. Science 1989, 245, 371-378.

2. Sorger, P. K. B.; Pelham, H. R. Cell 1988, 54, 855-864.

3. Gehring, W. J.; Affolter, M.; Burglin, T. Annu. Rev. Biochem.
1994, 63, 487-526.

4. Laughon, A. Biochemistry 1991, JO, 11357-11367.

5. Duboule, D. Guidebook to the Homeodomain Genes; Oxford
University Press: Oxford, 1994.

J. Am. Chem. Soc. 2001 123:12658

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18. COMPLEXITY OF THE HUMAN GENOME AND BIOMEDICAL RESEARCH

Thomas D. Pollard (Yale University, US) discuss future
biomedical research, the author making the following points:

1) The author poses the question: How can the research community
handle the complexity presented by 35,000 human genes and
100,000 proteins? Evolution is responsible for this genetic
complexity, but the very nature of molecular evolution also
provides the salvation for dealing with the inherent complexity.
Ancient genomes were much simpler than ours, consisting of
hundreds to a few thousand genes. Genomes became more
complicated by events that copied and shuffled pieces of DNA.
Some events created a duplicate copy of an existing gene,
allowing the sequences of the 2 genes to diverge over time. In
other cases, cutting and pasting bits of the genome brought
together novel combinations of sequences that coded for proteins
with new functions.

2) For example, a long time ago a prokaryote developed a gene
encoding a protein with 7 alpha-helices spanning the plasma
membrane. Modern day Archaebacteria use such a protein to absorb
light and transduce its energy to transport protons out of the
cell. Over millions of years, mutations accumulated in such
genes that allowed 7-helix receptors in protozoa to bind
chemicals from the environment and to transmit signals into the
cytoplasm for chemotaxis toward food. Over time the original
gene for this 7-helix receptor was duplicated, and chance
mutations in the 2 copies allowed them to diverge until one gene
product was able to recognize a different environmental
chemical. If this conferred a selective advantage on the
organism, both genes were preserved. Multiple rounds of
duplication and divergence of sequences led to the human genome,
which contains approximately 1000 7-helix receptors.
Approximately 500 of these receptors are used to detect
particular odorant molecules. Others bind hormones,
neurotransmitters, growth factors, and many clinically useful
drugs. The beta-adrenergic receptors in the heart and liver are
only one example. Although each receptor is specialized to bind
to a particular type of chemical, all of these receptors send
their signal into the cell using the same strategy and similar
molecular machinery.

Since in-depth analysis is required to understand even the
simplest molecular machine, it is impossible (and a waste of
time) to characterize all 7-helix receptors or each of the
products of other multigene families such as protein kinases.
Knowing how a few examples work reveals general principles about
how the other members of the same family work as well.

The few physiological processes that are understood in detail
(protein synthesis, adenosine triphosphate synthesis, muscle
contraction, action potentials) have established that life
depends on an ensemble of complicated chemical reactions. One
strategy, the reductionist approach, has successfully linked
molecules to physiology time-after-time and is expected to
reveal the mechanisms of more complicated life processes. Taking
this approach, biological systems are reduced to their component
parts, which are characterized individually and then
reconstituted to reproduce the physiological process. Genetic or
pharmacological experiments allow molecular mechanisms to be
tested at the cellular and organismic levels. The combined
application of human genetics and the reductionist approach to
mechanisms will reveal the molecular basis of most human
diseases.

References (abridged):

1. McKusick VA. Online Mendelian Inheritance in Man (OMIM).
Available at: http://www.ncbi.nlm.nih.gov/omim  Accessibility
verified March 6, 2002.

2. Semsarian C, Seidman CE. Molecular medicine in the 21st
century. Intern Med J. 2001;31:53-59.

3. Lanyi J. Bacteriorhodopsin as a model for proton pumps.
Nature. 1995;375:461-463.

4. Green R, Noller HF. Ribosomes and translation. Annu Rev
Biochem 1997;66:679-716.

5. Pollard TD, Blanchoin L, Mullins RD. Biophysics of actin
filament dynamics in nonmuscle cells. Annu Rev Biophys Biomol
Struct. 2000;29:545-576.

J. Am. Med. Assoc. 2002 287:1725

Related Background:

ON THE CODING CAPACITY OF THE HUMAN GENOME

R.L. Strausberg and G.J. Riggins (National Cancer Institute, US)
discuss the human "transcriptome", the repertoire of actual
transcripts from the human genome. The potential coding capacity
of the human genome is currently a topic of great interest. The
number of genes predicted from the recent human-genome analysis
was at the lower end of previous estimates, which had ranged
from approximately 30,000 to 120,000. Whereas estimates of gene
number are likely to increase based on additional experimental
evidence and improved gene-finding algorithms, it is clear that
gene number is only one mechanism for creating the genetic
diversity required to encode the full complement of human
proteins. The scientific literature richly describes the
presence and functional significance of alternatively processed
forms of human transcripts that are derived from different
transcription initiation sites, alternative exon splicing, and
multiple polyadenylation sites. Determining the various
transcript forms and investigating the purpose of these complex
mixtures of instructions will be the next great endeavor toward
understanding human biology. Imperative to an elucidation of the
transcriptome will be the development of new technologies and
scientific strategies. We will need to identify and analyze not
only different transcripts from a single gene, but we will also
need to examine the entirety of the transcript population of
cells and tissues so that we can begin to understand the
networks of interactions encoded by various transcript forms.
Undoubtedly, innovation will be a hallmark of transcriptome
research for the next several years.

Proc. Nat. Acad. Sci.  2001 98:11837

Related Background:

GENETICS: THE FUTURE OF HUMAN GENOME RESEARCH

The recent sequencing (I. Dunham et al: Nature 402:489 1999) of
the major part of the human chromosome 22 represents the first
step of what will be one of the most important accomplishments
in the near future -- the complete sequencing of the entire
human genome. The chromosome 22 sequence obtained consists of 12
contiguous segments spanning 33.4 million nucleotide bases,
contains at least 545 genes and 134 "*pseudogenes", and is
believed to provide the first view of the complex chromosomal
landscapes that will be found in the rest of the human genome.

... ... Peter Little (Imperial College London, UK) presents a
commentary on human genome research and the sequencing of human
chromosome 22, the author making the following points:

1) The first protein to be sequenced was insulin (1951). The
first genome to be sequenced was that of the bacterium
Haemoophilus influenza (1995). The author provides the following
historical timetable of reasearch leading to the sequencing of
the human genome:

... ... 1866: Discovery of genes by Gregor Mendel (1822-1884).

... ... 1871: Nucleic acids discovered.

... ... 1951: First protein sequence.

... ... 1953: Structure of DNA

... ... 1960s: Elucidation of the genetic code.

... ... 1977: Advent of DNA sequencing.

... ... 1975-1979: First human genes isolated.

... ... 1986: DNA sequencing automated.

... ... 1995: First whole genome.

... ... 1999: First human chromosome sequenced.

... ... 2002: Completion of human genome sequence.

2) The author suggests that the sequencing of human chromosome
22 is the first chapter of the "book of genes". The whole of the
book will probably never be printed in its entirety -- it would
require approximately half a million printed journal pages --
but it will nevertheless unquestionably alter our perceptions of
human health, attitudes toward each other, and our understanding
of our uniqueness. "It is fitting that in this age our most
telling monument, a culmination of some of the great biological
discoveries of our time may be an electronic database."

3) The DNA in all normal human cells is in 23 pairs of pieces,
neatly packaged into 46 chromosomes. Chromosome 22 was chosen to
be sequenced first because it is one of the smallest human
chromosomes (only chromosome 21 is smaller). The published
sequence is not quite complete: for technical reasons, the
sequence contains 11 gaps, ranging from a few thousand to
150,000 base pairs.

4) There are believed to be at least 27 human diseases
associated with genetic modifications in chromosome 22, and the
causative genes for 8 of these diseases are not yet identified.
The conditions range from cancers to disorders of fetal
development and development of the nervous system. Also, a gene
apparently involved in schizophrenia is thought to be located
within the chromosome 22 sequence, but has not yet been
identified.

5) Concerning the history of the evolution of the sequence of
human chromosome 22, we cannot yet read that history without
comparing the organization of the sequence with that of the DNA
of close animal relatives of humans, and we do not yet have this
information.

6) The author suggests that within 3 years the full sequence of
human DNA will be completed, and for the first time we will be
able to identify the 200,000 to 300,000 proteins that are used
to make a human being. But the identification of genes (and
proteins) from a sequence is not simple. Of the approximately
1000 genes on chromosome 22, only 545 are easy to spot because
they encode proteins that are similar to those previously
studied in organisms ranging from bacteria to humans. The
remaining putative genes are predicted by complex computer
modeling that is only partly accurate.

7) The author concludes: "Biology is entering a new world; not
only do we face a revolutionary leap in what we know, we also
face radical changes in the tools we must use to understand that
information. I am not sure that we are prepared for the full
impact of either but we have already made our first tentative
steps into the new world of the genome. The challenge is now to
translate the new biology into tangible benefits for humanity."

Nature 1999 402:467

Notes:

... ... *pseudogenes: The term "pseudogene" refers to a gene
bearing close resemblance to a known gene at a different locus,
but rendered nonfunctional by additions or deletions in its
structure that prevent normal expression of the gene.

Related Background:

HUMAN GENOME PROJECT AND MEDICAL SCIENCE

Francis S. Collins (National Institutes of Health, US), in a
paper presented at a recent meeting of the Massachusetts Medical
Society, points out that the history of biology "was forever
altered a decade ago by the bold decision to launch a research
program that would characterize in ultimate detail the complete
set of genetic instructions of the human being." Collins
emphasizes this is no small order, since the approximately
80,000 human genes are scattered throughout the genome "like
stars in the Galaxy, with genomic light-years of noncoding DNA
in between." The human genome contains approximately 3 billion
nucleotide base-pairs, which must be identified and sequenced.
Collins concludes: "Writing 97 years ago, Sir William Osler
described the goals of medicine this way: 'To wrest from nature
the secrets which have perplexed philosophers in all ages, to
track to their sources the causes of disease, to correlate the
vast stores of knowledge, that they may be quickly available for
the prevention and cure of disease -- these are our ambitions.'
The Human Genome Project, with its audacious goal of providing
the tools to uncover the hereditary factors in virtually every
disease, has become a major modern component of Osler's vision.
The genetic revolution in medicine is under way."

New Engl. J. Med. 341:28

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19. ON RESONANCE-INDUCED PACEMAKERS

P. Parmananda et al (National Institute of Advanced Industrial
Science and Technology, JP) discuss wave propagation in
excitable media, the authors making the following points:

1) Wave propagation in excitable media provides an example of
spatiotemporal self-organization, and target wave fronts have
been observed in both biological and chemical systems. The
underlying mechanisms for the inception of these patterns are of
practical interest, since they provide insight into relevant
problems such as ventricular tachycardias. For example,
paroxysmal starting and stopping of circulating waves of
activity can give rise to serious complex rhythms in the cardiac
system. Although wave propagation from a source point is
reasonably well understood, there are still unresolved questions
concerning the emergence of the pacemaker (source) regions. The
two common triggers for the emergence of pace-makers discussed
in the literature are diffusive instability and local
physicochemical inhomogeneities.

2) Inception of wave fronts in a quiescent excitable medium is
traditionally achieved via a large stimulus provided to an
accessible control parameter. This usually involves
parametrically crossing the bifurcation point separating the
homogeneous and oscillatory states. The authors report a new
mechanism for creating pacemakers capable of inducing
spontaneous pattern formation in a steady state. Instead of
suprathreshold perturbation with a large amplitude, small
amplitude modulation of a control parameter with an appropriate
tuning frequency is used (bifurcation point in parameter space
of the autonomous system is not crossed). For this class of
organizing centers, the quiescent excitable system, upon
inspection, abruptly starts exhibiting wave propagation without
the mandatory large amplitude parameter gradient between the
pacemaker region and the surrounding environment. Spontaneous
(abrupt) spatio-temporal self-organization of a quiescent
excitable medium in the absence of known factors such as random
concentration fluctuations and physical defects could be
attributed to such pacemakers.

3) In summary, the authors demonstrate that traveling wave
fronts can be triggered and maintained via local periodic
modulations of an appropriate system parameter. For a finite
range of perturbation frequencies, this new class of pacemakers
introduces spatiotemporal self-organization in an otherwise
quiescent medium. Excitation waves of activity similar to those
observed in heart tissue cultures and other biological
preparations can emerge in the presence of these pacemakers.

References (abridged):

1. A.T. Winfree, J. Theor. Biol. 138, 353 (1989).

2. J. D. Murray, Mathematical Biology (Springer, New York, 1989).

3. N. Shibata, P. Chen, E.G. Dixon, P.D. Wolf, N. D. Daienely,
W. M. Smith, and R. E. Idekar, Am. J. Physiol. 255, H891 (1988).

4. Jorge M. Davidenko, Paul Kent, and Jose Jalife, Physica
(Amsterdam) 49D, 182 (1991).

5. A. N. Zaikin and A. M. Zhabotinsky, Nature (London) 255, 535
(1970).

Phys. Rev. Lett. 2001 87:238302

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20. DIFFUSION IN GLASSES AND SUPERCOOLED LIQUIDS

In general, "ergodicity" is a property of dynamic systems
containing a random variable (stochastic systems): a system is
said to be ergodic if it tends in probability to a limiting form
which is independent of the initial conditions. The term "mode
coupling theory" (MCT) refers to a theory that describes the
transition of super-cooled liquids to a non-ergodic state. The
transition of the super-cooled liquid to the glass state
represents a critical slowing down of the particle motions,
leading to structural arrest. A characteristic property of the
arrested state is that it has the static structure of a liquid.
Apart from the parameters describing the microscopic motion, the
static structure factor is the only input to the theory, which
aims to give a complete description of the dynamical properties
of the system.

H.R. Schober (Institute for Solid-State Research Julich, DE)
discusses diffusion in glasses, the author making the following
points:

1) Diffusion in glasses and their melts has been studied
intensively for many years. These efforts are stimulated both by
the technological importance of glassy and amorphous materials
and by the desire to understand the physics of disordered
systems in general and the liquid to glass transition in
particular. Despite this effort there is still no agreement on
the nature of diffusion on an atomic level or on its change at
temperatures near the glass transition. This  holds even for
simple densely packed glasses such as binary metallic glasses.

2) In a hot liquid, diffusion is by flow, whereas, in the glass
well below the transition temperature, it will be mediated by
hopping processes. One key question is the transition between
the two regimes. For fragile glasses, such as most polymers and
amorphous metallic glasses, so-called "mode coupling theory"
predicts an arrest of the homogeneous viscous flow in the
undercooled melt at a temperature (Tc) well above the glass
transition temperature. Hopping processes will suppress the
predicted singularities and will become the dominant diffusion
process near Tc.

3) The nature of the hopping process is another issue of
controversy. Is it by a vacancy mechanism, similar to diffusion
in the crystalline state, or is it via a collective process
inherent to the disordered structure? Investigations are
hampered by the fact that glasses are thermodynamically not in
equilibrium, and one observes aging of the system. The diffusion
coefficient of a glass that has been relaxed for a long time
will be considerably lower than the diffusion coefficient of an
“as quenched” glass.

4) The author reports a molecular dynamics simulation involving
a calculation of the pressure dependence of the diffusion
coefficient in a binary Lennard-Jones glass (i.e., a system
described by a Lennard-Jones potential approximation). Four
temperature regimes are observed. The apparent activation volume
drops from high values in the hot liquid to a plateau value. It
rises steeply near the critical temperature of mode coupling
theory, but in the glassy state one finds again small values
similar to those in the liquid. The peak of the activation
volume at the critical temperature is in agreement with the
prediction of mode coupling theory.

References (abridged):

1. H. Mehrer, Defect Diffus. Forum 129-130, 57 (1996).

2. W. Frank, Defect Diffus. Forum 143-147, 695 (1997).

3. Y. Loirat, J.L. Bocquet, and Y. Limoge, J. Non-Cryst. Solids
265, 252 (2000).

4. F. Faupel, K. Ratzke, H. Ehmler, P. Klugkist, V. Zollmer, C.
Nagel, A. Rehmet, and A. Heesemann, Mater. Res. Soc. Symp. Proc.
664, L2.1.1 (2001).

5. F. Faupel, W. Frank, M.-P. Macht, H. Mehrer, V. Naundorf, K.
Ratzke, S.K. Sharma, H.R. Schober, and H. Teichler, Rev. Mod.
Phys. (to be published).

Phys. Rev. Lett. 2002 88:145901

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21. ON THE PROBLEM OF PREDICTABILITY IN SOLID-STATE SYNTHESIS

D. Fischer and M. Jansen (Max Planck Institute of Solid State
Research Stuttgart, DE) discuss solid state synthesis, the
authors making the following points:

1) Preparative solid-state chemistry is basically explorative in
nature, and suffers from a peculiar lack of predictability. This
constitutes a marked contrast to most fields of molecular
chemistry, in particular organic synthesis, where currently
complicated and large molecules are accessible in directed
syntheses. The fundamental difference between solid-state and
molecular syntheses is basically related to one particular
complex issue, the transport of the reacting species.
Conventional solid-state synthesis is based on reacting solid
reactant phases that, even after intense milling, are dispersed
on a macroscopic scale compared to atomic distances, and thus
reactions of solids are characterized by transport lengths of 1
to 10 microns. This is even more crucial when one recalls that
the diffusion coefficients in the solid state typically range
from 10^(-16) to 10^(-12) square centimeters per second. These
values are lower, or higher, respectively, by many orders of
magnitude for reactions between molecules, reactions which as a
rule are performed in homogeneous liquid or gaseous solutions.

2) As a consequence, solid-state reactions require a high
thermal activation, favoring thermodynamic control and thus
formation of thermodynamically stable products that represent
the global minimum of free enthalpy of the system under
investigation at the given variables of state. Furthermore, due
to the key role of transport properties, a solid's reactivity
depends not only on its chemical identity but quite crucially on
the number and size of the lattice defects present, and thus on
its pretreatment. These facts, though having always been taken
into account during conventional solid-state syntheses, e.g., by
employing specially activated reactants, significantly hamper
reproducibility and predictability in solid-state chemistry.

References (abridged):

1. DiSalvo, P. J. Science 1990, 247, 649.

2. Jansen, M. Nordrhein-Westfdtische Akademie der Wissenschaften
1996, N420.

3. Schon, J. C.; Jansen, M. Angew. Chem. 1996, /OS, 1358; Angew.
Chem., Int. Ed. Engl. 1996, 35, 1286.

4. Corey, E. J. Angew. Chem. 1991, 103, 469; Angew. Chem., Int.
Ed. Engl. 1991, 30, 455.

5. Nicolaou, K. C.; Jim Li Angew. Chem. 2001, 113, 4394; Angew.
Chem., Int. Ed. Engl. 2001, 40. 4264.

J. Am. Chem. Soc. 2002 124:3488

Also:

Ex Link: Notes on Solid-State Reactions

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22. ON CONTROLLING CRYSTAL MORPHOLOGY

N.E. Kelly et al (University of Birmingham, UK) discuss the
control of crystal morphology, the authors making the following
points:

1) To explore several properties of crystalline solids and to
exploit certain of their applications, it is often crucial to
obtain single crystals of the material with a specific desired
shape (morphology). However, the crystal morphology produced
spontaneously by normal crystal growth procedures is often not
the required morphology, and in such cases experimental
strategies must be devised to bias the crystal growth toward the
desired morphology. In principle, mechanical techniques could be
used either to constrain the preferred directions of growth or
to change the morphology after crystal growth, although such
approaches may introduce additional problems, not least the
introduction of stresses within the crystals. An alternative
strategy is to understand the molecular mechanisms that govern
the crystal growth process and to devise techniques to produce
the desired crystal morphology by altering aspects of these
mechanisms at the molecular level.

2) In general, crystal growth is governed by kinetic factors,
and the observed crystal morphology reflects the relative rates
of growth of the crystal in different directions. To alter the
crystal morphology, additive molecules (crystal growth
inhibitors) may be introduced to interact selectively with
certain crystal faces such that the growth of these crystal
faces is inhibited. The choice of inhibitor molecule depends on
the chemical nature (e.g., the types of functional group) and
the structure (i.e., the arrangement of these functional groups)
of each crystal face, such that the inhibitor molecule interacts
in a selective manner with different crystal faces.

3) The authors report a general strategy for controlling the
crystal morphology of solid inclusion compounds that have tunnel
host structures, allowing the controlled preparation of crystals
with specific morphologies within the broad spectrum ranging
from long needle crystals to flat plate crystals. The authors
have applied this strategy to urea inclusion compounds as a
prototypical example of tunnel inclusion compounds.

References (abridged):

1. Addadi, L.; Berkovitch-Yellin, Z.; Weissbuch, I.; Van Mil,
J.; Shimon, L. J. W.: Lahav, M.; Leiserowitz, L. Angew. Chemie,
Int. Ed. Engl. 1985, 24, 466.

2. Weissbuch, I.; Addadi, L.; Lahav, M.: Leiserowitz, L. Science
1991, 253, 637.

3. Heywood, B. R.; Mann, S. Adv. Mater. 1994, 6, 9.

4. Weissbuch, I.; Popovitz-Biro, R.; Lahav. M.; Leiserowitz. L.
Acta Crystallogr. 1995, B51, 115.

5. Davey, R. J.: Black, S. N.; Logan, D.; Maginn, S. J.;
Fairbrother, J. E.; Grant, D. J. W. J. Chem. Soc.. Faraday
Trans. 1992. 88, 3461.

J. Am. Chem. Soc. 123:12682

Related Background:

ON THE PREDICTION OF CRYSTAL STRUCTURE

J. Pillardy et al (Cornell University, US) discuss crystal
structure prediction, the authors making the following points:

1) Crystal structure prediction is one of the most challenging
and important problems in theoretical and applied crystal
chemistry. It plays an extremely important role in fields in
which the rational design of new organic solids is involved
(e.g., pharmaceuticals, explosives, pigments, photosensitive and
optoelectronic materials, etc.), and it is also of significance
in solving problems of crystal polymorphism.

2) Despite much effort by many research groups during the past
20 years, the general problem of crystal structure prediction is
far from being solved. Generally, the term "crystal structure
prediction" is understood to refer to a search for the most
thermodynamically and kinetically favorable crystal structures
for a given molecular composition without using any experimental
information. (In many cases, however, experimental data are
included implicitly in the force field or taken into
consideration by conducting the search in the most common
crystal space groups).

3) Unfortunately, no theoretical methods capable of taking into
account the kinetic factors (conditions of nucleation and
growth, nature of solvent, etc.) have been developed. Therefore,
crystal structure prediction is currently based solely on
thermodynamic considerations coupled with the assumption that
the structure observed experimentally corresponds to the global
minimum of the free energy. However, free energy is not a
function of geometrical coordinates of a single crystal
structure. Therefore, the traditional approach to crystal
structure prediction assumes that the free energy of a crystal
can be approximated by its potential energy (which can be
computed easily), with the lowest minima corresponding to the
structures observed experimentally. In both theory and practice,
this is a far from satisfactory compromise.

Proc. Nat. Acad. Sci. 2001 98:12351

Related Background:

ON CRYSTAL POLYMORPHISM

C.A. Mitchell et al (Eli Lilly & Co., US) discuss crystal
polymorphism, the authors making the following points:

1) In this context, the term "polymorphism" refers to the
ability of a molecule to adopt different crystal forms. Crystal
polymorphism reflects the delicate balance of forces responsible
for guiding molecular organization in the solid state. Though
often viewed as an annoyance, this phenomenon represents an
opportunity to examine subtle structure-property relationships
and the relationship between molecular conformation and crystal
packing. An elucidation of polymorphism promises molecular-level
control of crystallization and improvement in crystal structure
design and prediction.

2) Polymorphism also has considerable technological significance
owing to the dependence of crystal properties on solid-state
structure. For example, the discovery and characterization of
the polymorphs of a drug are important for evaluation of shelf
stability (against transformations to other polymorphs) and
bioavailability of the final pharmaceutical product. Polymorph
screening is a particularly important component of drug
development processes because of patent protection of new
crystal forms, regulations that require polymorph identification
and characterization, and the need for strict monitoring and
recording of process conditions to achieve controlled and
reproducible crystallization outcomes.

3) Despite decades of polymorphism studies, prediction of all
possible polymorphs of a given substance remains difficult.
Furthermore, it is impossible to guarantee that all experimental
parameters that could lead to the discovery of unknown forms
have been exhausted or that polymorphs produced through an
ostensibly reliable process will not disappear at a later time.

J. Am. Chem. Soc. 2001 123:10830

Related Background:

POLYMORPHISM IN CRYSTALS

In general, in this context, the term "polymorphism"
(pleomorphism) refers to the crystallization of a chemical
substance into two or more forms having different structures,
for example, diamond and graphite.

... ... H. Liu et al (North Carolina State University, US)
discuss polymorphism in crystals. Understanding the factors that
control polymorphism is important for the rational design and
synthesis of crystalline materials that exhibit targeted
physical properties, just as control of isomerism, for example,
is critical in natural product synthesis. In biology, only
L-amino acids are used in protein synthesis, and the enzymes
that catalyze the reactions do not recognize the D-enantiomers.
Similarly, in solid-state chemistry, two polymorphs of a
material frequently exhibit dramatically different properties.
For example, silicon carbide crystallizes in numerous
polymorphs, the most common polymorph widely utilized as the
abrasive called carborundum, whereas another polymorph is
suitable for blue-light emitting diodes. In the absence of a
mechanistic understanding, reaction design to achieve desired
products is only an empirical endeavor. While a detailed
understanding of organic reaction mechanisms is of fundamental
importance to the modern pharmaceutical industry, a mechanistic
understanding of solid- state chemistry is still in its infancy.
Increasingly, measurements of the kinetics and thermodynamics of
solid-state phase transitions in bulk solids and nanoparticles
have been reported, but microscopic descriptions of the atomic
motions involved, particularly where bonds are broken or formed,
are rarely presented.

J. Am. Chem. Soc. 2001 123:7564

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23. ON SHAPE CONTROL OF MACROMOLECULES

S.S. Sheiko and M. Moeller (University of Ulm, DE) discuss shape
control of macromolecules, the authors making the following
points:

1) The size and complexity of the structure of macromolecules
allows the combination of different, in some cases even
antagonistic, properties, e.g., solubility, flexibility, or
electronic properties. The control of the connectivity of
molecular subunits can be used to transform short-range
interactions into complex long-range structural organization.
Biomacromolecules demonstrate how single polymer molecules and
their ensembles can serve as functional nano-objects. While
functional properties such as catalytic activity, directed
motion, and energy transport are well established in the case of
biomolecules, our ability to develop synthetic molecular devices
is in its infancy, although significant efforts are directed
toward shape control and directed motion.

2) A major basis for progress in producing macromolecular
functionality is an improved ability to control macromolecular
and supramolecular structures in great detail. Dense and
cascade-type branching provide access to 3-dimensional molecules
that do not interpenetrate but interact via their surfaces.
Recent synthetic developments include microgels, dendrimers, and
arborescent graft polymers. Polymerization of substituted
monomers as well as graft polymerization from a linear chain can
yield cylindrically shaped macromolecules such as "hairy rods",
wormlike brushes, and monodendron-jacketed chains. Advances in
the control of primary molecular structure and advances in
manipulation techniques for molecular conformation of such
hyperbranched molecules make them intriguing building units for
nanoscopic devices, biochemical sensors, molecular containers,
templates for nanolithography, energy transfer funnels, and
polyfunctional initiators and catalysts.

3) Shape control and the development of shape-responsive
molecules also relies on the availability of analytical tools
that provide spatial resolution down to subnanometer scale,
strong contrast with respect to the chemical composition and
physical properties, sensitivity to molecular forces in the
piconewton range, and in-situ monitoring of molecular motion and
conformation with a time resolution down to and even below
milliseconds. Molecular probes, such as optical or magnetic
tweezers, micropipets, and microfibers, have been developed to
manipulate single molecules and to measure their response to
mechanical actions such as stretching, torsion, and compression.
A force resolution down to 0.1 piconewtons has enabled
quantitative measurement of molecular forces and has provided
new information concerning the basic principles of folding,
motion, and interactions of individual molecules.

References (abridged):

1. Stayton, P. S.; Shimoboji, T.; Long, C.; Chilkoti, A.; Chen,
G.; Harris, J. M.; Hoffman, A. S. Nature 1995, 378, 472.

2. Mao, C.; Sun, W.; Shen, Z.; Seeman, N. Nature 1999, 397, 144.

3. Montemagno, C.; Bachand, G.; Stelick, S.; Bachand, M.
Nano-technology 1999, 19, 225.

4. Noji, H.; Yashuda, R.; Yoshida, M.; Kinosita, K., Jr. Nature
1997, 386,299.

5. Dennis, J. R.; Howard, J.; Vogel, V. Nanotechnology 1999, 19,
232.

Chem. Rev. 2001 101:4099

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24. SURFACE PHASE TRANSITION TEMPERATURES

Liquid crystals can be considered a 4th phase of matter, a state
qualitatively different from the ordinary 3 phases, gas, liquid,
and solid. Liquid crystals flow like a liquid, but there is
order in at least one dimension in the arrangement of the
molecules. "Nematic crystals" are liquid crystals with long
molecules all aligned in the same direction. "Cholesteric" and
"smectic" liquid crystals have molecules arranged in distinct
layers: in cholesteric crystals, the axes of the molecules are
parallel to the plane of the layers; in smectic crystals, the
axes of the molecules are perpendicular to the plane of the
layers. A liquid-crystal polymer is a polymer with a self-
organized liquid crystal structure that combines strength with
lightness.

K.S. Gautam and A. Dhinojwala (University of Akron, US) discuss
surface phase transition temperatures, the authors making the
following points:

1) Considerable effort has been focused on understanding whether
surface phase transition temperatures are different from those
in the bulk. It is expected that surfaces will melt at a lower
temperature than the bulk, and this has been experimentally
observed for almost all solids studied. However, small molecules
that have a basic building block of linear alkyl chains, such as
n-alkanes and alcohols, exhibit surface freezing, where the
surfaces show existence of ordered crystalline phases above the
bulk melting temperature. In the case of liquid crystals,
smectic surface layers are observed at the vapor-nematic or
vapor-liquid interfaces.

2) The authors report that when alkyl chains are chemically
linked to polymer backbones, the influence of interfaces on
melting transitions is much stronger than that observed
previously for small molecules. The authors observe two sharp
transitions above the bulk melting temperature at the
polymer/air interface. The first transition is associated with
melting of side chains to a stable smectic-like ordered state.
This ordered state persists 10 to 20 degrees Celsius above the
bulk melting temperature, beyond which a second transition to
the isotropic state is observed. The presence of an additional
surface phase at the polymer/air interface that does not exist
in the bulk has not been observed before for small molecule
n-alkanes, alcohols, and liquid crystals. In contrast, at the
polymer/sapphire interface, the authors observe a single
transition from crystalline to disordered state near the bulk
melting temperature (for 18 carbon polymer side chain length).
The authors suggest these observations have direct technological
consequences for the use of long alkyl or fluorinated side chain
polymers for smart adhesives, release coating, and soil
resistance coating applications.

References (abridged):

1. M. Faraday, Proc. R. Soc. London 10, 440 (1860).

2. J. Als-Nielsen, F. Christensen, and P. S. Pershan, Phys. Rev.
Lett. 48, 1107 (1982).

3. J. W. M. Frenken and J. F. van der Veen, Phys. Rev. Lett. 54,
134 (1985).

4. D.-M. Zhu and J.G. Dash, Phys. Rev. Lett. 57, 2959 (1986).

5. S. Chandavarkar, R. M. Geertman, and W. H. de Jeu, Phys. Rev.
Lett. 69, 2384 (1992).

Phys. Rev. Lett. 2002 88:145501

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25. IN FOCUS: ON MAGNETISM IN SOLIDS

"Magnetism in solids arises on a local scale through quantum
mechanical exchange among electrons of neighboring atoms. In
ferromagnets, the exchange favors parallel electron spins, and
the spatial magnetic structure can range from wonderfully
simple--a uniformly magnetized sample--to woefully complex.
Except for special sample shapes, uniform magnetization carries
a magnetostatic cost in terms of the energy associated with the
long-range interaction between dipoles. The energy can be
minimized if the dipoles are not all parallel, hence the
formation of magnetic domains. Anisotropy effects that favor the
orientation of magnetization along certain crystallographic
directions further complicate the situation. The essence of this
competition is summarized by so-called "exchange lengths," which
dictate the minimum scale on which important variations in the
direction of magnetization can occur and are often in the
nanometer range. In the nonequilibrium regime, the presence of
excess energy leads to additional complication including
nucleation and growth of domains, propagation of spin-wave
excitations on very short wavelengths, and generation of
magnetostatic modes akin to the vibrations of a drumhead. The
most successful model of this physics is classical (treating
small volumes of material as big magnetic moments) and
phenomenological: it is hand-built and constructed to follow
reasonable guiding principles such as conserving the magnitude
of the big moments, allowing only their directions to change.
Only now are the tools becoming available to fully test this
description against the complex behavior that can occur even in
microscopic specimens and point the way toward improvements. A
fully quantum-mechanical treatment of these problems remains
intractable, but we can now perform experiments sufficiently
detailed and controlled that some might regard them as 'analog
computations.'"

M.R. Freeman and B.C. Choi: Science 2001 294:1484

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