ScienceWeek

ScienceWeek - June 7, 2002 Vol. 6 Number 23

An Online Research Digest Published Weekly Since 1997

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There is nothing like astronomy to pull the stuff out of man.
His stupid dreams and red-rooster importance: let him count the
star-swirls.
-- Robinson Jeffers (1887-1962)

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Top Graphic: Woman on a Blue Divan
-- Ernest Kirschner (1880-1938)

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Section 1

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

1. On Isotope Tracking of Bird Migration 

2. Calcium Currents and Circadian Rhythms of Neurons 

3. Ions and Sperm Motility 

4. On the Movement of Glacial Ice Sheets 

5. Evidence for Early Chloroplast Acquisition by Eukaryotes 

6. Pattern Formation in Cell Populations 

7. Behavior of Water in a Janus Interface

8. On the Hydrophobic Effect

9. On the Cosmological Constant: A New Limit

10. On Solid-State Convection of Earth's Lower Mantle 

11. Aerosols and Cloud Microphysics

12. On Clustered Star Formation 

13. On Tuberculosis in New York 1990-1999 

14. Alzheimer's Disease: Incidence, Prevalence, and Economic
Impact 

15. On Automobile Traffic Crashes

16. History of Anthrax as a Biological Weapon 

17. Health Effects of Ground-Level Ozone 

18. Smoking: Years of Life Lost and Economic Costs 

19. Relaxation Mechanisms in Strained Nanoislands

20. On In Vitro Selection of Functional Proteins 

21. On Silicon-Based Quantum Computer Architecture 

22. On Water-Soluble Block Copolymers 

23. On Conjugated Polymer Interfaces 

24. Quantum Cryptography: On Private Quantum Entanglement over
Arbitrary Distances 

25. In Focus: On the Strong and Weak Forces 

26. ScienceWeek Notices and Subscription Information

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Section 2

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1. ON ISOTOPE TRACKING OF BIRD MIGRATION

Keith A. Hobson (Canadian Wildlife Service, CA) discuss tracking
of bird migration, the author making the following points:

1) The most baffling and complex phenomena in nature are
sometimes unraveled by the simplest experiments. Tracking the
migrations of different populations of a particular mammal or
bird over vast geographical ranges and calculating whether the
populations intermix has proven intractable for all but the most
conspicuous of species. For migratory birds that breed annually
in North America and Europe and migrate to more southerly
wintering grounds, conventional marking methods are woefully
inadequate for deciphering the mystery of their movements. The
task is even more formidable for very small organisms such as
migratory insects.

2) Across continents, there are often predictable patterns in
the abundance of naturally occurring stable isotopes such as
carbon (C-13), hydrogen (H-2 deuterium), sulfur (S-34), and
strontium (Sr-87). Of particular value is the abundance of H-2
in rainfall, which has a characteristic latitudinal and
continental distribution. H-2 is taken up by birds in their food
and water and becomes deposited in feathers and other
metabolically inactive tissues. Most migratory birds grow new
feathers before migration. Thus, the approximate latitude at
which a bird's migration started can be readily calculated by
measuring the ratio of H-2 to normal hydrogen in a single
feather. This approach enables delineation of large-scale
population structures in small migratory animal populations (1).

3) Continental distribution patterns of isotopes in rainfall
were established decades ago by isotope hydrologists. Indeed,
botanists have spent years analyzing patterns of C-13
distribution in plants resulting from climatic, altitudinal, and
photosynthetic factors. Cormie and colleagues (2) were among the
first to show that continental patterns of isotopes in rainfall
pass from surface waters into plants and ultimately into
herbivores. Given that insectivorous birds are a step above
herbivores in the food chain, it comes as no surprise to find
that rainfall isotope signatures are also present in birds'
feathers. This discovery has prompted a major breakthrough in
avian migration tracking (3). In contrast to traditional
capture-recovery methods, isotope tracking only requires
knowledge of the distribution of isotope abundance across the
geographical range of the target organism. Hence, every isotope
measurement after capture becomes a recapture because, like
bands, rings, or other markers, the target organism's tissues
contain information about its place of origin. With this
strategy, investigators are freed from the "needle in a
haystack" dilemma of trying to recover banded individuals at
stopover locations or on remote wintering grounds.

References (abridged):

1. D. R. Rubenstein et al., Science 295, 1062 (2002).

2. A. B. Cormie, H. P. Schwarcz, J. Gray, Geochim. Cosmochim.
Acta 58, 365 (1994)

3. K. A. Hobson, L. I. Wassenaar, Oecologia 109, 142 (1997).

Science 2002 295:981

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2. CALCIUM CURRENTS AND CIRCADIAN RHYTHMS OF NEURONS

In biology, a "circadian rhythm" is a daily cyclical process, be
it biochemical, or physiological, or behavioral. The human
sleep-wake cycle is the most familiar example. Circadian rhythms
are often described in terms of endogenous "biological clocks",
with the thrust of research to reduce some particular behavioral
or physiological circadian rhythm to biochemical events. These
clocks are usually set by environmental cues such as the
light-dark cycle, and what is characteristic of an endogenous
clock is that if one removes the environmental cue, keeps the
organism in constant light, for example, the endogenous rhythm
will continue, but will tend to drift out of phase with the
outdoors environmental light-dark cycle. Restoring the external
light-dark cue will reset the clock to its normal intrinsic
rhythm.

The hypothalamus is a deep brain center prominently involved in
the functions of the autonomic (visceral motor) nervous system
and, through its vascular link with the anterior lobe of the
hypophysis (pituitary gland), in endocrine mechanisms; it also
appears to play a role in neural mechanisms underlying moods and
motivational states. The suprachiasmatic nucleus is a cluster of
nerve cells in the hypothalamus.

C.M. Pennartz et al (Netherlands Institute for Brain Research,
NL) discuss circadian rhythms of neurons, the authors making the
following points:

1) It has long been known that neurons in the suprachiasmatic
nucleus transmit circadian output to other brain areas by
diurnal modulation of their spontaneous discharge frequency
(1-5). When firing activity of suprachiasmatic nucleus neurons
is monitored in cultures of dissociated cells, many of them
express a circadian rhythm that is asynchronous with that of
other cells, indicating the cell-autonomous nature of the
oscillator (4). The molecular loops operating within clock cells
involve transcription, translation and negative protein-mediated
feedback on gene expression (5). Much less is known about the
signals by which the core loop communicates with ionic channels
and transporters in the plasma membrane, which directly regulate
membrane excitability. Ionic channels may be under direct
transcriptional control of the core loop or, alternatively, may
be regulated by as-yet unidentified clock-controlled genes (5).

2) A principal step in the elucidation of this problem is to
dissect the ionic mechanisms by which the circadian message from
the molecular clock is transduced into bioelectric output. This,
however, is not a simple problem. First, there are many ionic
currents in the suprachiasmatic nucleus that may be targeted by
the molecular clock, yet their contribution to spontaneous
firing is largely unknown. Second, ionic currents in
suprachiasmatic nucleus neurons can be monitored by patch-clamp
recordings for several hours, which is, however, too short to
study circadian modulation within a single neuron. This
technical limitation necessitates groupwise comparisons between
neurons recorded during different circadian phases. This
consideration, combined with the finding that clock cells become
desynchronized in dissociated-cell cultures4, led the authors to
use acutely prepared brain slices in studying diurnal modulation
of ionic conductances.

3) The authors report a demonstration of a diurnal modulation of
Ca2+ current in suprachiasmatic neurons. This current strongly
contributes to the generation of spontaneous oscillations in
membrane potential, which occur selectively during daytime and
are tightly coupled to spike generation. Thus, day–night
modulation of Ca2+ current is a central step in transducing the
intracellular cycling of molecular clocks to the rhythm in
spontaneous firing rate.

References (abridged):

1. Inouye, S.-I. T. & Kawamura, H. Persistence of circadian
rhythmicity in a mammalian hypothalamic "island" containing the
suprachiasmatic nucleus. Proc. Natl Acad. Sci. USA 76, 5962-5966
(1979)

2. Green, D. J. & Gillette, R. Circadian rhythm of firing rate
recorded from single cells in the rat suprachiasmatic brain
slice. Brain Res. 245, 198-200 (1982)

3. Schwartz, W. J., Gross, R. A. & Morton, M. T. The
suprachiasmatic nuclei contain a tetrodotoxin-resistant
circadian pacemaker. Proc. Natl Acad. Sci. USA 84, 1694-1698
(1987)

4. Welsh, D. K., Logothetis, D. E., Meister, M. & Reppert, S. M.
Individual neurons dissociated from rat suprachiasmatic nucleus
express independently phased circadian firing rhythms. Neuron
14, 697-706 (1995)

5. Reppert, S. M. & Weaver, D. R. Molecular analysis of
mammalian circadian rhythms. Annu. Rev. Physiol. 63, 547-676
(2001)

Nature 2002 416:286

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3. IONS AND SPERM MOTILITY

In this context, the term "teleost" refers to a large and
extremely diverse group of ray-finned fishes. The teleosts
include virtually all of the world's important sport and
commercial fishes, as well as a much larger number of lesser
known species. The group comprises some 20,000 species (about
equal to all other vertebrate groups combined), with new species
being discovered each year.

In this context, the term "hyperpolarization" refers to an
increase in the resting membrane potential difference across a
cell membrane

C.A. Vines et al (University of California Davis, US) discuss
ions and sperm motility, the authors making the following points:

1) Teleost fish sperm are quiescent within the testes and
seminal plasma before spawning, but most initiate motility after
dilution into the external medium (freshwater or seawater for
most species) in which spawning occurs (1). In salmonids,
motility initiation occurs with dilution in freshwater,
specifically from a reduction in extracellular potassium that
drives a membrane hyperpolarization and an increase in
intracellular calcium Ca2+ (2-5). Changes in the concentrations
of specific ions (Ca2+, K+, and possibly Na+ and Cl-) also have
been linked to motility initiation in Atlantic croaker sperm. A
hyperpolarization of the sperm membrane also has been documented
in carp sperm, reportedly linked to the opening of voltage-gated
Ca2+ channels and an increase in intracellular Ca2+. In other
freshwater teleost sperm (goldfish, zebra fish), as well as in
marine teleost sperm (puffer, flounder), motility is believed to
occur as a result of nonspecific hypo- or hyperosmotic changes
that drive changes in intracellular ion concentrations (5).
Thus, in all systems studied to date, a membrane
hyperpolarization leads to an increase in intracellular Ca2+ and
the initiation of motility.

2) Sperm of the Pacific herring, Clupea pallasi, are unique in
that they are immotile upon spawning in the environment. Herring
sperm have evolved to remain motionless for up to several days
after spawning, yet are still capable of fertilizing eggs. An
egg chorion ligand termed "sperm motility initiation factor"
(SMIF) induces motility in herring sperm and is required for
fertilization.

3) The authors report that SMIF induces calcium influx, sodium
efflux, and a membrane depolarization in herring sperm. Sperm
motility initiation by SMIF depended on decreased extracellular
sodium (<350 mM) and could be induced in the absence of SMIF in
very low sodium seawater. Motility initiation depended on 1 mM
extracellular calcium. Calcium influx caused by SMIF involved
both the opening of voltage-gated calcium channels and reverse
sodium-calcium (Na+/Ca2+) exchange. Membrane depolarization was
slightly inhibited by a calcium channel blocker and markedly
inhibited by a Na+/Ca2+ exchange inhibitor. Sodium efflux caused
by SMIF-initiated motility was observed when using both
extracellular and intracellular sodium probes. A Na+/Ca2+
exchange antigen was shown to be present on the surface of the
sperm, primarily over the midpiece, by using an antibody to the
canine Na+/Ca2+ exchanger. This antibody recognized a 120-kDa
protein that comigrated with the canine myocyte Na+/Ca2+
exchanger.

4) The authors conclude that sperm of Pacific herring are now
demonstraed to use reverse Na+/Ca2+ exchange in motility
initiation. The authors suggest this mechanism of regulation of
motility initiation may have evolved for both maintenance of
immotility after spawning as well as ligand-induced motility
initiation.

References (abridged):

1. Morisawa, M. (1994) Zool. Sci. 11, 647-662

2. Gatti, J.-L. , Billard, R. & Christen, R. (1990) J. Cell.
Physiol. 143, 546-554

3. Boitano, S. & Omoto, C. K. (1991) J. Cell Sci. 98, 343-349

4. Tanimoto, S. , Kudo, Y. , Nakazawa, T. & Morisawa, M. (1994)
Mol. Reprod. Dev. 39, 409-414

5. Darszon, A. , Labarca, P. , Nishigaki, T. & Espinosa, F.
(1999) Physiol. Rev. 79, 481-510

Proc. Nat. Acad. Sci. 2002 99:2026

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4. ON THE MOVEMENT OF GLACIAL ICE SHEETS

M.J. Siegert et al (University of Bristol, UK) discuss the
movement of glacial ice sheets, the authors making the following
points:

1) Ice is, of course, a solid, but it deforms very slowly when a
large stress is applied — such as the stress induced in an ice
sheet by its own great weight. This deformation causes a parcel
of ice within a glacier to move slowly over time. Also, a piece
of ice on the surface of an ice sheet is buried by subsequent
snowfalls, which cause it to move downward into the ice sheet at
a significant velocity with respect to the deformation. Over all
the motion tends to be down in the middle and out to the sides.
More specifically, the flow at the center of an ice sheet
radiates from the ice divide, the place where there is no
lateral movement on the surface. As the ice moves away from the
ice divide, its lateral velocity increases from an initial value
of perhaps a few meters per year. Nearer their margins, ice
sheets are effectively "drained" by fast-flowing rivers of ice,
known as ice streams. The velocity of an ice stream is typically
several hundred meters per year. These streams flow quickly
because water at the base reduces friction, allowing the ice to
slide across the underlying ground, with internal deformation
making only a small contribution to the total velocity.

2) Broadly speaking, the ice continues to flow faster and faster
until it reaches its demise in one of two ways. The ice sheet
may terminate on land (stopping because the ice at the surface
melts as fast as it is supplied) or it can terminate at sea.
Where an ice sheet flows into the ocean intact and becomes
afloat, it forms an ice shelf. Such an ice shelf loses mass by
"calving" icebergs from its edge and by melting at the bottom.
As they flow over land, ice sheets erode and entrain sediments
at their bases. They can transport this rocky material great
distances before ultimately depositing it at their margins. This
is why in front of any glacier you will see moraines, piles of
sediment resembling building rubble. After glaciers and ice
sheets melt away, moraines are left behind, providing a
geological marker of the extent of the ice in the distant past.

3) The problem of reconstructing the boundaries of an ancient
ice sheet would thus appear to be simple — just map the location
of the terminal moraines. In reality, the situation is more
complicated because in some areas terminal moraines are either
absent or are now hidden below sea level. Often several moraines
from different glacial advances are jumbled together, making the
relevant one difficult to distinguish.

References (abridged):

1. Dowdeswell, J. A., et al. 1996. Large-scale sedimentation on
the glacier-influenced polar North Atlantic margins: Long-range
side-scan sonar evidence. Geophysical Research Letters
23:3535-3538.

2. Elverhei, A., et al. 1995. The growth and decay of the Late
Weichselian ice sheet in western Svalbard and adjacent areas
based on provenance studies of marine sediments. Quaternary
Research 44:303-316.

3. Forman, S. L. et al. 1996. Postglacial emergence of western
Franz Josef Land, Russia, and retreat of the Barents Sea Ice
Sheet. Quaternary Science Reviews 15:77-90.

4. Forman, S. L., et al. 1999. Late Quaternary stratigraphy of
western Yamal Peninsula, Russia: New constraints on the
configuration of the Eurasian ice sheet. Geology 27:807-810.

5. Grosswald, M. G, and T. J. Hughes. 1995. Paleoglaciology's
grand unsolved problem. Journal of Glaciology 41:313-332.

American Scientist 2002 90:32

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5. ON EVIDENCE FOR EARLY CHLOROPLAST ACQUISITION BY EUKARYOTES

In general, prokaryote and eukaryote cells are distinguished by
the absence or presence, respectively, of internal
membrane-bound organelles, and one important question concerns
how eukaryotes acquired these organelles.

In biology, "symbiosis" is an intimate and protracted
association of individuals of different species. "Endosymbiosis"
is an arrangement in which one organism lives inside another
organism, but the term is usually restricted to arrangements of
mutual benefit, thus not including parasite-host relationships.
A number of eukaryotic cell organelles (including mitochondria)
are believed to have originated from endosymbiotic relationships
between eukaryotic cells and simpler cells.

The cell organelles called "chloroplasts" contain several
photosynthetic pigments (chlorophylls). Chloroplasts are found
in all photosynthetic plant cells, but not in photosynthetic
prokaryotes (i.e., not in cells without membrane-bound
organelles). The typical higher plant chloroplast is
lens-shaped, approximately 5 microns across the larger
dimension, and the number of chloroplasts per cell can vary from
1 to 100 depending on the type of cell. A mature chloroplast is
typically bounded by two membranes, an inner membrane and an
outer membrane, the membranes possessing significantly different
chemical constituents. In addition to a number of enzymes
involved in photosynthesis, chloroplasts also contain in their
interior a circular DNA molecule and protein synthetic machinery
typical of prokaryotes. The current consensus is that
chloroplasts may have originated from *cyanobacteria that became
endosymbionts.

Cyanobacteria are a phylum of bacteria characterized by
blue-green (cyan) photosynthetic pigments, abundant in a variety
of habitats, particularly in fresh water and soil. Cyanobacteria
are responsible for generating a large portion of the free
oxygen in the Earth's atmosphere. They apparently produced
stromatolite limestone deposits, as well as the bulk of modern
petroleum deposits. (Stromatolites are laminated calcareous
microbial fossil deposits formed principally by cyanobacteria
and algae.)

Mitochondria are double-membrane enclosed organelles of cells
that are involved with several important biochemical pathways,
including *electron transport and *oxidative metabolism. Various
types of eukaryotic cells (i.e., cells containing membrane-bound
organelles) may contain from a few to several thousand
mitochondria in each cell type. The mitochondria are relatively
large cylindrical structures up to 10 microns long and up to 2
microns in diameter, and they are believed to have originated as
organisms that became symbiotic with eukaryotic cells.

In this context, the term "plastid" refers in general to any of
various types of intracellular organelles found in plant cells.
Chloroplasts are a type of plastid. In general, each plastid is
surrounded by an envelope of two membranes. Plastids arise
either from division of existing plastids or from protoplastids
(proplastids), and plastids are believed to have originated as
endosymbionts in plant cells. Proplastids are double
membrane-bound organelles with little internal structure that
act as precursors for the development of plastids.

J.O. Andersson and A.J. Roger (Dalhousie University, CA) discuss
chloroplast acquisition by eukaryotes, the authors making the
following points:

1) Since the incorporation of mitochondria and chloroplasts
(plastids) into the eukaryotic cell by endosymbiosis [1] , genes
have been transferred from the organellar genomes to the nucleus
of the host [2–4] , via an ongoing process known as
endosymbiotic gene transfer [5] . Accordingly, in photosynthetic
eukaryotes, nuclear genes with cyanobacterial affinity are
believed to have originated from endosymbiotic gene transfer
from chloroplasts.

2) By tracing genes of mitochondrial origin in the nucleus of
amitochondrial protists, it has been shown that most if not all
amitochondrial groups are probably secondarily amitochondrial,
suggesting that the origin of mitochondria may have been
concurrent with the origin of the eukaryotic cell itself . In
contrast to mitochondria, it is generally accepted that only a
subset of eukaryotes experienced the endosymbiosis that gave
rise to present-day chloroplasts . Three lineages, Glaucophyta,
Rhodophyta, and Viridiplantae, possess primary plastids that are
thought to be derived from a single cyanobacterial endosymbiosis
in their common ancestor after their divergence from other
eukaryotic lineages. Photosynthetic plastids then spread from
these groups to other algal eukaryotes, including heterokonts,
haptophytes, dinoflagellates, cryptomonads, chlorarachniophytes,
and euglenids, by secondary or tertiary endosymbioses, whereby
photosynthetic eukaryotes were engulfed by heterotrophic hosts .
However, gain of photosynthetic chloroplasts does not
necessarily mean that they will be permanently retained in a
lineage. For example, loss of photosynthesis has occurred many
times in parasitic plants, dinoflagellates, and apicomplexan
protists, such as the malaria parasite Plasmodium falciparum,
which harbor nonphotosynthetic plastids. The possibility of
widespread secondary loss of plastid functions makes it
difficult to pinpoint the timing of the primary endosymbiotic
origin of chloroplasts within eukaryotes. Like mitochondria,
plastids could have entered eukaryotes relatively early on but
been secondarily lost multiple times in various
nonphotosynthetic eukaryotic lineages.

3) To address the timing of the chloroplast symbiosis in
eukaryote lineages, the authors selected one gene that has been
suggested to represent an endosymbiotic gene transfer, gene
"gnd", for extensive phylogenetic sampling. The authors focused
on nonphotosynthetic eukaryotic lineages that are closely
related to photosynthetic eukaryotic lineages, since they are
likely to contain genes of chloroplast origin if the chloroplast
acquisition happened earlier than previously thought.

4) The authors report their data suggest that chloroplasts were
introduced into eukaryotes much earlier than previously thought
and that several major groups of heterotrophic eukaryotes have
secondarily lost photosynthetic plastids.

References (abridged):

1. Gray M.W. (1992) The endosymbiont hypothesis revisited. Int.
Rev. Cytol., 141:233-357.

2. Martin W., Stoebe B., Goremykin V., Hansmann S., Hasegawa M.
and Kowallik K.V. (1998) Gene transfer to the nucleus and the
evolution of chloroplasts. Nature, 393:162-165.

3. Rujan T. and Martin W. (2001) How many genes in Arabidopsis
come from cyanobacteria? An estimate from, 386:protein
phylogenies. Trends Genet. 17:113-120.

4. Karlberg O., Canbaeck B., Kurland C.G. and Andersson S.G.E.
(2000) The dual origin of the yeast mitochondrial proteome.
Yeast, 17:170-187.

5. Adams K.L., Daley D.O., Qiu Y.L., Whelan J. and Palmer J.D.
(2000) Repeated, recent and diverse transfers of a mitochondrial
gene to the nucleus in flowering plants. Nature, 408:354-357.

Current Biology 2002 12:115

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6. ON PATTERN FORMATION IN CELL POPULATIONS

L. Jelsbak and L. Segaard-Andersen (University of Southern
Denmark, DK) discuss cell pattern formation, the authors making
the following points:

1) Formation of spatial patterns of cells from a mass of
initially identical cells is a recurring theme in developmental
biology. The dynamics that direct pattern formation in
biological systems often involve morphogenetic cell movements
(1-3). An example is fruiting body formation in the gliding
bacterium Myxococcus xanthus in which an unstructured population
of identical cells rearranges into an asymmetric, stable pattern
of multicellular fruiting bodies in response to starvation (4).

2) M. xanthus cells are rod shaped and move by gliding, a
process whereby a bacterial cell moves in the direction of its
long axis on a solid surface (5). Fruiting body morphogenesis
absolutely depends on starvation of cells at a high cell density
on a solid surface (4). It represents a true de novo pattern
formation process as it starts from a homogeneous and symmetric
population of starving cells, and occurs without the
contribution of external cues. In the presence of nutrients, M.
xanthus cells form cooperatively spreading swarms. In response
to starvation, swarming behavior is constrained, and, after 6
hours of starvation, small aggregates are evident. Some of these
aggregates enlarge into hemispheres as a consequence of
continued accumulation of cells, and, after 24 hours,
haystack-shaped fruiting bodies have formed, each containing
approximately 100.000 densely packed cells. Within the nascent
fruiting bodies, the motile, rod-shaped cells differentiate into
non-motile spores. Aggregates that do not mature into fruiting
bodies dissipate as their cells migrate to other aggregation
centers. Before the appearance of aggregation centers, cells
become organized in streams, in which the cells are arranged
end-to-end and with their long axes roughly in parallel with
each other, and cells move toward the aggregation centers
organized in these streams.

3) Aggregation is induced by the cell surface-associated
"C-signal", the latest acting of several extracellular signals
required for fruiting body morphogenesis. The C-signal is a cell
surface-associated protein encoded by the csgA gene. Cells that
carry mutations in the csgA gene are conditionally defective in
aggregation and sporulation.

4) The authors propose that C-signal transmission is a local
event involving direct contacts between cells that results in a
global organization of cells, and that the pattern formation
mechanism does not require a diffusible substance or other
actions at a distance. Rather it depends on contact-induced
changes in motility behavior to direct cells appropriately.

References (abridged):

1. Le Douarin, N. M. (1984) Cell 38, 353-360

2. De Felici, M. , Dolci, S. & Pesce, M. (1992) Int. J. Dev.
Biol. 36, 205-213

3. Melchers, F. , Rolink, A. G. & Schaniel, C. (1999) Cell 99,
351-354

4. Dworkin, M. (1996) Microbiol. Rev. 60, 70-102

5. Spormann, A. M. (1999) Microbiol. Mol. Biol. Rev. 63, 621-641

Proc. Nat. Acad. Sci. 2002 99:2032

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7. BEHAVIOR OF WATER IN A JANUS INTERFACE

X. Zhang et al (University of Illinois Urbana, US) discuss Janus
interfaces, the authors making the following points:

1) The role of water as a solvent or lubricant in physical
situations from biology to geology is almost universally thought
to be important, but the details are disputed (1-5). In
proteins, for example, the side chains of roughly half the amino
acids are polar whereas the other half are hydrophobic; the
nonmixing of the two is a major mechanism steering the folding
of proteins and other self-assembly processes. Similarly, it is
an everyday occurrence to observe the beading-up of raindrops,
on raincoats or the leaves of plants. Moreover, it has been
observed theoretically and experimentally that when the gap
between two hydrophobic surfaces becomes critically small, water
is spontaneously ejected, whereas water films confined between
symmetric hydrophilic surfaces are stable at comparable spacings
(3). It is thus interesting to consider the antisymmetric
situation (a Janus interface), with a hydrophilic surface on one
side to contain the water and a hydrophobic surface on the other
to force it away.

2) The authors report an experimental study of water in a Janus
interface. The main result is that when water is confined
between the two competing tendencies of a hydrophilic and
hydrophobic surface, the result is neither simple wetting nor
dewetting. The authors report that instead they observe giant
fluctuations (of the dynamical shear responses) around a
well-defined mean. This noise and fluctuation are peculiar to
water and are not observed with nonpolar fluids or with a polar
fluid such as ethanol. Aqueous films in the confined,
symmetrically hydrophilic situation also give stable dynamical
responses. The implied spatial scale of fluctuations is enormous
compared to the size of a water molecule and lends support to
the theoretical prediction that an ultrathin gas gap forms
spontaneously when an extended hydrophobic surface is immersed
in water (5).

3) The atomically smooth clay surfaces used in this study --
muscovite mica (hydrophilic) and muscovite mica blanketed with a
methyl-terminated organic self-assembled monolayer (hydrophobic)
-- allowed the surface separation to be measured by multiple
beam interferometry. Pairs of hydrophilic-hydrophobic surfaces
were brought into proximity by means of a surface forces
apparatus (3) modified for dynamic oscillatory shear. A droplet
of water was placed between the two surfaces oriented in crossed
cylinder geometry.

4) In summary: Water confined between adjoining hydrophobic and
hydrophilic surfaces (a Janus interface) is found to form stable
films of nanometer thickness whose responses to shear
deformations are extraordinarily noisy. The power spectrum of
this noise has been quantified. In addition, the frequency
dependence of the complex shear modulus is a power law with
slope one-half, indicating a distribution of relaxation
processes rather than any dominant one. The authors suggest that
the physical picture emerges that whereas surface energetics
encourage water to dewet the hydrophobic side of the interface,
the hydrophilic side constrains water to be present, resulting
in a flickering, fluctuating complex. 

References (abridged):

1. W. Kauzmann, Adv. Prot. Chem. 14, 1 (1959)

2. C. Tanford, The Hydrophobic Effect-Formation of Micelles and
Biological Membranes (Wiley-Interscience, New York, 1973). 

3. J. N. Israelachvili, Intermolecular and Surface Forces
(Academic Press, New York, ed. 2, 1991). 

4. F. H. Stillinger, J. Solution Chem. 2, 141 (1973) . 

5. E. Ruckinstein and P. Rajora, J. Colloid Interface Sci. 96,
488

Science 2002 295:663

Related Background:

ON WATER AT PROTEIN SURFACES

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

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

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

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

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

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8. ON THE HYDROPHOBIC EFFECT

R. Breslow et al (Columbia University, US) discuss the
hydrophobic effect, the authors making the following points:

1) When organic reactions are performed in water they can be
influenced by the hydrophobic effect (1), which reflects the
high energy of a water interface with a nonpolar molecule or
region. Diels-Alder reactions (2-5) and the benzoin condensation
show such effects. The hydrophobic effect itself can lead to
higher rates for these reactions in water than in other
solvents, and higher endo selectivity for Diels-Alder reactions.
It can be diagnosed by seeing the effect of added substances
that increase or decrease the hydrophobic effect; prohydrophobic
additives are generally simple salts such as sodium or lithium
chloride, while antihydrophobic additives include salts of large
ions such as guanidinium perchlorate. It has been demonstrated
that such antihydrophobic ions, which are often used as protein
denaturants, function by bridging between the nonpolar surface
and the water solvent.

2) Cosolvents such as ethanol also serve as bridging species in
water, diminishing the hydrophobic effect. This is most easily
diagnosed from the increased solubility of nonpolar substances
in such mixed solvents. Because solubility is an equilibrium
constant, its log reflects a free energy of solution, and the
increased solubility produced from an antihydrophobic additive
to water can be described in terms of a change of the free
energy of solution. This free energy change is directly
proportional to the log of the ratio of the solubilities with
and without the cosolvent.

3) Antihydrophobic agents such as organic cosolvents have been
very useful as a method of experimentally measuring the
solvation properties of transition states for reactions in
water, particularly the amount of exposed hydrophobic surface
area relative to that of the starting materials (4,5). The use
of small amounts of cosolvents allows the observation of a
change in solvation of hydrophobic surfaces while preserving the
essentially aqueous environment.

4) Grunwald (1984) has proposed two additive terms to describe
the partial molar thermodynamic properties of water-rich aqueous
alcohol solutions. The first term, called the "isodelphic" term,
describes effects on a solute where the bulk aqueous solvent
network theoretically remains unchanged upon addition of small
amounts of an alcohol cosolvent. The second term, called the
"lyodelphic" term, describes effects due to changes in the
solvent network resulting from the cosolvent.

References (abridged):

1. Tanford, C. The Hydrophobic Effect: Formation of Micelles and
Biological Membranes, 2nd ed.; John Wiley & Sons: New York, 1980.

2. Breslow, R.; Rideout, D. C. J. Am. Chem. Soc. 1980, 102, 7817.

3. Breslow, R.; Maitra, U. Tetrahedron Lett. 1984, 25, 1239-1240.

4. Breslow, R. Acc. Chem. Res. 1991, 24, 159-164.

5. Breslow, R. Hydrophobic and Antihydrophobic Effects on
Organic Reactions in Aqueous Solution; Cramer, C. J., Truhlar,
D. G., Eds.; American Chemical Society: Washington, DC, 1994; pp
291-302.

J. Am. Chem. Soc. 2002 124:3622

Related Background:

MOLECULAR VS. MACROSCOPIC HYDROPHOBIC INTERACTIONS

H.S. Ashbaug h and M.E. Paulaitis (Princeton University, US)
discuss hydrophobic interactins. The distinction between
molecular hydrophobic effects, quantified by
hydrocarbon-to-water transfer free energies, and hydrophobic
driving forces that influence self-assembly on larger length
scales (e.g., micelle formation and protein folding) was first
noted by C. Tanford in 1979. His observation was based on the
large discrepancy between the measured water-hydrocarbon
interfacial tension and the incremental free energy of
hydrophobic hydration per solute surface area obtained from
n-alkane solubility data. Israelachvili et al (1976) also noted
this discrepancy in proposing an elementary theory of surfactant
self-assembly in aqueous solution. Adopting the phenomenological
approach of linearly correlating free energies of hydrophobic
hydration with solute surface areas, they resolved the
discrepancy by defining n-alkane surface areas with respect to
the van der Waals surface, rather than with respect to the
solvent-accessible surface of these hydrocarbons. Thus, they
calculated a hydration free energy/surface area coefficient from
n-alkane solubility data that was close to the experimental
value for the macroscopic water-hydrocarbon interfacial tension.
A more recent example of the distinction between molecular and
macroscopic hydrophobic interactions is found in measurements of
a long-range attractive force between macroscopic hydrophobic
surfaces which cannot be explained on the basis of molecular
hydrophobic effects. The lack of a definitive interpretation of
these measurements underscores the need for a quantitative
theory of hydrophobic phenomena beyond molecular hydrophobic
effects. In general, the need for a unified and quantitative
description of both molecular and macroscopic hydrophobic
phenomena arises because hydrophobic driving forces play an
important role in self-assembly on intermediate length scales
and the fact that quantitative descriptions of these driving
forces are derived from molecular solubility data, macroscopic
interfacial tension measurements, or interpolation of these
quantities.

J. Am. Chem. Soc. 2001 123:10721

Related Background:

HYDROPHOBIC MOLECULAR INTERACTIONS

T.M. Raschke et al (Stanford University, US) discuss theoretical
studies of hydrophobic molecular interactions. The hydrophobic
interaction, the tendency for nonpolar molecules to aggregate in
solution, is a major driving force in biology, a force that
stabilizes biological structures ranging from native
conformations of proteins to cellular membranes, and the origin
of this effect has been the topic of much investigation, both
experimental and theoretical. In a direct approach to the
physical basis of the hydrophobic effect, the authors performed
nanosecond molecular dynamics simulations on increasing numbers
of hydrocarbon solute molecules in water-filled boxes of
different sizes. The intermittent formation of solute clusters
gives a free energy that is proportional to the loss in exposed
molecular surface area with a constant of proportionality of 45
+- 6 calories per mole per square angstrom. The molecular
surface area is the envelope of the solute cluster that is
impenetrable by solvent and is somewhat smaller than the more
traditional solvent-accessible surface area, which is the area
transcribed by the radius of a solvent molecule rolled over the
surface of the cluster. When a factor relating molecular surface
area to solvent accessible surface area is applied, the
proportionality constant is 24 calories per mole per square
angstrom. The authors suggest this is the first direct
calculation of the hydrophobic interaction from molecular
dynamics simulations, and that the excellent qualitative and
quantitative agreement with experiment demonstrates that simple
van der Waals interactions and atomic point-charge
electrostatics account for the most important driving force in
biology.

Proc. Nat. Acad. Sci. 2001 98:5965

Related Background:

SURFACE TOPOGRAPHY AND HYDROPHOBIC HYDRATION OF BIOMOLECULES

Cheng and Rossky (University of Texas Austin, US) present
computer simulations of the interactions between the polypeptide
mellitin and water. Many biomolecules are characterized by
surfaces containing extended nonpolar regions, and the
aggregation and removal of such surfaces from water is believed
to play a critical role in the biomolecular assembly in cells. A
better understanding of the hydrophobic hydration of
biomolecules may therefore yield new insights into intracellular
assembly. Conventional views hold that the hydration shell of
small hydrophobic solutes is clathrate-like, characterized by
local cage-like hydrogen-bonding structures and a distinct loss
in entropy. The hydration of extended nonpolar planar surfaces,
however, appears to involve structures that are orientationally
inverted relative to clathrate-like hydration shells, with
unsatisfied hydrogen bonds directed toward the hydrophobic
surface. The authors suggest their computer simulations
demonstrate that the two different hydration structures also
exist near a biomolecular surface, and that the two structures
are distinguished by a substantial difference in water-water
interaction enthalpy. The authors further suggest that the
strong influence of surface topography on the structure and free
energy of hydrophobic hydration is likely to hold in general,
and will be particularly important for the many biomolecules
whose surfaces contain convex patches, deep or shallow concave
grooves, and roughly planar areas.

Nature 1998 392:696

Related Background:

PRESSURE DEPENDENCE OF HYDROPHOBIC INTERACTIONS OF PROTEINS

The term "denaturation of proteins" refers to an alteration of
protein folding structure by heat, acid, alkali, mechanical
shaking, etc., the result a change in physical properties such
as solubility. "Hydrophobic aggregates" are aggregates of
nonpolar moieties, the aggregation often resulting from Van der
Waals interactions (i.e., dispersion interactions), and in the
case of many proteins, such aggregates of hydrophobic protein
side chains play an important role in producing particular
folding conformations. Clathrates are molecular compounds formed
by the inclusion of molecules of one type in holes in the
lattice of another type, and clathrate hydrates are clathrates
involving significant hydration as a component of the inclusion
compound.

Hummer et al (5 authors at 3 installations, US) report a model
explaining pressure denaturation of proteins by the pressure
destabilization of hydrophobic aggregates, the model using
information theory of hydrophobic interactions, with clathrate
hydrates predicted to form by virtually the same mechanism that
drives pressure denaturation of proteins. The authors suggest
that studies of changes in protein conformation with pressure
will not only elucidate the fundamentals of conformation
thermodynamics, but will also clarify adaptation processes of
barophilic organisms such as those living under extreme
pressures in the deep sea.

Proc. Nat. Acad. Sci. 1998 95:1552

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9. ON THE COSMOLOGICAL CONSTANT: A NEW LIMIT

In cosmology, the "cosmological constant" is a mathematical term
introduced by Einstein into the equations of general relativity,
the purpose to obtain a solution of the equations corresponding
to a "static universe". The term describes a pressure (if
positive) or a tension (if negative) which can cause the
Universe to expand or contract even in the absence of any
matter. In other words, the cosmological constant represents an
effective "vacuum energy". When the expansion of the Universe
was discovered, Einstein apparently began to regard the
introduction of this term as a mistake, and he described the
cosmological constant as the "greatest mistake of my life". But
the term has reappeared as the proposed source of apparent
accelerated cosmic expansion.

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

The term "Sachs-Wolfe effect" refers to a temperature anisotropy
expected in the cosmic microwave background due to the
gravitational effect of large-scale mass condensations. If the
potential of such a condensation is still changing, the
blueshift of a photon falling into the potential well is not
entirely canceled out by the redshift of the photon as it
emerges, leading to a net energy change.

The "Sunyaev-Zel'dovich effect" (SZ effect) is named after
Rasheed A. Sunyaev and Yakov B. Zel'dovich (1914-1987), who
first drew attention to it on theoretical grounds. This effect
is an apparent change in temperature of the microwave background
in the direction of extremely hot (100 million kelvins) ionized
gas clouds (plasma clouds) such as the plasma clouds around and
permeating rich clusters of galaxies. The effect is caused by
inverse Compton scattering of microwave background photons from
highly energetic electrons in rich-cluster plasmas. The result
of the effect, when seen with a radio telescope, is that the
number of radio-frequency photons is depleted (having moved to
higher energies), so the radio-wave radiation appears cooler.
The effect demonstrates that the photons truly originate from
behind the cluster (in the background), so the photons can be
used to determine the distance to the cluster. The value of the
Hubble constant can thus be inferred by comparison of the x-ray
luminosity of a galaxy to its microwave decrement.

"The Hubble constant" is a measure of the rate of expansion of
the Universe, the average value of velocity of recession divided
by distance. Since the constant is time-dependent, it is more
correctly termed a parameter. It's present value is believed to
be between 60 and 75 km/sec/megaparsec. One parsec equals 3.262
light-years, or 30.86 x 10^(12) kilometers.

Redshift (symbol: z) is a lengthening of the wavelengths of
electromagnetic radiation from a source caused either by the
movement of the source (Doppler effect) or by the expansion of
the universe (cosmological redshift). Redshift is defined as the
change in wavelength of a particular spectral line divided by
the unshifted wavelength of that line. Large redshifts imply
large radial velocities (which imply large distances, according
to current cosmological theory), but at redshifts greater than
about 0.2 there is a relativistic divergence from a linear
relation. A redshift of 4.0 corresponds to an object receding
with a radial velocity 92% that of the velocity of light. The
largest astrophysical redshifts so far observed are of the order
of z = 5.

A Doppler spectral change can be either a shift to the red
(redshift) or a shift to the blue (blueshift) part of the
spectrum: movement of the source toward the observer produces a
blueshift [see Note below]. Except for local galactic movements,
no cosmological blueshifts are known, and this emphasizes the
difference between Doppler redshift and cosmological redshift:
Usually, when we speak of a Doppler redshift implying a certain
recessional velocity, we mean that the shift is due to the
inherent motion of the source relative to the observer. But
regarding cosmological (galactic) redshifts in such a manner
leads to a picture of all galaxies streaming away from us, such
a picture implicitly placing our Galaxy in the center of some
great explosion, a point of view inconsistent with the
"cosmological principle", which holds that there is no center to
the Universe, that the Universe is everywhere isotropic on the
largest scales (from which it follows that the Universe is also
homogeneous). Thus, the apparent recession velocity of galaxies
is something different from the usual concept of a recession
velocity, and in fact cosmological redshift is due to the
properties of space itself, and since the shift is to the red
end of the spectrum, the implication is that space is expanding
everywhere, with every galaxy seeing every other galaxy
receding. This overall motion of galaxies away from one another
is called the "Hubble flow" after its discoverer Edwin Hubble
(1889-1953). (Note: Our own Galaxy and the nearby Andromeda
galaxy are in gravitational association, and the Andromeda
Doppler shift is in fact blue, since the Andromeda galaxy is
moving toward us.)

So-called "cold dark matter models" are now the most popular
explanation for the growth of structure in the distribution of
galaxies. The premise of these models is that most of the mass
in the Universe resides in some unseen ("dark") and relatively
massive type of particle. The particle is "cold" because it is
massive and travels slowly. The particle interacts with ordinary
matter only via the force of gravity, and could also account for
the apparent missing mass in galaxies and galaxy clusters.

In galaxies, particularly in spiral galaxies, the "missing mass
problem" concerns our inability to account for the motions of
stars at the edges of the galaxy using estimates of galactic
mass based on luminosities of the galaxy members. At the level
of clusters of galaxies, the missing mass problem is more a
question of assumptions concerning the physical basis of
nonuniform distributions of galaxies. In both cases, it is a
matter of asking what one would need to postulate in order to
explain observational data.

S.P. Bough and R.G. Crittenden (Haverford College, US) discuss
the cosmological constant, the authors making the following
points:

1) Recent observations of supernova light curves [1] suggest
that the expansion of the Universe is accelerating rather than
decelerating. Combined with evidence from the cosmic microwave
background (CMB) [2-4] and a number of other observations [5],
this suggests that the Universe is spatially flat and dominated
by a cosmological constant of approximately 0.6 to 0.7.Such a
low value of is difficult to explain from fundamental grounds,
so it is vital that we try to confirm this result by other means.

2) CMB anisotropies can arise via the integrated Sachs-WoIfe
effect (1967) as the photons travel through the time-dependent
gravitational potentials of collapsing structures. One
consequence of a large cosmological constant is that such
time-dependent potentials exist even on very large scales where
the collapse is linear, which is not the case for a flat, matter
dominated universe. These fluctuations are likely to be small
compared to those imprinted on the surface of last scattering
(redshifts z approximately 1000) and are difficult to detect
directly, however, they can be observed by looking for spatial
correlations between the CMB and the nearby matter density. This
requires a probe of the matter density out to redshifts of z ~
2, and suggested candidates include radio galaxies, quasars, and
the x-ray background.

3) Other processes can also lead to correlations between the CMB
and the local matter density. These include gravitational
lensing, scattering from hot electrons (the Sunyaev-Zeidovich
effect), and photons passing through the time-dependent
potentials of nonlinear collapsing structures (the Rees-Sciama
effect). While the study of these effects can also benefit from
cross-correlation analyses], the integrated Sachs-WoIfe effect
is unique in that it occurs on very large scales where the
fluctuations are simple and linear.

4) The authors present a new limit on the cosmological constant
based on the absence of correlations between the cosmic
microwave background (CMB) and the distribution of distant radio
sources. In cosmological constant, cold dark matter (ACDM)
models, such correlations should have been produced via the
integrated Sachs-WoIfe effect, assuming that radio sources trace
the local (z approximately 1) matter density. The authors report
they find no evidence of correlations and obtain a 95%
confidence level upper limit on the cosmological constant of
0.74. The authors suggest that if the cosmological constant lies
between 0.6 and 0.7, as suggested by recent CMB anisotropy and
supenovae observations, then the integrated Sachs-WoIfe effect
should be detectable with upcoming CMB maps and radio surveys.

References (abridged):

1. A. Riess et al., Astron. J. 116, 1009 (1998); S. Perimutter
et al., Astrophys. J. 517, 565 (1999).

2. P. de Bemardis et al.. Nature (London) 404, 955 (2000); B.
Netterfield et al., astro-ph/0104460.

3. S. Hanany et al., Astrophys. J. 545, L5 (2000); A. T. Lee et
al., astro-ph/0104459.

4. C. Pryke et al., astro-ph/0104490.

5. N. Bahcall, J. P. Ostriker, S. Perimutter, and P. J.
Steinhardt, Science 284, 1481 (1999).

Phys. Rev. Lett. 2002 88:021302

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10. ON SOLID-STATE CONVECTION OF EARTH'S LOWER MANTLE

Seismic studies indicate the interior of the Earth consists of
three parts: a metallic core, a dense rocky mantle, and a thin
low-density crust. The central part of the core is solid, but
the outer part of the core is evidently liquid. The mantle, the
layer of dense rock and metal oxides between the molten part of
the core and the surface, has plastic properties (i.e., it is a
solid capable of flow under pressure).

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. The term "subduction" refers to the
process of underthrusting of the edge of an oceanic plate into
the mantle underlying an adjacent plate.

"Mantle plumes" are thin vertical conduits of molten rock
material from the core-mantle boundary to the crust.

A.K. McNamara et al (University of Michigan, US) discuss Earth's
mantle, the authors making the following points:

1) Seismological observations reveal highly anisotropic patches
at the bottom of the Earth's lower mantle, whereas the bulk of
the mantle has been observed to be largely isotropic (1-4).
These patches have been interpreted to correspond to areas where
subduction has taken place in the past or to areas where mantle
plumes are upwelling, but the underlying cause for the
anisotropy is unknown — both shape-preferred orientation of
elastically heterogenous materials (5) and lattice-preferred
orientation of a homogeneous material have been proposed. Both
of these mechanisms imply that large-strain deformation occurs
within the anisotropic regions, but the geodynamic implications
of the mechanisms differ. Shape-preferred orientation would
imply the presence of large elastic (and hence chemical)
heterogeneity whereas lattice-preferred orientation requires
deformation at high stresses.

2) The authors report that on the basis of numerical modelling
incorporating mineral physics of elasticity and development of
lattice-preferred orientation, that slab deformation in the deep
lower mantle can account for the presence of strong anisotropy
in the circum-Pacific region. In this model — where development
of the mineral fabric (the alignment of mineral grains) is
caused solely by solid-state deformation of chemically
homogeneous mantle material — anisotropy is caused by
large-strain deformation at high stresses, due to the collision
of subducted slabs with the core–mantle boundary.

References (abridged):

1. Lay, T., Williams, Q. & Garnero, E. J. The core-mantle
boundary layer and deep Earth dynamics. Nature 392, 461-468
(1998).

2. Lay, T., Williams, Q., Garnero, E. J., Kellogg, L. &
Wysession, M. E. in The Core-Mantle Boundary (eds Gurnis, M.,
Wysession, M. E., Knittle, E. & Buffett, B. A.) 299-318
(Geodynamics Series Vol. 28, Am. Geophys. Union, Washington DC,
1998).

3. Kendall, J. M. in Earth's Deep Interior: Mineral Physics and
Tomography from the Atomic to the Global Scale (eds Karato, S.,
Forte, A. M., Liebermann, R. C., Masters, G. & Stixrude, L.)
133-159 (Geophysics Monograph 117, Am. Geophys. Union,
Washington DC, 2000).

4. Ritsema, J. Evidence for shear velocity anisotropy in the
lowermost mantle beneath the Indian Ocean. Geophys. Res. Lett.
27, 1041-1044 (2000).

5. Kendall, J. M. & Silver, P. G. Constraints from seismic
anisotropy on the nature of the lowermost mantle. Nature 381,
409-412 (1996).

Nature 2002 416:310

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11. ON AEROSOLS AND CLOUD MICROPHYSICS

The term "aerosol" refers to a dispersion in which a finely
divided solid is suspended in air and the particles are of
colloidal dimensions. The term "colloidal dimensions" refers to
the range approximately 1 nanometer to 100 nanometers in
diameter.

F-M. Breon et al (Atomic Energy Commission Gif sur Yvette, FR)
discuss aerosols, the authors making the following points:

1) Aerosols may reduce the degree of Earth global warming
resulting from the increase of greenhouse gases in the
atmosphere (1, 2). They directly impact the radiative balance of
Earth through a net increase of its albedo, particularly over
the oceans (3, 4). Aerosols can also act as cloud condensation
nuclei, increasing the number of droplets in clouds, which tends
to decrease the mean droplet size and may increase the cloud
albedo (5), depending on the aerosol absorption and cloud
optical thickness. This process, referred to as the "Twomey
effect" or the "first indirect" aerosol radiative forcing, has a
net cooling effect on climate. A direct demonstration of the
aerosol effect on cloud albedo was provided by the observation
of lines of larger reflectance in cloud fields identified as
tracks of ship exhaust. Indirect observations of this effect can
also be made by comparing cloud droplet size and aerosol
concentration. Cloud droplet effective radii were derived by
using global scale advanced very high resolution radiometer
measurements. The results of a global application indicate a
contrast in cloud droplet size of about 2 microns over land and
ocean surfaces, as well as a hemispheric contrast of 1 micron,
both of which support the Twomey hypothesis. Similar patterns of
the aerosol optical thickness and the cloud droplet effective
radius, derived from advanced very high resolution radiometer
measurements, have been observed over the oceans. Cases of
reduced droplet radii and suppression of rain -- the second
indirect aerosol effect-- in areas of high aerosol load were
identified on satellite imagery. Furthermore, several in situ
measurements have shown a relationship between the aerosol
concentration and the cloud droplet size distribution.

2) The authors report a study in which aerosol concentration and
cloud droplet radii derived from space-borne measurements are
used to explore the effect of aerosols on cloud microphysics.
Cloud droplet size is found to be largest (14 microns) over
remote tropical oceans and smallest (6 microns) over highly
polluted continental areas. Small droplets are also present in
clouds downwind of continents. By using estimates of droplet
radii coupled with aerosol load, a statistical mean relationship
is derived. The cloud droplet size appears to be better
correlated with an aerosol index that is representative of the
aerosol column number under some assumptions than with the
aerosol optical thickness. This study reveals that the effect of
aerosols on cloud microphysics is significant and occurs on a
global scale.

3) The authors conclude: Whether the observed impact on cloud
microphysics is of anthropogenic origin is a question of
importance. The satellite measurement cannot unambiguously
distinguish natural and human-generated aerosols. However, the
analysis of the spatial and temporal patterns in the aerosol
index monthly maps strongly suggests that the bulk of the
aerosol load originates from slash-and-burn agriculture
practices and from highly polluted areas (25). A large fraction
of the observed aerosol effect on clouds is probably an
anthropogenic impact.

References (abridged):

1. J. E. Penner, et al., Bull. Am. Meteorol. Soc. 75, 375 (1994)

2. R. J. Charlson, et al., Science 255, 423 (1992)

3. J. Haywood, V. Ramaswamy, B. Soden, Science 283, 1299 (1999)

4. O. Boucher and D. Tanré, Geophys Res. Lett. 27, 1103 (2000)

5. S. Twomey, J. Atmos. Sci. 34, 1149 (1977)

Science 2002 295:834

Related Background:

ANTHROPOGENIC ATMOSPHERIC AEROSOLS AND GLOBAL CLIMATE CHANGE

... Aerosols are an important component of atmospheric chemical
dynamics, with the contributions of aerosols to global and
regional climate far from simple.

... ... S.E. Schwartz and P.R. Buseck (2 installations, US)
present a commentary on recent research on anthropogenic
atmospheric aerosols, the authors making the following points:

1) Most considerations of global climate change caused by human
activities have focused on the warming influence of greenhouse
gases. However, aerosols are another important atmospheric
constituent that influences climate and that has been affected
by human activities. In general, aerosol particles increase
scattering and absorption of shortwave (solar) radiation,
increase cloud reflectance, enhance cloud lifetimes, and
suppress precipitation. These phenomena are all thought to exert
a cooling influence on climate. Recent data indicate that
anthropogenic aerosols reduce cloud droplet size and suppress
precipitation downward of major urban areas and industrial
facilities, which is consistent with earlier hypotheses.

2) The influences of aerosols on climate are more complex than
those of greenhouse gases. Bulk aerosol composition is highly
variable spatially and temporally because of different sources
and production mechanisms and short atmospheric residence times
(from less than a day to more than a month). Particles sizes
range from nanometers to microns, and within the same size
class, particles can exhibit widely different compositions and
morphologies, with different constituents present within the
same particle (e.g., 10 nanometer carbon spherules can be found
embedded within much larger sulfate particles). The
inhomogeneities in properties and geographical distribution of
aerosols make it difficult to characterize their influences on
climate and to represent these influences in models.

3) Recent analysis of the consequence of absorption of shortwave
radiation by aerosols indicates that the heating of the
atmosphere can evaporate clouds. Clouds exert both cooling and
warming influences on climate: cooling in the shortwave (because
of their reflectance), and warming in the longwave (because of
absorption and re-emission of thermal infrared radiation). The
shortwave component dominates, so a reduction in cloud coverage
would result in a net warming influence.

4) The authors conclude: "Recent studies demonstrate both the
importance of aerosol effects on climate and the complexity of
aerosol-cloud interactions. Unfortunately for those would like a
quick and accurate assessment of anthropogenic climate forcing
over the industrial period, the studies also demonstrate that
there is much to be learned before such an assessment can
confidently be given."

Science 2000 288:989

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12. ON CLUSTERED STAR FORMATION

Ralph E. Pudritz (McMaster University, CA) discusses star
formation, the author making the following points:

1) Stellar clusters are associated with every type of galaxy and
range from hundreds of stars, as is commonly observed for young
star clusters in the disk of the Milky Way (1-3), to the
millions of stars that populate the super star clusters in
prototypical starburst galaxies such as M82 (4, 5) and
interacting galaxies such as the Antennae. Stellar clusters were
also among the first systems that formed as galaxies were
assembled billions of years ago, as is evidenced by the
ubiquitous presence of globular star clusters around galaxies of
all kinds. Globular clusters are akin to super star clusters in
their mass and size but are the oldest objects yet discovered in
the Universe, ranging in age from 12 to 15 billion years, the
oldest being found in a more spherical spatial distribution in
the halos of galaxies. There is also growing evidence that the
stellar content of any star cluster, as measured by the mass
spectrum of the stars that compose it [the "initial mass
function"), is fairly robust and independent of environment.
Star clusters form at all epochs of galactic evolution, are
associated with galaxies of all Hubble types, and have similar
initial mass functions, which suggest a common and robust
mechanism of star formation.

2) Stars in the Milky Way and other nearby galaxies form in cold
[temperature (temperature 10 to 20 kelvins), self-gravitating
molecular clouds whose masses lie in the range from 10^(3) to
10^(6.5) solar masses [the Sun's mass (M) = 2 × 10^(33) grams].
Infrared observations of young embedded stars within clouds
reveal that their formation is restricted to smaller regions of
higher than average gas density called clumps. One of the
important recent advances in star formation research is the
realization that most stars form as members of star clusters
within such clumps and not in isolation from one another. Star
clusters are therefore not exotic novelties in the Universe but
are the representative products of the process of star formation.

3) In summary: Star clusters are ubiquitous in galaxies of all
types and at all stages of their evolution. They are also
observed to be forming in a wide variety of environments,
ranging from nearby giant molecular clouds to the supergiant
molecular clouds found in starburst and merging galaxies. The
typical star in our own galaxy and probably in others formed as
a member of a star cluster, so star formation is an
intrinsically clustered and not an isolated phenomenon. The
greatest challenge regarding clustered star formation is to
understand why stars have a mass spectrum that appears to be
universal.

References (abridged):

1. C. J. Clarke, I. A. Bonnell, L. A. Hillenbrand, in Protostars
and Planets IV, V. Mannings, A. P. Boss, S. S. Russell, Eds.
(Univ. of Arizona Press, Tucson, AZ, 2000), pp. 151-177.

2. B. G. Elmegreen, Y. Efremov, R. E. Pudritz, H. Zinnecker, in
Protostars and Planets IV, V. Mannings, A. P. Boss, S. S.
Russell, Eds. (Univ. of Arizona Press, Tucson, AZ, 2000), pp.
179-215.

3. C. J. Lada, in The Origins of Stars and Planetary Systems, C.
J. Lada, N. D. Kylafis, Eds. (Kluwer, Dordrecht, Netherlands,
1999).

4. R. W. O'Connell, J. S. Gallagher, D. A. Hunter, W. N. Colley,
Astrophys. J. 446, L1 (1995)

5. J. S. Gallagher and L. J. Smith, Mon. Not. R. Astron. Soc.
304, 540 (1999)

Science 2002 295:68

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13. ON TUBERCULOSIS IN NEW YORK 1990-1999

Clinical tuberculosis is a disease caused by Mycobacterium
tuberculosis, Mycobacterium bovis, or Mycobacterium africanum.
Other mycobacteria cause diseases similar to tuberculosis, but
they generally respond poorly to drugs effective for
tuberculosis.

The Mycobacteria are rod-shaped aerobic bacteria that do not
form spores. Although they do not stain readily, once stained,
they resist decoloration by acid or alcohol, and are therefore
called "acid-fast" bacilli. There are more than 50 mycobacteria
species. Mycobacterium leprae causes leprosy. In tissue,
Mycobacterium tuberculosis bacilli are thin straight rods
measuring approximately 0.4 x 3 microns. On artificial media,
both spherical and rod forms occur. True tubercle bacilli are
acid-fast, the characteristic dependent on the integrity of the
waxy envelope of the organism.

In developed countries, human tuberculosis occurs almost
exclusively from inhalation of organisms dispersed as droplet
nuclei from a person with pulmonary tuberculosis whose *sputum
smear is positive. The organism may float in the air for several
hours, thus increasing the chance of spread. Case rates vary by
country, age, race, sex, and socioeconomic status. In the US,
21,337 cases were reported in 1996. The incidence of
tuberculosis has increased markedly among persons infected with
human immunodeficiency virus (HIV), particularly among male drug
users 25 to 44 years old. Signs of what is considered a
potentially very dangerous epidemic of tuberculosis have already
appeared, with the advent of HIV infection creating the
circumstances not only for an increased incidence of
tuberculosis, but also for the development of organisms
resistant to all first-line drugs.

E. Geng et al (Columbia University, US) discuss tuberculosis,
the authors making the following points:

1) Since reaching a peak of 10.5 cases per 100,000 in 1992, the
incidence of tuberculosis in the United States has declined
sharply, to just 5.8 cases per 100,000 in 2000.(1) Molecular
epidemiologic studies in cities such as San Francisco and New
York indicated that 40 percent or more of tuberculosis cases
resulted from recent transmission rather than from the
reactivation of long-latent disease.(2,3) Measures adopted by
tuberculosis-control programs and hospitals with a high case
load of patients with tuberculosis included improved
surveillance; aggressive implementation of programs of directly
observed therapy; education of physicians, aimed largely at
increasing their index of suspicion with respect to
tuberculosis; improving infection-control policies and practices
in hospitals, jails, and prisons; and ensuring the availability
of drugs to treat those with active tuberculosis.(4)

Nearly the entire decline in the numbers of cases of
tuberculosis since 1992 is accounted for by the decline in cases
among U.S.-born persons.(1) In contrast, the number of cases in
non–U.S.-born persons has not dropped at all but, rather, has
risen slightly. More than half the cases of tuberculosis in the
United States in 2000 occurred in non–U.S.-born persons. The
predominance of non–U.S.-born persons among those with
tuberculosis is greatest where tuberculosis case rates far
exceed the national average, as in California and New York
City.(5)

The authors report a DNA fingerprinting study of tuberculosis
organisms isolated from patients with culture-positive
tuberculosis in northern Manhattan from 1990 to 1999. The goal
was to identify the strains responsible for multiple infections,
presumably through recent transmission (clusters of cases), as
well as the strains found in only one patient, presumably
representing reactivation of latent infection.

The authors conclude: Findings from northern Manhattan suggest
that among foreign-born persons, tuberculosis is largely caused
by reactivation of latent infection, whereas among U.S.-born
persons, many cases result from recent transmission. Strategies
for the control and elimination of tuberculosis among
foreign-born persons at high risk should be directed toward the
treatment of latent tuberculosis infection.

References (abridged):

1. Reported tuberculosis in the United States, 2000. Atlanta:
Centers for Disease Control and Prevention, August 2001.

2. Alland D, Kalkut GE, Moss AR, et al. Transmission of
tuberculosis in New York City: an analysis by DNA fingerprinting
and conventional epidemiologic methods. N Engl J Med
1994;330:1710-1716.

3. Small PM, Hopewell PC, Singh SP, et al. The epidemiology of
tuberculosis in San Francisco: a population-based study using
conventional and molecular methods. N Engl J Med
1994;330:1703-1709.

4. Frieden TR, Fujiwara PI, Washko RM, Hamburg MA. Tuberculosis
in New York City -- turning the tide. N Engl J Med
1995;333:229-233.

5. Talbot EA, Moore M, McCray E, Binkin NJ. Tuberculosis among
foreign-born persons in the United States, 1993-1998. J. Amer.
Med. Assoc. 2000;284:2894-2900.

New Engl. J. Med. 2002 346:1453

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14. ALZHEIMER'S DISEASE: INCIDENCE, PREVALENCE, AND ECONOMIC
IMPACT

Alzheimer's disease is now tabulated as the 12th leading cause
of death in the US, with a 1997 death-rate per 100,000
population of 8.4, which is higher than homicide and legal
intervention (7.0), AIDS (6.2), and atherosclerosis (6.2). It is
estimated that by 2025 more than 20 million people worldwide
will be afflicted with the disease. In general, Alzheimer's
disease is a degenerative brain disorder that develops in mid-
to late-adult life, the disease resulting in a progressive and
irreversible decline in memory coupled with a decline in various
other cognitive functions. In terms of general pathology, the
disease is characterized by the destruction of nerve cells and
neural connections in the cerebral cortex of the brain and by a
visible and significant loss of brain mass.

The major neuropathological change in the brain of Alzheimer's
disease patients is neuronal death, particularly in regions
related to memory and cognition. One of the major pathological
features of the disease is the abundant presence of amyloid
plaques in the brain of the affected individuals. Intracellular
bundles of paired helical filaments, composed largely of
phosphorylated tau protein, accumulate in large amounts in dying
neurons. On the neuron surfaces, insoluble aggregates of
proteinaceous debris, termed "amyloid", appear in the form of
neuritic plaques and vascular amyloid deposits. The frequency
and distribution of the neurofibrillar tangles and of the
neuritic plaques appear to correlate well with the extent of the
cognitive impairment and other characteristic symptoms of the
disease. (C. Nicolau et al Proc. Nat. Acad. Sci. 2002 99:332) 

J. L. Cummings and G. Cole (University of California Los
Angeles, US) discuss Alzheimer's disease, the authors making the
following points:

1) Alzheimer disease accounts for 60% to 70% of cases of
progressive cognitive impairment in elderly patients. The total
prevalence of Alzheimer disease in the United States is
estimated at 2.3 million (range, 1.09-4.8 million).(1) The
prevalence of Alzheimer disease doubles every 5 years after the
age of 60 increasing from a prevalence of 1% among those 60- to
64-years-old to up to 40% of those aged 85 years and older.(2)
The disease is more common among women than men by a ratio of
1.2 to 1.5.(3) The number of new cases per year is estimated at
360,000 equating to 980 new cases per day or 40 new cases every
hour. The population of patients with Alzheimer disease will
nearly quadruple in the next 50 years if the current trend
continues.(1)

2) The direct costs for the care of patients in 1991 were
calculated at US $20.6 billion and the total cost was calculated
to be $76.3 billion.(4) Most direct costs of care for patients
with Alzheimer disease are absorbed by the expense of nursing
home care, approximately $47,000 per patient per year in the
US.(5)

3) Several risk factors for AD have been identified in
epidemiologic studies in addition to age and female sex. The
most potent risk factor is the presence of the apolipoprotein
epsilon-4 (APOE epsilon-4) allele. Of its 3 forms -- epsilon-2,
-3, and -4 -- only the epsilon-4 allele increases the likelihood
of developing Alzheimer disease. The lifetime risk of Alzheimer
disease for an individual without the epsilon-4 allele is
approximately 9%; the lifetime risk of Alzheimer disease for an
individual carrying at least 1 epsilon-4 allele is 29%. While
representing a substantial risk of Alzheimer disease, the
epsilon-4 genotype is not sufficiently specific or sensitive for
the diagnosis of Alzheimer disease to allow its use as a
diagnostic test. Moreover, the epsilon-4 allele appears to
increase the risk of Alzheimer disease more in white and Asian
populations than in black and Hispanic populations. Other risk
factors implicated in a variety of studies include head injury,
low serum levels of folate and vitamin B-12, elevated plasma and
total homocysteine levels, family history of Alzheimer disease
or dementia, fewer years of formal education, lower income, and
lower occupational status. Conversely, higher levels of
education, moderate levels of daily wine consumption, and higher
levels of fish in the diet have been associated with a lower
risk for Alzheimer disease. Differences in the prevalence of
Alzheimer disease among population groups worldwide suggest as
yet undisclosed genetic or environmental effects on the
prevalence of Alzheimer disease.

References (abridged):

1. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's
disease in the United States and the public health impact of
delaying disease onset. Am J Public Health. 1998;88:1337-1342.

2. Von Strauss EM, Viitanen D, De Ronchi D, et al. Aging and the
occurrence of dementia. Arch Neurol. 1999;56:587-592.

3. Gao S, Hendrie HC, Hall KS, Hui S. The relationships between
age, sex, and the incidence of dementia and Alzheimer disease.
Arch Gen Psychiatry. 1998;55:809-815.

4. Ernst RL, Hay JW. The US economic and social costs of
Alzheimer's disease revisited. Am J Public Health.
1994;84:1261-1264.

5. Max W. The economic impact of Alzheimer's disease. Neurology.
1993;43:S6-S10.

J. Am. Med. Assoc. 2002 287:2335

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15. ON AUTOMOBILE TRAFFIC CRASHES

Leonard Evans (Sigma Xi , US) discusses automobile traffic
crashes, the author making the following points:

1) The focus on vehicle factors — factors over which they have
no control — has encouraged American drivers to regard safety as
something out of their control. The American focus on airbags is
one example of this. These were mandated by a lawyer-led safety
agency that claimed safety benefits far in excess of published
technical estimates and ignored technical information
documenting their harmful effects. Before a drug can be
prescribed in the United States, it must meet two basic
standards — efficacy and safety. Airbags were not shown to meet
either, but they were not merely offered to the public, their
installation was required. Now, the US is the only country in
the world in which it is illegal to purchase a new car without a
device that is known to increase the net harm to women (Dalmotas
et al. 1996) and to increase fatality risk in children (Glass et
al. 2000). The focus on airbags contributed to postponing
mandatory belt-wearing laws, a delay that produced thousands of
additional deaths. More fundamentally, the focus on airbags
helped mislead U.S. road users into the belief that safety would
be achieved without action on their part.

2) This focus lingers on in the futile pursuit of a safe or
smart airbag and the misplaced attention given to this pursuit.
After a crash has already commenced, there is so little time for
an airbag to inflate that it must inflate at a speed high enough
to injure anyone who happens to be in the deployment space.
Making airbags less violent will reduce the injuries they cause
but will subtract from their already modest net contribution to
safety. Effective occupant protection requires that the occupant
be restrained before the crash commences.

3) Nations with safer records than the United States have
stricter alcohol laws, which they enforce more stringently;
higher belt-wearing rates; and many driver-focused policies. As
one example of the difference in attitudes, the US has an active
market in radar detectors whose only purpose is to facilitate
illegal speeding, a device that is prohibited in other countries.

References (abridged):

1. Aldman, B. 1974. Possible effects of air bag inflation on a
standing child. Proceedings of the 18th Annual Conference of the
American Association for Automotive Medicine.

2. Dalmotas, D. ]., ]. Hurley, A. German and K. Digges. 1996.
Air bag deployment crashes in Canada. Paper 96-S10-05,15th
Enhanced Safety of Vehicles Conference, Melbourne, Australia,
13-17 May.

3. Ernst, E., E. Bruhning, K. P. Glaeser and M. Schmidt. 1991.
Compatibility problems of small and large passenger cars in head
on collisions. Paper presented to the 13th International
Technical Conference on Experimental Safety Vehicles, Paris,
4-11 November.

4. Evans, L. 1991. Traffic Safety and the Driver. New York: Van
Nostrand Reinhold.

5. Evans, L. 1993. Medical accidents: No such thing? British
Medical Journal 307:1438-1439.

American Scientist 2002 90:244

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16. HISTORY OF ANTHRAX AS A BI0LOGICAL WEAPON

Bacillus anthracis has a nearly worldwide distribution, existing
in the soil in the form of extremely resistant spores and
causing infection in humans and in farm and wild animals who
have grazed on contaminated land or ingested contaminated feed.
Under natural conditions, humans acquire anthrax infection
(usually the cutaneous form) from contact with infected animals
or contaminated animal products such as hides, wool, hair, and
ivory tusks. Rarely, gastrointestinal (or oropharyngeal) anthrax
has followed the ingestion of poorly cooked infected meat. Cases
of inhalational anthrax (also known as "woolsorters' disease")
have been linked to the large scale processing of hides and wool
in enclosed factory spaces, where aerosolized anthrax spores may
be inhaled. (M.N. Swartz: New Engl. J. Med. 2001 345:1621.)

T.V. Inglesby et al (Johns Hopkins University, US) discuss
anthrax as a biological weapon, the authors making the following
points:

1) For centuries, B anthracis has caused disease in animals and
serious illness in humans.(4) Research on anthrax as a
biological weapon began more than 80 years ago.(5) Most national
offensive bioweapons programs were terminated following
widespread ratification or signing of the Biological Weapons
Convention in the early 1970s (6); the US offensive bioweapons
program was terminated after President Nixon's 1969 and 1970
executive orders. However, some nations continued offensive
bioweapons development programs despite ratification of the
Biological Weapons Convention. In 1995, Iraq acknowledged
producing and weaponizing B anthracis to the United Nations
Special Commission.(7) The former Soviet Union is also known to
have had a large B anthracis production program as part of its
offensive bioweapons program.(8) A recent analysis reports that
there is clear evidence of or widespread assertions from
nongovernmental sources alleging the existence of offensive
biological weapons programs in at least 13 countries.(6)

2) The anthrax attacks of 2001 have heightened concern about the
feasibility of large-scale aerosol bioweapons attacks by
terrorist groups. It has been feared that independent,
well-funded groups could obtain a manufactured weapons product
or acquire the expertise and resources to produce the materials
for an attack. However, some analysts have questioned whether
"weapons grade" material such as that used in the 2001 attacks
(i.e., powders of B anthracis with characteristics such as high
spore concentration, uniform particle size, low electrostatic
charge, treated to reduce clumping) could be produced by those
not supported by the resources of a nation-state. The US
Department of Defense recently reported that 3 defense employees
with some technical skills but without expert knowledge of
bioweapons manufactured a simulant of B anthracis in less than a
month for $1 million. It is reported that Aum Shinrikyo, the
cult responsible for the 1995 release of sarin nerve gas in a
Tokyo subway station, dispersed aerosols of anthrax and botulism
throughout Tokyo at least 8 times. Forensic analysis of the B
anthracis strain used in these attacks revealed that this
isolate most closely matched the Sterne 34F2 strain, which is
used for animal vaccination programs and is not a significant
risk to humans. It is probable that the cult attacks produced no
illnesses for this and other technical reasons. Al Quaeda also
has sought to acquire bioweapons in its terrorist planning
efforts although the extent to which they have been successful
is not reported.

3) In the anthrax attacks of 2001, B anthracis spores were sent
in at least 5 letters to Florida, New York City, and Washington,
DC. Twenty-two confirmed or suspected cases resulted. All of the
identified letters were mailed from Trenton, NJ. The B anthracis
spores in all the letters were identified as the Ames strain.
The specific source (provenance) of B anthracis cultures used to
create the spore-containing powder remains unknown.

References (abridged):

4. Lew D. Bacillus anthracis. In: Mandell GL, Bennett JE, Dolin
R, eds. Principles and Practice of Infectious Disease. New York,
NY: Churchill Livingstone Inc; 1995:1885-1889.

5. Christopher G, Cieslak T, Pavlin J, Eitzen E. Biological
warfare: a historical perspective. J. Am. Med. Assoc.
1997;278:412-417.

6. Monterey Institute for International Studies chemical and
biological weapons resource page. Chemical and Biological
Weapons. Monterey, Calif: Monterey Institute for International
Studies; 2001. Available at:
http://cns.miis.edu/research/cbw/possess.htm

7. Zilinskas RA. Iraq's biological weapons. J. Am. Med. Assoc.
1997;278:418-424.

8. Alibek K, Handelman S. Biohazard: The Chilling True Story of
the Largest Covert Biological Weapons Program in the World. New
York, NY: Random House; 1999.

J. Am. Med. Assoc. 2002 287:2236

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17. HEALTH EFFECTS OF GROUND-LEVEL OZONE

Ozone is a blue gas and a blue-black solid and liquid, melting
point -193 degrees centigrade, boiling point -112 degrees
centigrade. Known pathological changes are caused by exposure to
ozone, still the principal component of photochemical air
pollution. Inflammatory injury as well as nervous system
mediated changes in lung function are observed, perhaps as the
result of the formation of free radicals. Individuals with
pre-existing respiratory diseases are especially vulnerable to
the high levels of ozone found in many urban areas. The authors
recommend that people who live in high-ozone areas should not
engage in outdoor sports or strenuous outdoor activities when
ozone warnings are in effect.

K.J. Bransford and J.A. Lai (Physicians for Social
Responsibility, US) discuss ground-level ozone, the authors
making the following points:

1) Ground-level ozone, a by-product of fossil fuel combustion,
is the major component of smog. Ozone is formed from the
reaction of nitrogen oxides and volatile organic compounds, as
from power plant emissions and automobile exhaust, in the
presence of light and heat. This reaction occurs more rapidly at
higher temperatures, explaining, in part, why smog is more
marked during the summer months. Global warming would be
expected to worsen this form of air pollution.(3)

2) Ozone has been linked to decreased pulmonary function in
healthy adults, an effect that depends on exposure concentration
and duration.(4) At low levels (0.3 ppm-0.5 ppm), ozone
irritates mucous membranes of the eyes and throat and induces
chest tightness. High-level exposure (5.0 ppm-10.0 ppm) for more
than one hour can lead to pulmonary edema and death.(5)
Long-term exposure (4 or more years in areas with summer ozone
levels of 80 ppb or more for at least 1 h daily) has been
associated with adult-onset asthma in otherwise healthy,
nonsmoking individuals.(4)

3) More generally, elevated ozone levels have been found to lead
to more frequent asthma attacks, emergency department visits,
and hospitalizations; increased use of asthma medications; and
greater morbidity and mortality in patients with pre-existing
pulmonary or cardiovascular disease.(6,7) Children are at even
greater risk because their respiratory systems are still
developing, they spend significantly more time outdoors, and
they breathe more air per pound body weight than adults. One
study found that the relative risk of asthma developing in
active children (three or more outdoor sports) living in high
ozone environments is 3.3 times greater than those who did not
play those sports.

References (abrridged):

3. Spellman F, Whiting N. Environmental Science and Technology.
Rockville, Md: Government Institutes; 1999.

4. GaliziaA, Kinney PL. Long-term residence in areas of high
ozone: associations with respiratory health in a nationwide
sample of non-smoking adults. Environ Health Perspect.
1999;107:675-679.

5. US Army Corps of Engineers. Occupational Exposure to Ozone.
HQ Environmental Division Lessons, December 16,1996.

6. US Environmental Protection Agency. Health and environmental
effects of ground-level ozone. Fact sheet: July 17, 1997.

7. Gong H Jr, Wong R, Sarma RJ, et al. Cardiovascular effects of
ozone exposure in human volunteers. Am J Respir Crit Care Med.
1998:158:538-546.

J. Am. Med. Assoc. 2002 287:2285

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18. SMOKING: YEARS OF LIFE LOST AND ECONOMIC COSTS

The alkaloid nicotine [3-(1-methyl-pyrrolidyl)pyridine] is a
tertiary amine composed of pyridine and pyrrolidine rings. The
current consensus among neuropharmacologists is that nicotine is
the psychoactive drug primarily responsible for the addictive
nature of tobacco use. Nicotine is highly selective for
so-called "nicotinic receptors" for acetylcholine in the
peripheral and central nervous systems, and activation of these
receptors is the likely source of the psychoactive effects of
the drug. The nicotinic-acetylcholine receptor is a molecularly
well-characterized receptor, and its activation evidently leads
to conformation changes in its 5 subunits that result in a
transient increase of permeability of the neuron membrane to the
sodium ion. The nicotinic- acetylcholine receptor is therefore
characterized as a neurotransmitter-gated ion channel.
Concentrations of nicotine in blood rise quickly during
cigarette smoking and peak at its completion. Nicotine is also
deposited in the lungs, spleen, liver, and brain, where
concentrations are typically twice those of measurable blood
concentrations. Nicotine readily crosses the blood-brain
barrier, leading to the release of acetylcholine,
norepinephrine, dopamine, serotonin, vasopressin, growth
hormone, cortisol, prolactin, neurophysin 1, and
adrenocorticotropic hormone, and release of these substances
causes various neuropharmacological effects. Apart from the
neuropharmacological effects of nicotine, nicotine and other
constituents in cigarette smoke elevate blood pressure, cause
tachycardia, arrhythmia, and vasoconstriction in cutaneous
tissue and skin; lower body temperature; inhibit diuresis;
increase gastrointestinal tonus; antagonize ulcer healing; and
decrease pain threshold.

The Morbidity and Mortality Weekly Report (Centers for Disease
Control and Prevention, US) discusses smoking, the report making
the following points:

1) During 1995-1999, smoking caused an annual average of 264,087
deaths among men and 178,311 deaths among women in the United
States. Among adults, most smoking-related deaths were
attributed to lung cancer (124,813), ischemic heart disease
(81,976), and chronic airways obstruction (64,735). Smoking
during pregnancy resulted in the death of 599 male and 408
female infants annually.

2) For men, the average number of annual smoking-attributable
cancer deaths during 1995-1999 decreased by approximately 1,100
(to 102,812 deaths) from 1990-1994; the number of cardiovascular
disease deaths fell by approximately 28,000 (to 90,906 deaths),
and the number of respiratory disease deaths remained stable
(53,713 deaths). For women, the average number of annual
smoking-attributable cancer deaths during 1995-1999 increased by
approximately 5,800 (to 54,664 deaths), the number of
respiratory disease deaths increased by approximately 7,300 (to
44,429 deaths), and the number of cardiovascular disease deaths
fell by approximately 5,400 (to 57,699 deaths). Compared with
1990-1994, during 1995-1999, the average number of annual
smoking-attributable deaths from perinatal conditions fell from
926 to 598 for males and from 666 to 407 for females. Adult male
and female smokers lost an average of 13.2 and 14.5 years of
life, respectively, because they smoked.

3) During 1995-1999, the average annual mortality-related
productivity losses attributable to smoking for adults were
$81.9 billion. In 1998, smoking-attributable personal
health-care medical expenditures were $75.5 billion. For each of
the approximately 46.5 million adult smokers in 1999, these
costs represent $1,760 in lost productivity and $1,623 in excess
medical expenditures. Smoking-attributable neonatal expenditures
were $366 million in 1996, or $704 per maternal smoker ($8 per
adult smoker). Maternal smoking accounted for 2.3% of total
neonatal medical expenditures in 1996. The economic costs of
smoking totaled $3,391 per smoker per year.

MMWR 2002 51:300

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19. RELAXATION MECHANISMS IN STRAINED NANOISLANDS

Quantum dots are small electrically conducting regions,
typically less than 1 micron in diameter, that contain from one
to a few thousand electrons. Because of the small volume, the
electron energies within the dot are quantized, and the behavior
of the quantum dot is intermediate between that of an atom and
that of a classical macroscopic object. Such intermediate
systems are called "mesoscopic" systems, and in the past several
years great attention has been devoted to the physics of such
systems, since they apparently can provide insights into quantum
systems in general. The electronic states in quantum dots can be
probed by transport when a small *tunnel coupling is allowed
between the dot and nearby source and drain leads.

I.A. Ovid'ko (Russian Academy of Sciences, RU) discusses
strained nanoislands, the author making the following points:

1) The strain-driven formation of spatially ordered ensembles of
nanoislands recently attracted tremendous attention motivated by
their wide applications in nanotechnologies [1-5].
Self-assembled semiconductor nanoislands (quantum dots) exhibit
unique functional properties exploited in electronic and
optoelectronic devices. From an applications viewpoint, desired
functional characteristics of quantum dots crucially depend on
their structure and geometry. In particular, the formation of
misfit dislocations in quantum dots leads to dramatic
degradation of their functional properties. In this context,
knowledge of critical geometric parameters of quantum dots, at
which the formation of misfit dislocations is energetically
favorable, is of utmost importance for applications of such
dots. In addition to the technologically motivated attention to
a theoretical description of defects in nanoislands (quantum
dots), the behavioral features of nanoislands with defects are
highly interesting for understanding the fundamentals of
nanoscale effects in solids.

2) The geometry of a freestanding nanoisland opens up several
modes of stress relaxation that are geometrically forbidden or
energetically unfavorable in continuous thin films. In
particular, lateral free surfaces of a freestanding nanoisland
are capable of playing the crucial role in strain relaxation.
Actually, in contrast to the situation with continuous thin
films, misfit dislocations can be effectively generated at nodes
of the lateral free surfaces of a nanoisland and the flat
surface of either the substrate or the wetting layer, where
crystallographic and energetic conditions of the dislocation
formation are favorable.

3) The authors suggest and and theoretically examine a new
physical mechanism for strain relaxation in nanoislands, a
mechanism associated with their specific geometry and the
geometrically dependent generation of partial misfit
dislocationss at the lateral node points.

References (abridged):

I. V. A. Shchukin and D. Bimberg, Rev. Mod. Phys. 71, 1125
(1999).

2. N.N. Ledentsov et al., Semiconductors 32, 343 (1998).

3. J.A. Floro et al., Phys. Rev. Lett. 84, 701 (2000).

4. P. Sutter and M.G. Lagally, Phys. Rev. Lett. 84, 4637 (2000).

5. A. Bourett, Surf. Sci. 432, 32 (1999).

Phys. Rev. Lett. 2002 88:146103

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20. ON IN VITRO SELECTION OF FUNCTIONAL PROTEINS

Recent advances in genomic sequencing have paved the way for the
new field of "proteomics" in which researchers can explore the
diversity, interactions, structures, and functions of every
protein found in nature. As studies of natural proteins advance,
and as we develop an understanding of the detailed functions of
individual proteins, as well as an understanding of the myriad
interactions between different proteins in the biosphere, one is
tempted to look beyond proteomics. Rather than limiting our
studies to the set of protein existing on Earth, one is tempted
to ask what structures and functions might be unobserved but
nonetheless possible. Studies that go "beyond proteomics" are
motivated by a new question: "What is possible?" Indeed, what is
possible? One way to answer this question is to construct and
characterize large libraries of proteins de novo. Such
collections can serve as a "parallel universe" in which the
newly prepared proteins can be compared to the evolutionarily
selected proteins that currently exist. (D.A. Moffet and M.H.
Hecht: Chem. Revs. 2001 101:3191)

J-M. Zhou et al (University of Tsukuba, JP) discuss in vitro
selection of proteins, the authors making the following points:

1) During the past decade, several display strategies have
provided powerful and efficient techniques for the selection and
evolution of peptides and proteins. In these techniques, the
coupling of genotype and phenotype is the single most critical
determinant in the selection of functional proteins. In such
selection systems, the specific sequence information (genotype)
of members of libraries that encode the selected protein
(phenotype) can be determined from the corresponding DNA/RNA
that was introduced into the system. The gene encoding the
selected protein can then be re-amplified for further evolution
and analysis. The strategies that have been successfully
developed are either cell-dependent, involving, for example,
display on the surface of phage (1), other viruses (2), bacteria
(3) or yeast (4), or they are cell-free, as in the case of
ribosome display (5) and mRNA display systems.

2) The methods that have been developed to date are, however,
associated with certain limitations and disadvantages. Since
cell-dependent display systems (1-4) include a necessary in vivo
step, the sizes and diversity of sequence libraries are limited
by the efficiency of transformation and by the nature of the
protein in question. For example, some proteins that are
detrimental to cells or that have important regulatory functions
within cells cannot be selected. An alternative method, namely,
cell-free ribosome display (5), must be adopted at a low
temperature under conditions that preserve the integrity of the
protein-ribosome-mRNA ternary complex, with removal of a
termination codon and the addition of magnesium acetate and
anti-ssrA oligonucleotides. Moreover, the yield of the isolated
mRNAs after one round of ribosome display is not very high. In
fact, it can be as low as 0.015% of the input RNA, with a
resultant potential reduction in the diversity of the sequence
libraries. The alternative cell-free, mRNA display procedure
requires careful chemical synthesis and critical purification of
puromycin-attached oligonucleotides, which must be ligated to
the 3' end of each mRNA in the sequence libraries. Failure to
perform these manipulations appropriately leads to a reduction
in the diversity of available libraries.

3) The authors report a novel strategy for connection of
phenotype and genotype in vitro that can be used for the
selection of functional proteins even at room temperature. The
strategy involves generation of a stable complex between a
ribosome, an mRNA, and its translated protein, without removal
of the termination codon, as a result of the action of the ricin
A chain during translation. The authors demonstrate the
potential selection capacity of this novel strategy by isolating
such complexes that contain newly synthesized streptavidin and
glutathione-S-transferase (GST) using appropriate ligands. The
technique requires no transfection, no chemical synthesis, no
ligation, and no removal of the termination codon.

References (abridged):

1. Winter, G.; Griffiths, A. D.; Hawkins, R. E.; Hoogenboom, H.
R. Annu. Rev. Immunol. 1994, 12, 433-455.

2. Kasahara, N.; Dozy, A. M.; Kan, Y. M. Science 1994, 266,
1373-1376.

3. Georgiou, G.; xxPoetschke, H. L.; Stathopoulos, C; Francisco,
J. A. Trends Biotechnot. 1993, 11, 6-10.

4. Kieke, M. C.; Cho, B. K.; Boder, E. T.; Kranz, D. M.;
Wittrup, K. D. Protein Eng. 1997, 10, 1303-1310.

5. Mattheakis, L. C.; Bhatt, R. R.; Dower, W. J. Proc. Null.
Acad. Sci. U.S.A. 1994, 97, 9022-9026.

J. Am. Chem. Soc. 2002 124:538

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21. ON SILICON-BASED QUANTUM COMPUTER ARCHITECTURE

The indivisible unit of classical information is the "bit",
which takes one of two possible values, 0 or 1. Any amount of
classical information can be expressed as a sequence of bits. A
classical computer executes a series of simple operations
("gates"), each of which acts upon a single bit or pair of bits.
By executing many gates in succession, the computer can evaluate
any *Boolean function of a set of input bits. Quantum
information can also be reduced to elementary units, called
quantum bits or "qubits". A qubit is a two-level quantum system
(e.g., the spin of an electron). A quantum computer executes a
series of elementary quantum gates, each of which is a *unitary
transformation that acts on a single qubit or pair of qubits. By
executing many such gates in succession, the quantum computer
can apply a complicated unitary transformation to a particular
initial state of a set of qubits. Finally, the qubits can be
measured, the measurement outcome the final result of a quantum
computation. (J. Preskill: Physics Today 1999 June).

*unitary transformation: In this context, the term "unitary
transformation" refers to a linear operator whose adjoint is
equal to its inverse. The "adjoint" A* of an operator A is an
operator such that for all f and g in the domain of A: (Af,g) =
(f,A*g). If A* = A, then A is said to be self-adjoint.

B. Koiller et al (University of Maryland, US) discuss quantum
computers, the authors making the following points:

1) Following the proposal by Kane (1), there has been much
effort [2-4] to develop a silicon-based quantum computer
architecture. The basic ideas of the Kane proposal are simple
and attractive: to use donor nuclear spins as quantum bits
(qubits), and to utilize the vast infrastructure and technology
associated with the Si industry to fabricate precisely
controlled Si nanostructures, where exchange effects between
electrons and nuclei in neighboring donor impurities (e.g., P-31
in Si) could serve as the two-qubit gates, similar to the
electron-spin-based QC proposal by Loss and DiVincenzo [5]. The
motivation for a Si quantum computer is obvious: Once the basic
one-qubit and two-qubit operations have been demonstrated using
donor impurities in Si nanostructures, computer chip fabrication
technology associated with the existing and dominant Si industry
will easily enable the scale-up of information processing
involving a large number of donor nuclear spin qubits. Indeed,
one of the formidable stumbling blocks in developing working
quantum computer hardware has been the scale-up problem, as the
demonstrated qubits in trapped ion and liquid state NMR
techniques are not readily scalable in any significant manner.

2) A great deal of experimental work is currently aimed at
developing suitable qubits in Si nanostructures with precisely
introduced dopant impurities, using both a "top-down" approach
with ion implantation, and a "bottom-up" approach with molecular
beam epitaxy growth and scanning tunneling microscopy [4]. In
the Si quantum computer model [1,2], donor electrons act as
shuttles between different nuclear spins. For two-qubit
operations, which are required for a universal quantum computer,
both electron-electron exchange and electron-nucleus hyperfine
interaction need to be precisely controlled. These are
unquestionably formidable experimental problems. In the original
proposal, Kane used the Herring-Flicker exchange formula for two
hydrogenic centers to obtain an order of magnitude estimate of
the electron exchange among donors in Si [1]. However, as he
also pointed out, donor exchange in Si is not hydrogenic.

3) The authors report a calculation of the donor electron
exchange in silicon and germanium, and demonstrate an
atomic-scale challenge for quantum computing in Si (and Ge), as
the six (four) conduction-band minima in Si (Ge) lead to
intervalley electronic interference, generating strong
oscillations in the exchange splitting of two-donor two-electron
states. Donor positioning with atomic-scale precision within the
unit cell thus becomes a decisive factor in determining the
strength of the exchange coupling — a fundamental ingredient for
two-qubit operations in a silicon-based quantum computer.

References (abridged):

I. B.E. Kane, Nature (London) 393, 133 (1998).

2. B. E. Kane, Fortschr. Phys. 48, 1023 (2000).

3. R. Vrijen et al., Phys. Rev. A 62, 012306 (2000).

4. J.L. O'Brien et al.. Phys. Rev. B 64, 161401 (2001).

5. D. Loss and D. P. DiVincenzo, Phys. Rev. A 57, 120 (1998).

Phys. Rev. Lett. 2002 88:027903

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22. ON WATER-SOLUBLE BLOCK COPOLYMERS

A simple linear polymer is a chain molecule composed of monomers
with two reactive sites (bifunctional monomers), with
monofunctional terminal units. If more than one bifunctional
monomer is present, the chain is known as a "copolymer". A
copolymer in which a number of units of the same monomer are
located adjacent to one another (in "blocks" of monomers) is
called a "block copolymer".

Michel Arotcarena et al (Catholic University of Louvain, BE)
discuss block copolymers, the authors making the following
points:

1) Two different types of water-soluble block copolymers are
typically distinguished, namely amphiphilic block copolymers and
double-hydrophilic block copolymers. Amphiphilic block
copolymers are typically composed of a hydrophobic,
water-insoluble block that associates in aqueous solution and of
a hydrophilic block that prevents the aggregates from
precipitation (1). Due to the similarity of such aggregates to
micelles made from low molar mass surfactants (2-5), amphiphilic
block copolymers are often referred to as "macrosurfactants".
Such macrosurfactants are, for example, discussed in connection
with enzyme encapsulation or in connection with the transport
and targeting of drugs.

2) The particular structure of double-hydrophilic block
copolymers, i.e., of copolymers combining two different
hydrophilic blocks, enables one of the blocks to undergo
physical or chemical transformations in aqueous solution which
render them insoluble, while the copolymer stays in solution by
virtue of the hydrophilicity of the other block. In other
possible uses, such polymers are considered in ion sequestering
in water or in the transfection of cells.

3) An interesting combination of the two types of block
copolymers described above is double-hydrophilic block
copolymers in which one of the hydrophilic blocks is
thermoresponsive, i.e., undergoes a transition from soluble to
insoluble in water. Typically, most reports on such systems
exploit the wide-spread occurrence of a lower critical solution
temperature of nonionic polymers in water. When passing above
the critical temperature, one of the hydrophilic blocks
collapses, thus creating hydrophobic microdomains in analogy to
macrosurfactants. Or, applying the thermal stimulus in the other
direction, the aggregates formed by such block copolymers are
dissociated by lowering the temperature below a critical value.
This strategy can be used to trigger the release of encapsulated
materials, e.g. for controlled drug delivery. Alternatively,
though rarely done, the existence of an upper critical solution
temperature can also be exploited for thermoresponsive behavior.
Unfortunately, the synthesis of block copolymers containing
hydrophilic blocks is inherently difficult, because hydrophilic
monomer units typically contain electrophilic and/or
nucleophilic fragments that interfere with most living
polymerization methods. Therefore, amphiphilic block copolymers
are more frequently encountered than double-hydrophilic ones.

References (abridged):

1. Riess, G.; Hurtrez, G.; Bahadur, P. In Encyclopedia of
Polymer Science and Engineering: Mark, H. F., Bikales, N. M.,
Overberger, C. G., Menges, G.. Eds.; Wiley: New York, 1985; Vol.
2, pp 324-434.

2. Cornelissen, J. J. L. M.; Fischer. M.; Sommerdijk, N. A. J.
M.; Noltc, R. J. M. Science 1998, 280, 1427-1430.

3. Hentze, H. P.; Kramer. E.; Bcrton, B.; Forster, S.;
Antonietti, M.; Dreja. M. Macromolecules 1999, 32, 5803-5809.

4. Schuch. H.; Klingler, J.; Rossmanith, P.: Frechen, T.; Gerst,
M.: Feldhusen, J.; Miiller, A. H. E. Macromolecules 2000, 33,
1734-1740.

5. Forster, S. Ker. Bunsen-Ges. Phvs. Chem. 1997, 101, 1671-1678.

J. Am. Chem. Soc. 2002 124:3787

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23. ON CONJUGATED POLYMER INTERFACES

M.C. Lonergan et al (University of Oregon, US) discuss
conjugated polymers, the authors making the following points:

1) Central to conventional silicon microelectronics are
interfaces between regions of silicon with different doping
types (n vs p) or densities (1). Analogous interfaces based on
conjugated polymers are of interest as components of electronic
devices based on organic materials. For instance, the
performance of organic light-emitting diodes utilizing a
nominally undoped conjugated polymer can be improved by the
incorporation of a doped polymer electrode (2) and photovoltaics
based on doped | undoped polymer interfaces have been recently
reported (3).

2) Although thermodynamically unstable, interfaces between
dissimilarly doped regions of silicon are kinetically stable due
to the immobility of the dopant atoms. In contrast, the dopant
ions of conventionally doped conjugated polymers can be mobile.
The mobility of dopant ions in conventional conjugated polymers
presents a potential problem in the fabrication of interfaces
between dissimilarly doped conjugated polymers. Bulk chemical
reactions between conjugated polymers of different doping types
or densities can occur as the result of the mobility of dopant
atoms in conjugated polymers (4). The rate of such a reaction
depends on ion diffusion coefficients, which in turn depends on
the ion, polymer structure, and any incorporated solvent or
other additive. A simple illustration of the reactivity between
regions of conjugated polymers with different doping types is
the transient stability of the p-type \ intrinsic | n-type
(p-i-n) structure formed during the operation of electrochemical
light-emitting diodes (5).

3) In principle, bulk chemical reactions between dissimilarly
doped conjugated polymers can be prevented either on a
thermodynamic or a kinetic basis. An example of thermodynamic
control comes from bilayer structures such as that between
polypyrrole and poly(3-octylthiophene). Here the separation in
reduction potential for p-doping these polymers allows for
polypyrrole to be selectively oxidized in the bilayer while
leaving polythiophene undoped. In relation to electronic
devices, such interfaces would correspond to heterojunctions
based on different inorganic semiconductors. "Homojunctions"
based on a single polymer backbone would not be possible with
such an approach, nor would interfaces between n- and p-type
materials, which are generally expected to be unstable on a
thermodynamic basis.

4) Kinetic control over interfacial reactivity can be achieved
by controlling ion diffusion. A straightforward way this can be
achieved is through the use of internally compensated conjugated
polymers in which the dopant ions balancing the charge injected
into the polymer backbone are covalently bound to the polymer
and hence exhibit very low diffusion coefficients.4 The
long-term stability of interfaces based on such internally
compensated polymers is ultimately limited by the time scale for
polymer, and hence counterion, diffusion. Such kinetic stability
is analogous to that for silicon homojunctions where the
diffusion coefficients for dopant atoms sets the relevant time
scale. Restricting the mobility of dopant ions in conjugated
polymers is also essential in controlling the spatial
distribution of charges under applied bias.

References (abridged):

1. Sze, S. M. Physics of Semiconductor Devices; Wiley: New York,
1981.

2. Gross, M.; Muller, D. C.; Nothofer, H.-G.; Scherf, U.; Neher,
D.; Brauchle, C.; Meerholz, K. Nature 2000, 405, 661-665.

3. Arias, A. C.; Granstrom, M.; Thomas, D. S.; Petritsch, K.;
Friend, R. H. Phys. Rev. B 1999, 60, 1854-1860.

4. Zhou, Z.; Langsdorf, B. L.; Lonergan, M. C. Mater. Res. Soc.
Symp. Proc. 2000, 59S, BB5.7/1-BB5.7/6 (Electrical, Optical, and
Magnetic Properties of Organic Solid-State Materials V).

5. Pei, Q.; Yu, G.; Zhang, C.; Yang, Y.; Heeger, A. J. Science
1995, 269,1086.

J. Am. Chem. Soc. 2002 124:690

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24. QUANTUM CRYPTOGRAPHY: ON PRIVATE QUANTUM ENTANGLEMENT OVER
ARBITRARY DISTANCES

Quantum mechanical entanglement is a phenomenon that has caught
the imagination of the public as one of the more bizarre
consequences of fundamental physical theory. Entanglement is
unique to quantum mechanics, and involves a relationship (a
"superposition of states") between the possible quantum states
of two entities such that when the possible states of one entity
collapse to a single state as a result of suddenly imposed
boundary conditions, a similar and related collapse occurs in
the possible states of the entangled entity no matter where or
how far away the entangled entity is located. Entanglement
arises from the wave function equation of quantum mechanics,
which has an array of possible function solutions rather than a
single function solution, with each possible solution describing
a set of possible probabilistic quantum states of the physical
system under consideration. Upon fixation of the appropriate
boundary conditions, the array of possible solutions collapses
into a single solution. For many quantum mechanical physical
systems, the fixation of boundary conditions is a theoretical
and fundamental consequence of some interaction of the physical
system with something outside that system, e.g., an interaction
with the measuring device of an observer. In this context, two
entities that are described by the same array of possible
solutions to the wave function equation are said to be
"coherent", and when events decouple these entities, the
consequence is said to be "decoherence". As a physical
phenomenon, entanglement was discussed many years ago, most
particularly following the publication in 1935 of the often
quoted Einstein-Podolsky-Rosen paper (the "EPR paper") (Phys.
Rev. 1935 47:777). These discussions have been in the form of
"gedanken" (thought) experiments involving two
quantum-mechanical entangled entities. More recently, however,
there have been laboratory constructions of actual quantum
mechanical systems exhibiting such entanglement phenomena, and
the reportage of these laboratory arrangements by the media have
engaged the public fancy. Essential here is that any purely
verbal account of quantum mechanical phenomena is severely
limited by the constraint that the properties of quantum
mechanical systems can be precisely described only by the
equations relevant for those systems, and all other descriptions
usually introduce serious ambiguities. In any case, an "EPR
pair" is a pair of entangled quantum entities.

H. Aschauer and H.J. Briegel (Ludwig-Maximilians University, DE)
discuss private quantum entanglement, the authors making the
following points:

1) Quantum cryptography promises the security of data
transmission against any eavesdropping attack allowed by the
laws of physics. The first quantum cryptography protocol was
described by Bennett and Brassard as early as 1984 [1]. Later,
in 1991, Ekert presented a scheme based on Bell's theorem [2].
Though the security of these protocols is easy to prove under
ideal conditions, much work has been spent to prove the security
under realistic circumstances.

2) In all quantum cryptography protocols, a possible
eavesdropper is identified because of the disturbance that he or
she introduces when trying to gain information about a quantum
state that is transmitted. The problem is that every quantum
channel introduces innocuous noise itself, which cannot, in
principle, be distinguished from noise introduced by an
eavesdropper. For that reason, a proof of unconditional security
of quantum cryptography has to assume that all noise in the
channel is due to the interference of an eavesdropper.

3) Two different techniques have been developed to deal with
these difficulties: Classical privacy amplification allows the
eavesdropper to have partial knowledge about the raw key built
up between the communicating parties Alice and Bob. From the raw
key, a shorter key is "distilled", about which Eve has vanishing
(i.e., exponentially small in some chosen security parameter)
knowledge. Despite the simple idea, proofs taking into account
all eavesdropping attacks allowed by the laws of quantum
mechanics have been shown to be technically involved [3-5].
Recently, Shor and Preskill [2000] have given a simpler physical
proof relating the ideas in [3,4] to quantum error correcting
codes. Quantum privacy amplification, on the other hand, employs
an entanglement purification protocol that eliminates any
entanglement with an eavesdropper by creating a few perfect EPR
pairs out of many imperfect (or impure) EPR pairs. In principle,
this method guarantees security against any eavesdropping
attack. However, the problem is that the quantum privacy
amplification protocol assumes ideal quantum operations. In
reality, these operations are themselves subject to noise.

4) The authors report a security proof of quantum cryptography
based entirely on entanglement purification. Their proof applies
to all possible attacks (individual and coherent), and implies
the security of cryptographic keys distributed with the help of
entanglement-based quantum repeaters. The authors prove the
security of the obtained quantum channel, which may be used not
only for quantum key distribution, but also for secure, albeit
noisy, transmission of quantum information.

References (abridged):

1. C. H. Bennett and G. Brassard, in Proceedings of IEEE
International Conference on Computers, Systems and Signal
Processing, Bangalore, India (IEEE, New York, 1985), pp. 175-179.

2. A. Ekert, Phys. Rev. Lett. 67, 661 (1991).

3. D. Mayors, in Advances in Cryptology-Proceedings of Crypto
'96 (Springer-Verlag, New York, 1996), pp. 343-357; see also
quant-ph/9802025.

4. E. Biham et al., in Proceedings of the Thirty-Second Annual
ACM Symposium on Theory of Computing (ACM Press, New York,
2000), pp. 715-724.

5. H. Inamori, quant-ph/0008064.

Phys. Rev. Lett. 2002 88:147902

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25. IN FOCUS: ON THE STRONG AND WEAK FORCES

"The nineteenth century was a blissful childhood for science,
when Nature seemed to need only gravity and electromagnetism to
account for practically everything that cluttered the physical
world. Then, during the twentieth century, physicists uncovered
two additional natural forces operating alongside gravity and
electromagnetism. These were not at all the kinds of forces you
could ever recognize through a casual inspection of human-scale
natural events. Yet with- out them, the world would not exist,
rainbows would not grace the sky, and stars would not shine in
the heavens. Deep within the uranium atom, 92 protons and 146
neutrons jostle each other in a frantic nuclear dance. The space
is very cramped, barely one-hundred-trillionth of an inch
across. Traveling at nearly one-third the speed of light, the
particles go nowhere fast. Thanks to our grade-school teachers,
we know that positive charges repel each other, so how in the
world could 92 positively charged protons hang together in such
a cramped space without blasting the nucleus to smithereens?
There must be a force buried within the atom that overw