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SCIENCEWEEK

ScienceWeek - September 13, 2002 Vol. 6 Number 37

An Online Research Digest Published Weekly Since 1997

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Should we force science down the throats of those who have no
taste for it? Is it our duty to drag them kicking and screaming
into the 21st century? I am afraid that it is.
-- George Porter

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Section 1

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1. On Early Land Vertebrates

2. On RNA Export

3. Chromosome Conformation and Loci Interactions

4. Mars: The Crustal Dichotomy

5. On Electronic Excitations

6. Electrical Measurement and the Quantum-Classical Transition

7. On Mail-Borne Transmission of Anthrax

8. On Preeclampsia

9. An Evaluation of Radical Breast Cancer Surgery

10. On Catalytic Converters and Automotive Emission Control

11. On Photoluminescence Properties of Nanocrystals

12. On Grain Boundaries in High-Temperature Superconductors

13. ScienceWeek Notices and Subscription Information

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Section 2

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1. ON EARLY LAND VERTEBRATES

Robert Carroll (McGill University, CA) discusses early land
vertebrates, the author making the following points:

1) The transition between fish and land vertebrates was a
turning point in the history of life. Early stages in the
evolution from aquatic lobe-finned fish to tetrapods -- animals
with limbs capable of locomotion on land -- are seen in many
fossils from the Upper Devonian(1), just before 363 million
years ago. In contrast, few remains are known from the next 30
million years, when the ancestors of the major tetrapod lineages
differentiated from one another, an interval that falls in the
early part of the Carboniferous period. So striking is the
hiatus that Coates and Clack(2) coined the term "Romer's Gap"
for it, in reference to the long search of Alfred Sherwood Romer
(1894-1973) for fossils dating to that time. It is fitting that
Clack (3) should be the first to recognize a well-preserved
specimen of a new amphibian species from Romer's Gap. The
fossil, Pederpes finneyae, comes from 350-million-year-old
deposits at Dumbarton, Scotland.

2) Although the full length of the tail of Pederpes is not
known, the animal was probably nearly a meter in length. It was
a short-limbed, large-skulled predator, resembling an especially
ungainly crocodile. But it almost certainly reproduced in the
water, somewhat like modern aquatic salamanders. Grooves in the
skull for lateral-line canals — a characteristic of fish —
suggest that it lived partly in the water. The foot structure,
however, indicates it could walk on land. Pederpes is advanced
over its Devonian antecedents in having only five toes on the
foot, yet has a relict of a tiny finger on the forelimb
reminiscent of the supernumerary digits of the best-known
amphibians -- Ichthyostega and Acanthostega -- from the Upper
Devonian.

3) Discovery of a nearly complete skeleton in the middle of
Romer's Gap should help in establishing the pattern of
evolutionary change among early tetrapods. It might also provide
context for understanding the interrelationships of all later
land vertebrates. Clack demonstrates that Pederpes and other
members of the Whatcheeriidae -- the family to which it is
assigned -- occupied an intermediate grade between the primarily
aquatic Upper Devonian amphibians and later tetrapods. In
particular, the feet show major advances towards effective
locomotion on land. On the other hand, whatcheeriids have no
skeletal features that indicate specific affinities to either of
the major groups of "conservative" amphibians, the temnospondyls
or anthracosaurs, that dominated the later Carboniferous.(4,5)

References (abridged):

1. Clack, J. A. in Amphibian Biology (eds Heatwole, H. &
Carroll, R. L.) 979-1029 (Surrey Beatty, Chipping Norton,
Australia, 2000)

2. Coates, M. I. & Clack, J. A. in Studies on Early Vertebrates
(eds Arsenault, M., Lelièvre, H. & Janvier, P.) 373-388
(Bulletin du Muséum National d'Histoire Naturelle, Paris, 1995)

3. Clack, J. A. Nature 418, 72-76 (2002)

4. Carroll, R. L. in Amphibian Biology (eds Heatwole, H. &
Carroll, R. L.) 1198-1269 (Surrey Beatty, Chipping Norton,
Australia, 2000)

5. Anderson, J. S. Systematic Biol. 50, 170-193 (2001)

Nature 2002 418:35

Web Links: Romer's gap          tetrapods

Related Background Brief:

AN EARLY TETRAPOD FROM "ROMER'S GAP". The fossil record of early
tetrapods has been increased recently by new finds from the
Devonian period and mid–late Early Carboniferous period. Despite
this, understanding of tetrapod evolution has been hampered by a
20-million-year gap ("Romer's Gap") that covers the crucial
early period when many key features of terrestrial tetrapods
were acquired. The author describes the only articulated
skeleton of a tetrapod, Pederpes, yet found from the Tournaisian
epoch (354–344 million years ago (Myr)). The new taxon includes
a pes with five robust digits, but a very small, possibly
supernumerary digit preserved on the manus suggests the presence
of polydactyly. Polydactylous early tetrapods may have survived
beyond the end of the Devonian and pentadactyly cannot be
assumed for the pes. However, the pes has characteristics that
distinguish it from the paddle-like feet of the Devonian forms
and resembles the feet of later, more terrestrially adapted
Carboniferous forms. Pederpes is the earliest-known tetrapod to
show the beginnings of terrestrial locomotion and was at least
functionally pentadactyl. With its later American sister-genus,
Whatcheeria, it represents the next most primitive tetrapod
clade after those of the Late Devonian, bridging the temporal,
morphological and phylogenetic gaps that have hitherto separated
Late Devonian and mid-Carboniferous tetrapod faunas. J.A. Clack:
Nature 2002 418:72.

Related Background Brief:

THE PHYLOGENETIC TRUNK: MAXIMAL INCLUSION OF TAXA WITH MISSING
DATA IN AN ANALYSIS OF THE LEPOSPONDYLI (VERTEBRATA, TETRAPODA).
The importance of fossils to phylogenetic reconstruction is well
established. However, analyses of fossil data sets are
confounded by problems related to the less complete nature of
the specimens. Taxa that are incompletely known are problematic
because of the uncertainty of their placement within a tree,
leading to a proliferation of most-parsimonious solutions and
"wild card" behavior. Problematic taxa are commonly deleted
based on a priori criteria of completeness. Paradoxically, a
taxon's problematic behavior is tree dependent, and levels of
completeness are not directly associated with problematic
behavior. Exclusion of taxa on the basis of completeness
eliminates real character conflict and, by not allowing
incomplete taxa to determine tree topology, diminishes the
phylogenetic hypothesis. The author proposes that the
phylogenetic trunk allows optimization of taxonomic inclusion
and tree stability. The use of this method in an analysis of the
Paleozoic Lepospondyli finds a single most-parsimonious tree, or
trunk, after the removal of one taxon identified as being
problematic. Moreover, the 38 trees found at one additional step
from this primary trunk were reduced to 2 by removal of one
additional taxon. These trunks are compared with the trees that
were found by excluding taxa with various degrees of
completeness, and the effects of incomplete taxa are explored
with regard to use of the trunk. Correlated characters
associated with limblessness are discussed regarding the
assumption of character independence; however, inclusion of
intermediate taxa is found to be the single best method for
breaking down long branches. J.S. Anderson: Systematic Biology
2001 50:170.

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2. ON RNA EXPORT

Katherine S. Ullman (University of Utah, US) discusses RNA
export, the author making the following points:

1) In eukaryotic organisms, genomic DNA is housed within the
nucleus, a compartment specialized to protect genomic content,
ensure accurate DNA replication and facilitate fine-tuned gene
regulation. Production of RNA within the nucleus necessitates a
transport event in which RNAs transit through the nuclear pore
complex and on to their destinations. Mattaj and colleagues [1] 
have recently reported results that advance our understanding of
how the vast array of mRNAs are recognized as targets for
export. Their work defines a minimal stretch of unstructured RNA
as an important determinant for mRNA export and further
underscores the intimate connection between these recognition
events, the export pathway and the RNA's downstream fate.

2) Although small nuclear (sn), messenger (m), transfer (t) and
ribosomal (r) RNAs converge at the nuclear pore complex during
nucleocytoplasmic transport, different classes of RNA have
distinct requirements for export. This was first appreciated
when cross-competition analysis of RNA export revealed that the
limiting factors are not the same for each type of RNA: one
class of RNA can saturate its own route of export, while leaving
that of other RNA classes unperturbed [2,3]. Progress in the
field has since led to a molecular understanding of some of the
differences in export paths; in many cases these involve
specialized soluble factors which recognize and transport
specific RNA cargo. For instance, Exportin-t recognizes shared
features of tRNAs [4,5], whereas a cap-binding complex, along
with the adaptor PHAX, bridges U snRNAs to the export receptor
Crm1/Exportin 1.

3) The case of mRNA is unique in that we know several important
players in the mRNA export machinery, but we are just beginning
to understand how these factors recognize and load onto mature
mRNA to facilitate its export. The challenge, for the researcher
as well as the cell, lies in the diversity of mRNA.
Surprisingly, structural features known to be shared by most
mRNAs -- such as a methylated cap structure at the 5' end and
the poly(A) tail at the 3' end -- are not critical determinants
of export [2]. Many mRNAs also share a common step in their
biogenesis and that is the process of splicing. Notably,
splicing has been shown to lead to deposition onto the RNA
product of a complex of proteins, including a protein implicated
in the process of mRNA export, REF/Aly.

References (abridged):

1. Ohno M., Segref A., Kuersten S. and Mattaj I.W. (2002)
Identity elements used in export of mRNAs. Mol. Cell, 9:659-671

2. Jarmolowski A., Boelens W.C., Izaurralde E. and Mattaj I.W.
(1994) Nuclear export of different classes of RNA is mediated by
specific factors. J. Cell Biol., 124:627-635

3. Pokrywka N.J. and Goldfarb D.S. (1995) Nuclear export
pathways of tRNA and 40 S ribosomes include both common and
specific intermediates. J. Biol. Chem., 270:3619-3624

4. Arts G.J., Kuersten S., Romby P., Ehresmann B. and Mattaj
I.W. (1998) The role of exportin-t in selective nuclear export
of mature tRNAs. EMBO J., 17:7430-7441

5. Kutay U., Lipowsky G., Izaurralde E., Bischoff F.R.,
Schwarzmaier P., Hartmann E. and Gorlich D. (1998)
Identification of a tRNA-specific nuclear export receptor. Mol.
Cell, 1:359-369

Current Biology 2002 12:R461

Web Links:  mRNA mRNA transport

Related Background Brief:

NUCLEAR EXPORT OF DIFFERENT CLASSES OF RNA IS MEDIATED BY
SPECIFIC FACTORS. Various classes of RNA are exported from the
nucleus to the cytoplasm, including transcripts of RNA
polymerase I (large ribosomal RNAs), II (U-rich small nuclear
RNAs [U snRNAs], mRNAs), and III (tRNAs, 5S RNA). The authors
present evidence that some steps in the export of various
classes of nuclear RNA are mediated by specific rather than
common factors. Using microinjection into Xenopus oocytes, the
authors demonstrate that a tRNA, a U snRNA, and an mRNA
competitively inhibit their own export at concentrations at
which they have no effect on the export of heterologous RNAs.
While the export of both U snRNAs and mRNAs is enhanced by their
7-methyl guanosine cap structures, factors recognizing this
structure are found to be limiting in concentration only in the
case of U snRNAs. In addition to the specific factors, evidence
for steps in the export process that may be common to at least
some classes of RNA are provided by experiments in which
synthetic homopolymeric RNAs are used as inhibitors. A.
Jarmolowski et al: J Cell Biol 1994 124:627.

Related Background Brief:

NUCLEAR EXPORT PATHWAYS OF TRNA AND 40 S RIBOSOMES INCLUDE BOTH
COMMON AND SPECIFIC INTERMEDIATES. The transport of proteins and
RNAs in both directions across the nuclear envelope constitutes
a set of processes called "nucleocytoplasmic trafficking". Both
the import of proteins and the export of RNAs occur via the
nuclear pore complex. However, the steps responsible for the
delivery of substrates to the pore complex, variously referred
to as "targeting" and "docking", differ for protein import and
RNA export. Different classes of RNAs are exported from Xenopus
laevis oocyte nuclei by facilitated pathways. The authors report
they have performed kinetic competition analyses to investigate
the relationship between the export pathways of microinjected
tRNA and ribosomal subunits. Saturating concentrations of
ribosomal subunits do not compete with tRNA export. Thus, the
saturable factor in the ribosomal subunit export pathway is not
limiting for tRNA export. The co-microinjection of ribosomal
subunits did, however, stimulate the rate of tRNA export.
Co-injected mRNA also stimulated tRNA export. tRNA export itself
displays positive cooperative export kinetics that are abrogated
by saturating concentrations of rRNA. The authors suggest these
results are consistent with the existence of common high
affinity RNA-binding sites that can be titrated with tRNA, rRNA
or ribosomal subunits, and mRNA. Furthermore, high
concentrations of tRNA are also shown to have moderate
inhibitory effects on 40 S subunit export, indicating a lower
affinity common intermediate also shared by mRNA. N.J. Pokrywka
and D.S. Goldfarb: J. Biol. Chem. 1995 270:3619.

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3. CHROMOSOME CONFORMATION AND LOCI INTERACTIONS

J. Dekker et al (Harvard University, US) discuss chromosome
conformation, the authors making the following points:

1) Important chromosomal activities have been linked with both
structural properties and spatial conformations of chromosomes.
Local properties of the chromatin fiber influence gene
expression, origin firing, and DNA repair (1, 2). Higher order
structural features -- such as formation of the 30-nm fiber,
chromatin loops and axes, and interchromosomal connections --
are important for chromosome morphogenesis and also have roles
in gene expression and recombination. Activities such as
transcription and timing of replication have been related to
overall spatial nuclear disposition of different regions and
their relationships to the nuclear envelope (3-5). At each of
these levels, chromosome organization is highly dynamic, varying
both during the cell cycle and among different cell types.

2) Analysis of chromosome conformation is complicated by
technical limitations. Electron microscopy, while affording high
resolution, is laborious and not easily applicable to studies of
specific loci. Light microscopy affords a resolution of 100 to
200 nm at best, which is insufficient to define chromosome
conformation. DNA binding proteins fused to green fluorescent
protein permit visualization of individual loci, but only a few
positions can be examined simultaneously. Multiple loci can be
visualized with fluorescence in situ hybridization (FISH), but
this requires severe treatment that may affect chromosome
organization.

3) In summary: The authors describe an approach to detect the
frequency of interaction between any two genomic loci.
Generation of a matrix of interaction frequencies between sites
on the same or different chromosomes reveals their relative
spatial disposition and provides information about the physical
properties of the chromatin fiber. This methodology can be
applied to the spatial organization of entire genomes in
organisms from bacteria to human. Using the yeast Saccharomyces
cerevisiae, the authors confirm known qualitative features of
chromosome organization within the nucleus and dynamic changes
in that organization during meiosis. The authors also analyzed
yeast chromosome III at the G1 stage of the cell cycle. The
authors report they found that chromatin is highly flexible
throughout. Furthermore, functionally distinct AT- and GC-rich
domains were found to exhibit different conformations, and a
population-average 3D model of chromosome III could be
determined. Chromosome III emerges as a contorted ring.

References (abridged):

1. C. L. Woodcock and S. Dimitrov, Curr. Opin. Genet. Dev. 11,
130 (2001)

2. A. Wolffe, Chromatin, Structure and Function (Academic Press,
San Diego, CA, 1998)

3. E. D. Andrulis, A. M. Neiman, D. C. Zappulla, R. Sternglanz,
Nature 394, 592 (1998)

4. T. Cremer and C. Cremer, Nature Rev. Genet. 2, 292 (2001)

5. S. M. Gasser, Cell 104, 639 (2001)

Science 2002 295:1306

Web Links: chromosome conformation

Related Background Brief:

PERINUCLEAR LOCALIZATION OF CHROMATIN FACILITATES
TRANSCRIPTIONAL SILENCING. Transcriptional silencing in
Saccharomyces cerevisiae at the HM mating-type loci and
telomeres occurs through the formation of a heterochromatin-like
structure. HM silencing is regulated by cis-acting elements,
termed silencers, and by trans-acting factors that bind to the
silencers. These factors attract the four SIR (silent
information regulator) proteins, three of which (SIR2-4) spread
from the silencers to alter chromatin, hence silencing nearby
genes. The authors demonstrate that an HMR locus with a
defective silencer can be silenced by anchoring the locus to the
nuclear periphery. This was accomplished by fusing integral
membrane proteins to the GAL4 DNA-binding domain and
overproducing the hybrid proteins, causing them to accumulate in
the endoplasmic reticulum and the nuclear membrane. The authors
report they expressed the hybrid proteins in a strain carrying
an HMR silencer with GAL4-binding sites (UAS(G)) replacing
silencer elements, causing the silencer to become anchored to
the nuclear periphery and leading to silencing of a nearby
reporter gene. This silencing required the hybrids of the GAL4
DNA-binding domain with membrane proteins, the UAS(G) sites and
the SIR proteins. The authors suggest their results indicate
that perinuclear localization helps to establish
transcriptionally silent chromatin. E.D. Andrulis et al: Nature
1998 395:525.

Related Background Brief:

COMMUNICATION BETWEEN HOMOLOGOUS CHROMOSOMES: GENETIC
ALTERATIONS AT A NUCLEASE-HYPERSENSITIVE SITE CAN ALTER MITOTIC
CHROMATIN STRUCTURE AT THAT SITE BOTH IN CIS AND IN TRANS. In
vegetatively growing diploid strains of the yeast Saccharomyces
cerevisiae, homologous chromosomes appear to be paired via
multiple interstitial interactions, likely as a regular feature
of the diploid lifestyle. The authors have previously suggested
that this pairing is guided by direct physical interactions
between intact DNA duplexes in nuclease hypersensitive regions
and that homology is sensed directly at the DNA level. As a
first test of this idea, the authors have examined the level of
DNase I sensitivity at a prominent nuclease-hypersensitive site
in mitotic chromatin in strains that are either homozygous or
heterozygous for a pair of alleles at this site. The authors
report they find that the degree of nuclease sensitivity at this
site on a given (maternal or paternal) chromosome can vary
depending upon whether the homologue carries the same allele or
the different allele. The data are suggestive that nuclease
sensitivity is higher in the former case than in the latter, as
though nuclease hypersensitivity might be increased when the two
alleles match as compared to when they do not. The authors
conclude that these observations suggest that homologous
chromosomes can communicate via a mechanism that senses the
status of the assayed nuclease-hypersensitive site with
resultant changes in chromatin structure at that site. The
observed pattern of effects is fully compatible with direct
physical interactions between homologues at
nuclease-hypersensitive regions, but alternative scenarios also
can be envisioned. Since DNase I hypersensitive sites occur in
many important regions of chromosomes, homology-dependent
interactions involving such regions could potentially affect
diverse processes including gene expression (e.g. transvection),
chromosome organization, domain structure, and/or DNA
replication patterns. S. Keeney and N. Kleckner: Genes Cells
1996 1:475.

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4. MARS: THE CRUSTAL DICHOTOMY

Sean C. Solomon (Carnegie Institution Washington, US) discuss
the surface of Mars, the author making the following points:

1) A surprising finding from the exploration of Mars by orbiting
spacecraft in the 1970s was that the southern and northern
hemispheres have very different surfaces. The density of impact
craters seen in images taken by Mariner 9 and Viking Orbiter
indicated that the surface of the topographically high southern
hemisphere is old enough to have preserved the effects of the
early, heavy impact bombardment of the inner Solar System (known
from lunar studies to have occurred before about 3.7 billion
years ago). The surface of the northern hemisphere, in contrast,
was revealed to be generally lower in elevation, to consist of
smooth plains, and to contain a far lower density of impact
features -- implying a surface age hundreds of millions to
billions of years younger.

2) A new view of this striking hemispherical contrast, the
Martian "crustal dichotomy", has come from an analysis of
observations collected by the Mars Global Surveyor spacecraft,
which has been in Martian orbit since 1997. From subtle
signatures in topography measured by the Mars Orbiter Laser
Altimeter Experiment(1), Frey and others(2) have identified a
large population of nearly buried impact structures in both
hemispheres that were not evident in the spacecraft images. More
importantly, the areal density of these features, together with
those previously mapped, indicates that the northern hemisphere
has a buried surface that is essentially as old as the surface
of the southern uplands.

3) Frey and colleagues(2) took the following approach in their
search for buried impact features: From regional altimetric
maps, in which different colors were assigned to narrow
intervals of elevation from a global gridded data set, the group
catalogued all roughly circular, localized depressions. They
identified such depressions as candidate impact features if
concentric segments of contours collectively totaled at least
180 degrees of arc, and if the preserved relief exceeded 50 m --
a figure much larger than the altimetry accuracy(1) of about a
meter. Many of the features so catalogued had been identified as
impact craters from orbiter images. However, many others had
not. In particular, Frey et al. counted 644 potential impact
features greater than 50 km in diameter in the northern
lowlands, many more than the 90 such features discernible from
Viking Orbiter images. A strong argument that most, if not all,
of the newly identified features are largely buried impact
craters is that their areal density as a function of their
diameter has the same form as the distribution for known impact
structures. The southern highlands also contain buried impact
craters newly recognized by this method, but they do not
increase the total population of impact structures by as large a
factor as in the north.

4) In summary: Mars has a north–south divide in the age of its
surface, as judged by the density of impact craters. Altimetry
data, which by inference provide a subsurface view of the
planet, reveal that the divide is only skin deep(3-5).

References (abridged):

1. Smith, D. E. et al. J. Geophys. Res. 106, 23689-23722 (2001)

2. Frey, H. V., Roark, J. H., Shockey, K. M., Frey, E. L. &
Sakimoto, S. E. H. Geophys. Res. Lett. 29, 10.1029/2001GL013832
(2002).

3. McGill, G. E. J. Geophys. Res. 94, 2753-2759 (1989)

4. Smith, D. E. et al. Science 284, 1495-1503 (1999)

5. Zuber, M. T. et al. Science 287, 1788-1793 (2000)

Nature 2002 418:27

Web Links:  Mars Mariner 9 Viking Orbiter

Related Background Brief:

THE GLOBAL TOPOGRAPHY OF MARS AND IMPLICATIONS FOR SURFACE
EVOLUTION. Elevations measured by the Mars Orbiter Laser
Altimeter have yielded a high-accuracy global map of the
topography of Mars. Dominant features include the low northern
hemisphere, the Tharsis province, and the Hellas impact basin.
The northern hemisphere depression is primarily a
long-wavelength effect that has been shaped by an internal
mechanism. The topography of Tharsis consists of two broad
rises. Material excavated from Hellas contributes to the high
elevation of the southern hemisphere and to the scarp along the
hemispheric boundary. The present topography has three major
drainage centers, with the northern lowlands being the largest.
The two polar cap volumes yield an upper limit of the present
surface water inventory of 3.2 to 4.7 million cubic kilometers.
D.E. Smith et al: Science 1999 284:1441.

Related Background Brief:

INTERNAL STRUCTURE AND EARLY THERMAL EVOLUTION OF MARS FROM MARS
GLOBAL SURVEYOR TOPOGRAPHY AND GRAVITY. Topography and gravity
measured by the Mars Global Surveyor have enabled determination
of the global crust and upper mantle structure of Mars. The
planet displays two distinct crustal zones that do not correlate
globally with the geologic dichotomy: a region of crust that
thins progressively from south to north and encompasses much of
the southern highlands and Tharsis province and a region of
approximately uniform crustal thickness that includes the
northern lowlands and Arabia Terra. The strength of the
lithosphere beneath the ancient southern highlands suggests that
the northern hemisphere was a locus of high heat flow early in
Martian history. The thickness of the elastic lithosphere
increases with time of loading in the northern plains and
Tharsis. The northern lowlands contain structures interpreted as
large buried channels that are consistent with northward
transport of water and sediment to the lowlands before the end
of northern hemisphere resurfacing. M.T. Zuber et al: Science
2000 287:1788.

Related Background Brief:

WATER AND THE MARTIAN LANDSCAPE. Over the past 30 years, the
water-generated landforms and landscapes of Mars have been
revealed in increasing detail by a succession of spacecraft
missions. Recent data from the Mars Global Surveyor mission
confirm the view that brief episodes of water-related activity,
including glaciation, punctuated the geological history of Mars.
The most recent of these episodes seems to have occurred within
the past 10 million years. These new results are anomalous in
regard to the prevailing view that the Martian surface has been
continuously extremely cold and dry, much as it is today, for
the past 3.9 billion years. Interpretations of the new data are
controversial, but explaining the anomalies in a consistent
manner leads to potentially fruitful hypotheses for
understanding the evolution of Mars in relation to Earth. V.R.
Baker: Nature 2001 412:228.

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5. ON ELECTRONIC EXCITATIONS

Giovanni Onida (University of Rome, IT) discusses electronic
excitations, the author making the following points:

1) In every spectroscopic experiment one perturbs the sample (by
incoming photons, electrons, etc.) and measures the response of
the system to this perturbation. In other words, the system is
excited. Therefore it is in general not sufficient to calculate
ground-state properties in order to interpret or predict results
of experiments like photoemission, electron-energy loss,
absorption, etc.

2) Direct and inverse photoemission and absorption can be taken
as the prototype spectroscopies which one would like to describe
in this context. In the photoemission process, the system
absorbs a photon, and an electron is ejected whose kinetic
energy is then measured at some distance. If one considers this
photoelectron to be completely decoupled from the sample, energy
and momentum conservation allow one to deduce the change in
total energy of the sample, which is interpreted as the energy
level of the "hole", i.e., the level that was formerly occupied
by the photoelectron. Hence as a first approach one can state
that photoemission measures the density of occupied states. By
analogy, inverse photoemission yields information about the
density of unoccupied states. In absorption experiments, an
electron is excited from an occupied state into a conduction
state. This process looks, at first glance, like the sum of a
photoemission and an inverse photoemission experiment (creation
of a hole and an electron). Instead, in the absorption
measurement the excited electron remains inside the system and
cannot be supposed to be a free electron decoupled from the
others. Hence whereas direct and inverse photoemission results
are often already well described by the density of occupied and
unoccupied states, respectively, one realizes that (i) in
absorption, the joint density of occupied and unoccupied states
must be considered, (ii) even over a small range of excitation
energies, transition probabilities can vary considerably and
must be taken into account, and (iii) the excited electron and
the hole cannot be treated separately, since the electron feels
the presence of the hole. Point (iii) constitutes the main
difficulty for a correct description of this type of experiment.

3) The interpretation of photoemission spectra as a density of
occupied states is linked to the picture of independent
electrons which occupy some well-defined energy level in the
system. Of course, electrons are not independent, and it is
clear that, for example, an electron that leaves the sample will
lead the remaining electrons to relax. This relaxation energy
and other quantum-mechanical contributions must be taken into
account if energy differences are to be calculated
correctly.(1-5)

References (abridged):

1. Dobson, J., G. Vignale, and M. P. Das, 1997, Eds., Electronic
Density Functional Theory: Recent Progress and New Directions
(Plenum, New York)

2. Dreizler, R. M., and E. K. U. Gross, 1990, Density Functional
Theory: An Approach to the Quantum Many-Body Problem (Springer,
Berlin).

3. Farid, B., 1999a, in Electron Correlation in the Solid State,
 N.H. March (ed.) (World Scientific, Imperial College), p.  103.

4. Fetter, A. L., and J. D. Walecka, 1971, Quantum Theory of
Many-Particle Systems (McGraw-Hill, New York).

5. Grabo, T., T. Kreibich, S. Kurth, and E. K. U. Gross, 2000a,
in Strong Coulomb Correlations in Electronic Structure: Beyond
the Local Density Approximation, edited by V. I. Anisimov
(Gordon & Breach, Tokyo), pp. 203-211.

Rev. Mod. Phys. 2002 74:601

Web Links: electronic excitations        photoemission

Related Background:

IN FOCUS: ON GRATINGS, SPECTROSCOPY, AND HENRY ROWLAND

"The precision of spectroscopy depends ultimately upon the
precision of some human being's hand and eye. In a research
spectroscope, a diffraction grating rather than the familiar
prism disperses the radiant energy of light. This is a flat or
spherically curved slab of mirrored glass from which the light
is diffracted by parallel lines -- hence the term grating --
scratched on the reflecting surface. The resolution of a grating
-- the narrowness and faintness of the spectral lines it
captures -- is a function of the number of lines per inch and
the exactitude with which they are spaced in the scratching.
Until the advent of electronic feedback control technology
following the Second World War, the perfection of spectroscopy
was owing to the pleasure that Henry Augustus Rowland
[1848-1901] found in contending with physical reality, after the
manner of Galileo, with bare hands. His tangible legacy is 1000
of the most perfect diffraction gratings and a million or more
precisely established spectral lines in the catalogue recorded
from them. The founding professor of physics, at age 27 in 1875,
at Johns Hopkins University, Rowland acted on his determination
to get the foundation work of spectroscopy done quickly and
precisely. He settled on a standard of 14,400 two-inch lines of
identical width and depth, to be plowed in the mirrored surface
exactly parallel to one another across each inch and at exactly
the same spacing from one another across a width of five or six
inches. To eliminate the focusing lens and the loss of light it
would entail, he hit on the self-focusing spherical surface.
Rowland once boasted that he never saw a machine that he did not
immediately understand. He recognized that to make the perfect
"ruling engine" to rule the perfect grating required the
perfection of the critical engine part: the lead screw that
would advance a diamond stylus exactly 1.44 x 10^(-4) inches at
each step across a stretch of five or six inches. At 20 threads
to the inch, each full rotation of the screw would advance the
diamond stylus of his ruling engine one-twentieth of an inch;
each of the 720 settings in each rotation advanced it 1.44 x
10^(-4) inches. To grind the perfect thread in the 9-inch lead
screw, Rowland invented a new machine tool. This was an
11-inch-long grinding or lapping nut with the same threading,
which he split lengthwise in four sections. With the segments
reassembled around the screw, he could adjust the tightness of
the nut through the course of grinding with emery powder and oil
and finally the rouge used to polish telescope mirrors. 'Now
grind the screw in the nut,' Rowland wrote, 'making the nut pass
backwards and forwards over the whole screw... Turn the nut end
for end every ten minutes and continue for two weeks.' In that
time the high spots on the threading of the nut and the screw
found one another and wore themselves away."

Gerard Piel: The Age of Science: What Scientists Learned in the
20th Century  (Basic Books, New York 2001, p.54)

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6. ON ELECTRICAL MEASUREMENT AND THE QUANTUM-CLASSICAL TRANSITION

D. Mozyrsky and L. Martin (Los Alamos National Laboratory, US)
discuss quantum-classical transitions, the authors making the
following points:

1) There is a dramatic difference in the observed behaviors of
microscopic particles and of macroscopic objects. The
everyday-scale objects obey the rules of classical Newtonian
mechanics, while microscopic particles command the use of
quantum physics for their description. The effects of quantum
coherence are almost never observed at the macroscale. The only
known  exceptions are realized when the macroscopic quantum
state is particularly robust against external influences, as is
the case for superconductors and quantum Hall liquids. Hence, it
appears natural to assume that it is the coupling to the
external world, or environment, that leads to decoherence and,
consequently, to a transition from quantum to classical
behavior. Indeed, it has been demonstrated that within
phenomenological models of coupling to environment (or heat
bath), at sufficiently high temperatures, quantum systems lose
their phase coherence and evolve according to the rules of
classical statistical mechanics [1,2].

2) Another important distinction between classical and quantum
systems is in their response to measurement. Measurement of a
classical system, in principle, can have no effect on its state;
on the other hand, in the quantum regime, observation is
inevitably a source of decoherence [3]. Recently, the dephasing
effect of measurement was explicitly demonstrated within several
models of electrical devices measuring finite state systems
[4,5]. The authors report an extension of this approach to the
problem of measurement of a quantum oscillator, which, unlike
the systems considered previously, has a classical counterpart.
The authors demonstrate that, despite the apparent differences
between coupling to a high-temperature heat bath and the
zero-temperature measurement process, the nonequilibrium noise
introduced by the measurement also induces a quantum-classical
transition.

3) Specifically, the authors consider an oscillator coupled to
an electrical tunnel junction. Prom the solution of the combined
problem, the authors separately extract the dynamics of the
oscillator and of the current through the contact. For the
oscillator, the main findings are that (i) current shot noise
generates fluctuations and decoherence, (ii) coupling to the
tunneling electrons leads to dissipation with a damping
coefficient independent of the applied voltage, and (iii) the
oscillator behavior becomes effectively classical with the
temperature equal to one-half of the voltage drop across the
junction. For the tunnel junction, the authors determine the
nonlinear current-voltage (I-V) characteristic, which implicitly
measures the effects of the quantum heating and quantum
dissipation in the oscillator.

4) In summary: A model of an electrical tunnel junction coupled
to a mechanical system (oscillator) was studied to simulate the 
dephasing effect of measurement on a quantum system. The problem
was solved at zero temperature under conditions of strong
nonequilibrium in the measurement apparatus. For linear coupling
between the oscillator and tunneling electrons, it was found
that the oscillator dynamics becomes damped, with the effective
temperature determined by the voltage drop across the junction.
It is demonstrated that both the quantum heating and the quantum
damping of the oscillator manifest themselves in the
current-voltage characteristic of the tunnel junction.

References (abridged):

1. K. Mohring and U. Smilansky, Nucl. Phys. A338, 227 (1980); W.
H. Zurek, Phys. Rev. D 24, 1516 (1981); E. Joos and H. D. Zeh,
Z. Phys. B 59, 223 (1985); T. Bhattacharya, S. Habib, and K.
Jacobs, Phys. Rev. Lett. 85, 4852 (2000).

2. A.O. Caldeira and A.J. Leggett, Physica (Amsterdam) 121A, 587
(1983); A.O. Caldeira and A.J. Leggett, Ann. Phys. (N.Y.) 149,
374 (1983).

3. M. Namiki, S. Pascazio, and H. Nakazato, Decoherence and
Quantum Measurements (World Scientific, Singapore, 1997).

4. S. A. Gurvitz, Phys. Rev. B 56, 15 215 (1997); S. A. Gurvitz
and Ya. S. Prager, Phys. Rev. B 53, 15 932 (1996).

5. A. Shnirman, G. Schon, and Z. Hermon, Phys. Rev. Lett. 79,
2371 (1997).

Phys. Rev. Lett. 2002 89:018301

Web Links: quantum decoherence        quantum-classical
transition

Related Background:

ENTANGLEMENT, DECOHERENCE, AND THE QUANTUM-CLASSICAL BOUNDARY

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 (*Physical Review* 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.

Serge Haroche (Ecole Normale Superieure Paris, FR) reviews
quantum mechanical entanglement, decoherence, and the question
of the boundary between the physics of quantum phenomena and the
physics of classical phenomena. Haroche makes the following
points:

1) In quantum mechanics, a particle can be delocalized
(simultaneously occupy various probable positions in space), can
be simultaneously in several energy states, and can even have
several different identities at once. This apparent "weirdness"
behavior is encoded in the wave function of the particle.

2) Recent decades have witnessed a rash of experiments designed
to test whether nature exhibits implausible nonlocality. In such
experiments, the wave function of a pair of particles flying
apart from each other is entangled into a non-separable
superposition of states. The quantum formalism asserts that
detecting one of the particles has an immediate effect on the
other, even if they are very far apart, even far enough apart to
be out of interaction range. The experiments clearly demonstrate
that the state of one particle is always correlated to the
result of the measurement performed on the other particle, and
in just the strange way predicted by quantum mechanics.

3) An important question is: Why and how does quantum weirdness
disappear (decoherence) in large systems? In the last 15 years,
entirely solvable models of decoherence have been presented by
various authors (e.g., Leggett, Joos, Omnes, Zeh, Zurek), these
models based on the distinction in large objects between a few
relevant macroscopic observables (e.g., position or momentum)
and an "environment" described by a huge number of variables,
such as positions and velocities of air molecules, number of
black-body radiation photons, etc. The idea of these models,
essentially, is that the environment is "watching" the path
followed by the system (i.e., interacting with the system), and
thus effectively suppressing interference effects and quantum
weirdness, and the result of this process is that for
macroscopic systems only classical physics obtains.

4) In mesoscopic systems, which are systems between macroscopic
and microscopic dimensions, decoherence may occur slowly enough
to be observed. Until recently, this could only be imagined in a
gedanken experiment, but technological advances have now made
such experiments real, and these experiments have opened this
field to practical investigation.

PhysicsToday 1999 July

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7. ON MAIL-BORNE TRANSMISSION OF ANTHRAX

G.F. Webb and M.J. Blaser (Vanderbilt University, US) discuss
mail-borne transmission of anthrax, the authors making the
following points:

1) Anthrax has been a scourge of humans and domesticated animals
since ancient times, and its causative agent, Bacillus
anthracis, has long been considered a weapon of biological
warfare or terrorism (1,2). Spores of B. anthracis can survive
indefinitely in a wide range of environments (3), and a
relatively modest dose delivered to mammalian skin or lungs can
result in cutaneous or inhalational anthrax, respectively (4,5).
Gastrointestinal anthrax also occurs in certain regions of the
world, although inhalational anthrax is the most lethal form.

2) Since October 2001, both inhalational and cutaneous cases of
anthrax have been recognized in the United States, after a
hiatus of more than 20 years. Of the 22 cases reported to date
(December 15, 2001), 11 have been cutaneous and 11 have been
inhalational; 5 persons with inhalational anthrax have died,
with a case fatality rate of 45%. All cases of inhalational
anthrax have occurred in persons above 43 years of age (median
56 years, range 43 to 94). After a 1979 accident at a Soviet
factory producing anthrax spores in Sverdlovsk, a city of 1.2
million people, 79 persons were reported to have developed
inhalational anthrax, and 68 of these died (1). All of the cases
were clustered in a single quadrant of the city and its
outskirts, corresponding to the area downwind of the plume
released from the factory. Despite the large number of persons
of all ages potentially exposed to this plume, no cases were
reported in persons <24 years old (1). Both the Russian accident
(1) and the current U.S. cases suggest that older persons have
increased risk for contracting inhalational anthrax after
environmental exposure.

3) Most of the current U.S. cases have been traced to letters
heavily contaminated with anthrax spores that were sent through
the U.S. mail. All strains recovered from mail and from clinical
specimens reportedly have the same molecular fingerprint,
indicating their dissemination from a single source. These
mail-related cases have occurred among the intended recipients
of the letters or others in their work environment (n = 7), or
among postal workers (n = 11). In addition, there have been four
other cases, two cutaneous, and two inhalational (both fatal) in
elderly women, in which the victims appear unrelated to either
the intended recipients or the postal milieu.

4) The authors propose that these "unrelated" cases occurred as
a result of their receiving mail that had been
cross-contaminated as a consequence of heavily contaminated
letters traversing the postal system, as has been considered by
the investigating authorities. To explain these cases, the
authors have developed a mathematical model based on
probabilistic assumptions concerning the proliferation of
contaminated letters through the postal system, and the
infection of recipients of these letters. The model allows
analysis of risk at sequential steps in the pathways of the
mail, and of vulnerabilities of our postal system that require
immediate attention. Analysis of the results generated by this
model suggests practical steps for improving safety.

References (abridged):

1. Meselson, M. , Guillemin, J. , Hugh-Jones, M. , Langmuir, A.,
Popova, I. , Shelokov, A. & Yampolskaya, O. (1994) Science 266,
1202-1208

2. Inglesby, T. V. , Henderson, D. A. , Bartlett, J. G. ,
Ascher, M. S. , Eitzen, E. , Friedlander, A. M. , Hauer, J. ,
McDade, J., Osterholm, M. T. , O'Toole, T. , et al. (1999) J.
Am. Med. Assoc. 281, 1735-1745

3. Manchee, R. J. , Broster, M. G. , Melling, J. , Henstridge,
R. M. & Stagg, A. J. (1981) Nature (London) 294, 254-255

4.  Glassman, H. N. (1966) Bacteriol. Rev. 30, 657-659

5.  Watson, A. & Keir, D. (1994) Epidemiol. Infect. 113, 479-490

Proc. Nat. Acad. Sci. 2002 99:7027

Web Links:  anthrax

Related Background:

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 Queda 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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8. ON PREECLAMPSIA

K.Y. Lain and J.M. Roberts (University of Pittsburgh, US)
discuss preeclampsia, the authors making the following points:

1) Preeclampsia is a pregnancy-specific form of hypertension
that presents a major health problem worldwide. Preeclampsia
complicates 5% to 8% of all pregnancies and increases both
maternal and neonatal morbidity and mortality.(1,2) The mainstay
of therapy for preeclampsia remains clinical recognition through
prenatal care and termination of the disease process with
delivery. Maternal mortality has been reduced in the US, but in
countries where prenatal care is not adequate,
preeclampsia/eclampsia accounts for 40% to 80% of maternal
deaths, an estimated 50,000 per year. Many of these deaths may
be preventable with prenatal care and evidence-based
prophylactic seizure therapy.

2) Infants of women with preeclampsia have a 5-fold increase in
mortality compared with infants of mothers without the disorder.
Much of the neonatal mortality is attributable to iatrogenic
prematurity. Approximately 10% of preeclampsia occurs before 34
weeks gestational age, and indicated delivery for preeclampsia
is responsible for 15% of preterm US births.(3) In developing
countries, perinatal mortality is further increased. Advances in
the understanding of preeclampsia are essential to guide
preventive and therapeutic strategies to decrease the worldwide
impact of this disease.

3) Hypertensive disorders of pregnancy antedate pregnancy and
are specific to pregnancy. The nonspecific term
pregnancy-induced hypertension is not recommended. Gestational
hypertension is defined as only gestational blood pressure
elevation, without proteinuria, and complicates approximately 6%
of pregnancies.2 Gestational blood pressure elevation is blood
pressure greater than 140 mm Hg (systolic) or 90 mm Hg
(diastolic) in a woman who was normotensive before 20 weeks
gestation. This group is a heterogeneous mix of patients:
patients with unrecognized chronic hypertension, transient
hypertension of pregnancy that will resolve postpartum, and
patients developing preeclampsia.(4) Gestational hypertension
with minimally elevated blood pressure and without proteinuria
is not a reliable indicator of maternal or fetal morbidity or
mortality but mandates close attention to mother and fetus.(5)

4) Preeclampsia is defined as gestational blood pressure
elevation with proteinuria4 and usually occurs after 20 weeks of
gestation. Proteinuria is defined as the urinary excretion of
300 mg or greater of protein in a 24-hour period. Because of
poor specificity, edema and incremental blood pressure increases
are no longer included in the diagnosis of preeclampsia.(4)
Nonetheless, it is recommended that pregnant women with an
increase in blood pressure that does not achieve 140 mm Hg
(systolic) or 90 mm Hg (diastolic) warrant close observation.(4)
Likewise, patients who have gestational hypertension without
proteinuria but with other evidence of new end-organ involvement
should be managed as if they have preeclampsia. Eclampsia is the
occurrence of seizures that cannot be otherwise explained in a
woman with preeclampsia.

References (abridged):

1. ACOG. Diagnosis and management of preeclampsia and eclampsia.
ACOG Practice Bulletin. 2002;33:1-14.

2. Sibai BM, Ewell M, Levine RJ, et al. Risk factors associated
with preeclampsia in healthy nulliparous women: the Calcium for
Preeclampsia Prevention (CPEP) study group [see comments]. Am J
Obstet Gynecol.1997;177:1003-1010.

3. Goldenberg RL, Rouse DJ. Prevention of premature birth. N
Engl J Med. 1998;339:313-320.

4. Report of the national high blood pressure education program
working group on high blood pressure in pregnancy. Am J Obstet
Gynecol. 2000;183:S1-S22.

5. Brown MA, Wang M-X, Buddle ML, et al. Albumin excretory rate
in normal and hypertensive pregnancy. Clin Sci (Colch).
1994;86:251-255.

J. Am. Med. Assoc. 2002 287:3183

Web Links:  preeclampsia eclampsia

Related Background Brief:

REPORT OF THE NATIONAL HIGH BLOOD PRESSURE EDUCATION PROGRAM
WORKING GROUP ON HIGH BLOOD PRESSURE IN PREGNANCY. This report
updates the 1990 "National High Blood Pressure Education Program
Working Group Report on High Blood Pressure in Pregnancy" and
focuses on classification, pathophysiologic features, and
management of the hypertensive disorders of pregnancy. Through a
combination of evidence-based medicine and consensus this report
updates contemporary approaches to hypertension control during
pregnancy by expanding on recommendations made in "The Sixth
Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure." The
recommendations to use Korotkoff phase V for determination of
diastolic pressure and to eliminate edema as a criterion for
diagnosing preeclampsia are discussed. In addition, the use as a
diagnostic criterion of blood pressure increases of 30 mm Hg
systolic or 15 mm Hg diastolic with blood pressure <140/90 mm Hg
has not been recommended, because available evidence shows that
women with blood pressures fitting this description are not more
likely to have adverse outcomes. Management distinctions are
made between chronic hypertension that is present before
pregnancy and hypertension that occurs as part of the
pregnancy-specific condition of preeclampsia, as well as
management considerations for women with comorbid conditions. A
discussion of the pharmacologic treatment of hypertension during
pregnancy includes recommendations for specific agents. The use
of low-dose aspirin, calcium, or other dietary supplements in
the prevention of preeclampsia is described, and expanded
sections on counseling women for future pregnancies and
recommendations for future research are included. Am J Obstet
Gynecol 2000 183:S1.

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9. AN EVALUATION OF RADICAL BREAST CANCER SURGERY

B. Fisher et al (University of Pittsburgh, US) discuss breast
cancer surgery, the authors making the following points:

1) The Halsted radical mastectomy, an en bloc removal of the
breast, muscles of the chest wall, and contents of the axilla,
was the "established and standardized operation for cancer of
the breast in all stages, early or late"(1) for most of the 20th
century. However, by the mid-1960s, dissatisfaction with results
after radical mastectomy and anecdotal information regarding
other procedures led some surgeons to advocate more extensive
surgery and others to promote more limited operations.(2) New
information about tumor metastases also suggested that less
radical surgery might be just as effective as the more extensive
operations that were being performed.(3)

2) To help resolve the clinical controversy, the National
Surgical Adjuvant Breast and Bowel Project (NSABP) initiated the
B-04 clinical trial in August 1971. The aims of the study were
to determine whether patients with either clinically negative or
clinically positive axillary nodes who received local or
regional treatments other than radical mastectomy would have
outcomes similar to those achieved with radical mastectomy.
Previous findings from this trial demonstrated differences in
control of local disease but failed to show a significant
difference in either survival free of distant disease or overall
survival among the groups of women with negative nodes or
between the groups of women with positive nodes.(4,5) The
25-year findings reported by the authros support the earlier
results.

3) A total of 1079 women with clinically negative axillary nodes
underwent radical mastectomy, total mastectomy without axillary
dissection but with postoperative irradiation, or total
mastectomy plus axillary dissection only if their nodes became
positive. A total of 586 women with clinically positive axillary
nodes either underwent radical mastectomy or underwent total
mastectomy without axillary dissection but with postoperative
irradiation.

4) The authors conclude: "The findings validate earlier results
showing no advantage from radical mastectomy. Although
differences of a few percentage points cannot be excluded, the
findings fail to show a significant survival advantage from
removing occult positive nodes at the time of initial surgery or
from radiation therapy."

References (abridged):

1. Bloodgood JC. Problems of cancer. J Kansas Med Soc
1930;31:311-6.

2. Fisher B. The surgical dilemma in the primary therapy of
invasive breast cancer: a critical appraisal. Curr Probl Surg
1970;:3-53.

3. Fisher B. Laboratory and clinical research in breast cancer
-- a personal adventure: the David A. Karnofsky Memorial
Lecture. Cancer Res 1980;40:3863-3874.

4. Fisher B, Montague E, Redmond C, et al. Comparison of radical
mastectomy with alternative treatments for primary breast
cancer: a first report of results from a prospective randomized
clinical trial. Cancer 1977;39:Suppl:2827-2839.

5. Fisher B, Gebhardt MC. The evolution of breast cancer
surgery: past, present, and future. Semin Oncol 1978;5:385-394.

New Engl. J. Med. 2002 347:567

Web Links: breast cancer surgery

Related Background:

ON BREAST CANCER

L. Sivaraman et al (Baylor College of Medicine, US) discuss
breast cancer. The lifetime risk of developing breast cancer
among Western women is approximately 10 percent, and despite
advances in therapeutic strategies, breast cancer remains the
leading cause of cancer deaths in women in most developed
countries. It is expected that ultimately prevention of breast
cancer will be achieved with better understanding of the
etiological factors contributing to the development of the
disease. There is significant evidence that the timing of normal
developmental events like menarche, menopause, and age of first
full-term pregnancy (parity) have a significant impact on an
individual's susceptibility to breast cancer. In particular,
there is strong epidemiological evidence that women who
experience a full-term pregnancy early in their lives have a
significantly reduced risk for developing breast cancer. This is
recapitulated in rat models that demonstrate that early
full-term pregnancy confers resistance ("refractoriness") to
chemical carcinogen-induced mammary tumorigenesis. This
protection can be mimicked with the hormones estrogen and
progesterone, or human choriogonadotropin given either before or
immediately after carcinogen challenge to induce a refractory
state (i.e., a state resistant to tumorigenesis). But despite a
wealth of literature supporting the role of endocrinological
processes in mediating parity-related refractoriness to
tumorigenesis, the cellular and molecular mechanisms that
underlie hormone-induced refractoriness are largely unresolved.

Proc. Nat. Acad. Sci. 2001 98:12379

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10. ON CATALYTIC CONVERTERS AND AUTOMOTIVE EMISSION CONTRAL.

Y. Nishihata et al (Japan Atomic Energy Research Institute, JP)
discuss catalytic converters, the authors making the following
points:

1) Catalytic converters are widely used to reduce the amounts of
nitrogen oxides, carbon monoxide and unburned hydrocarbons in
automotive emissions. The catalysts are finely divided
precious-metal particles dispersed on a solid support. During
vehicle use, the converter is exposed to heat, which causes the
metal particles to agglomerate and grow, and their overall
surface area to decrease. As a result, catalyst activity
deteriorates. The problem has been exacerbated in recent years
by the trend to install catalytic converters closer to the
engine, which ensures immediate activation of the catalyst on
engine start-up, but also places demanding requirements on the
catalyst's heat resistance. Conventional catalyst systems thus
incorporate a sufficient excess of precious metal to guarantee
continuous catalytic activity for vehicle use over 50,000 miles
(80,000 km).

2) The authors report they use X-ray diffraction and absorption
to show that LaFe(0.57)Co(0.38)Pd(0.05)O(3) (Pd-perovskite), one
of the perovskite-based catalysts investigated(1-4) for
catalytic converter applications since the early 1970s, retains
its high metal dispersion owing to structural responses to the
fluctuations in exhaust-gas composition that occur in
state-of-the-art petrol engines(5). The authors find that as the
catalyst is cycled between oxidative and reductive atmospheres
typically encountered in exhaust gas, palladium (Pd) reversibly
moves into and out of the perovskite lattice. This movement
appears to suppress the growth of metallic Pd particles, and
hence explains the retention of high catalyst activity during
long-term use and ageing.

3) A state-of-the-art automotive petrol engine is operated close
to the stoichiometric air-to-fuel ratio (by using an oxygen
sensor and a sophisticated feedback control system linked to the
catalyst) in order to convert simultaneously three pollutant
emissions -- carbon monoxide (CO), hydrocarbons, and nitrogen
oxides (NOx)5 -- into carbon dioxide (CO2) water (H2O) and
nitrogen (N2). A time lag associated with adjusting the
air-to-fuel ratio results in a redox fluctuation in the exhaust
gas. The authors designed their catalyst system to react to this
fluctuation, to achieve greater efficiency and to conserve
precious metals.

References (abridged):

1. Meadowcroft, D. B. Low-cost oxygen electrode material. Nature
226, 847-848 (1970)

2. Libby, W. F. Promising catalyst for auto exhaust. Science
171, 499-500 (1971)

3. Tanaka, H., Fujikawa, H. & Takahashi, I. Perovskite-Pd
Three-Way Catalysts for Automotive Applications (SAE Paper
930251, Society of Automotive Engineers, Inc., Warrendale,
Pennsylvania, 1993)

4. Tanaka, H., Fujikawa, H. & Takahashi, I. Excellent Oxygen
Storage Capacity of Perovskite-Pd Three-Way Catalysts (SAE Paper
950256, Society of Automotive Engineers, Inc., Warrendale,
Pennsylvania, 1995)

5. Heck, R. M. & Farrauto, R. J. Catalytic Air Pollution
Control: Commercial Technology 94-102 (Van Nostrand Reinhold,
New York, 1995)

Nature 2002 418:164

Web Links: catalytic converters

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11. ON PHOTOLUMINESCENCE PROPERTIES OF NANOCRYSTALS

L. Qu and X. Peng (University of Arkansas, US) discuss
nanocrystals, the authors making the following points:

1) Colloidal semiconductor nanocrystals have generated great
fundamental and technical interest in recent years.(1-3) The
size-dependent emission is probably the most attractive property
of semiconductor nanocrystals. For example, by one simple
synthetic scheme, it is possible to synthesize differently sized
CdSe nanocrystals that emit from blue to red with very pure
color. These nanocrystal-based emitters can be used for many
purposes, such as light-emitting diodes,(4,5) lasers, biomedical
tags, etc. For this reason, the control of the photoluminescence
properties of semiconductor nanocrystals has been a major goal
for developing synthetic chemistry for colloidal semiconductor
nanocrystals.

2) The emission properties of semiconductor nanocrystals can be
characterized by four fundamental parameters, which are the
brightness, the emission color, the color purity, and the
stability of the emission. Due to quantum size effects,(3) the
band gap of CdSe nanocrystals increases as their size decreases,
and thus the emission color of the band-edge photoluminescence
of the nanocrystals shifts continuously from red (centered at
650 nm) to blue (centered at 450 nm) as the size of the
nanocrystals decreases. Since the emission color of
semiconductor nanocrystals is strongly dependent on size(3) and
shape, the color purity of the emission becomes dependent on the
size and shape distribution of a nanocrystal sample. Therefore,
the control of the emission color and color purity is likely a
matter of the control of the size/shape and size/shape
distribution of the semiconductor nanocrystals, regarding which
recent studies have provided a reasonable knowledge basis. The
other two parameters, however, cannot yet be correlated with
certain structural parameters or some adjustable growth
conditions of a given synthetic scheme. As a result, the
photoluminescence brightness, measured by photoluminescence
quantum yield, and the stability of the emission of the
as-prepared semiconductor nanocrystals are not easy to predict
and generally vary from synthesis to synthesis.

3) CdSe nanocrystals with close to monodisperse size
distribution and high crystallinity became available in the
early 1990s by use of dimethylcadmium as the cadmium precursor.
This organometallic approach has been well developed during the
past 10 years in terms of the control over the size, shape, and
size/shape distribution of the resulting CdSe nanocrystals. The
recently introduced alternative routes with safe and inexpensive
cadmium precursors and ligands promoted the synthesis of CdSe
nanocrystals to an easily adoptable level. In principle, with
knowledge regarding the control over the size/shape and
size/shape distribution of the CdSe nanocrystals, the emission
color and the purity of the color can be controlled to a certain
extent. At present, the purity of the emission color of a CdSe
nanocrystal sample is still significantly worse than that of the
single particle emission.

References (abridged):

1. Heath, J. R., Ed. Acc. Chem. Res. 1999 (Special Issue for
Nanostructures, review articles relevant to colloidal
nanocrystals.)

2. Alivisatos, A. P. Science 1996, 271, 933-937

3. Brus, L. E. J. Chem. Phys. 1986, 90, 2555

4. Sundar, V. C.; Lee, J.; Heine, J. R.; Bawendi, M. G.; Jensen,
K. F. Adv. Mater. 2000, 12, 1102

5. Schlamp, M. C.; Peng, X. G.; Alivisatos, A. P. J. Appl. Phys.
1997, 82, 5837-5842

J. Am. Chem. Soc. 2002 124:2049

Web Links: nanocrystals photoluminescence

Related Background Brief:

ELECTRONIC WAVE FUNCTIONS IN SEMICONDUCTOR CLUSTERS: EXPERIMENT
AND THEORY. Recent experimental and theoretical work in the
size-dependent development of bulk electronic properties in
semiconductor crystallites of approximately 15 to several
hundred are critically reviewed and discussed. Semiconducting
electronic properties are explained in chemical valence
terminology. These crystallites can be termed "clusters" because
they are too small to have bulk-like electronic wave functions
even though they exhibit bulk-like crystal structure. The
principal experimental evidence comes from the recent discovery
that liquid-phase precipitation reactions can be controlled to
make and stabilize crystalline semiconductor clusters in this
size range. The cluster electronic properties can be studied
optically in dilute colloidal solutions. The cluster internal
crystal structure is directly revealed by transmission electron
microscopy. The results indicate that the approach of cluster
electronic wave functions to the bulk Bloch molecular orbitals
is exceedingly slow as a function of cluster size. This result
can be analytically predicted in terms of the intrinsic electron
delocalization present in crystalline materials with strong,
directional chemical bonding. L. Brus: J. Phys. Chem. 1986
90:2555

Related Background:

SYNTHESIS OF NANOCRYSTALS

K.J. Ziegler et al (University of Texas Austin, US) discuss the
synthesis of nanocrystals. At the nanometer length-scale,
material dimensions lead to quantum confinement effects that
give rise to unique electronic and optical properties useful for
a variety of new technologies including electronic, optical,
medical, coatings, catalytic, memory, and sensor applications. A
variety of wet chemical methods have been developed for
nanocrystal synthesis. The main issues are control over particle
size and size distribution, *surface passivation, and core
crystallinity. Metal nanocrystals, such as those of silver and
gold, can be synthesized at room temperatures in
high-boiling-point solvents to achieve crystalline cores and
well-defined shape. The key ingredient in all of these methods
is the use of "capping" ligands that bind to particle surfaces
and provide a steric barrier to aggregation. The capping ligands
tend to exhibit the properties of surfactants: one end binds
strongly to the particle surface, while the opposite end
interacts with the solvating fluid. In a good solvent, the
ligands extend from the nanocrystal surface and provide steric
stabilization, which typically limits size to the nanometer
range and prevents unwanted agglomeration. *Supercritical fluids
offer several processing advantages over conventional solvents,
which has led to their increased use in materials chemistry, and
more specifically to their use in nanocrystal synthesis.

J. Am. Chem. Soc. 2001 123:7797

Notes:

 *surface passivation: In general, "passivation" is a surface
reaction producing a protective layer that prohibits further
reaction. For example, aluminum reacts spontaneously with oxygen
in air to form a thin layer of aluminum oxide, which then
prevents further oxidation.

 *Supercritical fluids: In general, a "supercritical fluid" is
any fluid at a temperature and pressure above its critical
point. In general, in this context, the "critical point" is the
value of temperature/pressure at which the properties of the
liquid and gaseous states of the fluid are identical.

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12. ON GRAIN BOUNDARIES IN HIGH-TEMPERATURE SUPERCONDUCTORS

In this context, the term "grain boundary" refers to an
interface between individual crystals in a polycrystalline solid.

H. Hilgenkamp and J. Mannhart (University of Twente, NL) discuss
grain boundaries in high-T superconductors, the authors making
the following points:

1) After the enthusiasm following the discovery of
high-temperature (high Tc) superconductivity, it was realized
that applications of these materials are exceedingly difficult
to achieve. The reasons for these difficulties are rooted in the
fundamental physics of high-temperature superconductors, which
directly determines the properties of interfaces in these
compounds: the ultrashort coherence length of a few angstroms
seemed to preclude the realization of high-quality Josephson
junctions, and the small critical current density of
polycrystalline samples, a few hundred A/cm^(2) at 4.2 K,
apparently ruled out the fabrication of useful high-temperature
wires.

2) The properties of polycrystalline high-temperature 
superconductors are influenced in a complex manner by a large
variety of interfaces, such as grain or twin boundaries. To
understand the behavior of bulk polycrystals, information about
the properties of individual and well-defined interfaces is
required. Owing to the complexity of the problem, however, it is
challenging to understand the superconducting properties of
individual interfaces by analyzing polycrystalline samples. To
unveil the basic properties of the interfaces, the "bicrystal"
technology was invented, which allows single, well-defined grain
boundaries to be fabricated and analyzed in thin-film samples.
Bicrystal experiments readily yielded several intriguing results
(see, for example, Mannhart and Chaudhari, 2001): as suspected
in the original paper on high-Tc superconductivity (Bednorz and
Miiller, 1986), grain boundaries generally limit the critical
current densities of polycrystalline high-Tc samples. But
large-angle boundaries also form excellent Josephson junctions.
Characterized by these properties, grain boundaries in the
high-Tc superconductors differ fundamentally from their
counterparts in classical metallic superconductors and in MgB2.
Those boundaries are electronically much less active and act as
pinning sites at most (see, for example, DasGupta et al., 1978).
To take advantage of the unusual properties of the boundaries in
the high-Tc superconductors, other techniques besides bicrystal
technology, such as biepitaxial growth or the step-edge
technology, have been developed and widely applied.

3) Owing to their universal, largely compound-independent
properties, grain boundaries in high-Tc superconductors are of
central importance for numerous applications, ranging from
high-current-carrying cables to electronic circuits and sensors,
from rf devices operating in the THz range to superconducting
quantum interference devices (SQUIDs). For many experiments
aimed at elucidating the physics of high-Tc superconductivity,
for example, attempts to identify the order-parameter symmetry
of the cuprates or to search for time-reversal symmetry
breaking, grain boundaries have also been used with outstanding
success.(1-5)

References (abridged):

1. Alarco, J., Y. Boikov, G. Brorsson, T. Claeson, G. Daalmans,
J. Edstam, Z. Ivanov, V. K. Kaplunenko, P. A. Nilsson, E.
Olsson, H. K. Olsson, J. Ramos, E. Stepantsov, A. Tzalenchuk, D.
Winkler, and Y-M. Zhang, 1994, "Engineered grain boundary
junctions—characteristics, structure, applications," in  
Materials and Crystallographic Aspects of HT-Superconductivity,
edited by E. Kaldis (Kluwer Academic, Dordrecht), pp. 471-490.

2. Albrecht, J., S. Leonhardt, and H. Kronmuller, 2000a,
"Influence of vortex-vortex interaction on critical currents
across low-angle grain boundaries in YBa2Cu307-a thin films,"
Phys. Rev. B 63, 014507.

3. Aiff, L., A. Beck, R. Gross, A. Marx, S. Kleefisch, Th.
Bauch, H. Sato, M. Naito, and G. Koren, 1998, "Observation of
bound surface states in grain-boundary junctions of
high-temperature superconductors," Phys. Rev. B 58, 11197-11200.

4. Aiff, L., R. Gerdemann, K. D. Husemann, A. Beck, T. Trauble,
B. Mayer, and R. Gross, 1993, in Applied Superconductivity,
Proceedings EUCAS '93, edited by H. C. Freyhardt (DGM
Informationsgesellschaft mbH, Oberursel, Germany), pp. 1199-1202.

5. Amin, M. H. S., A. N. Omelyanchouk, and A. M. Zagoskin, 2001,
"Mechanisms of spontaneous current generation in an
inhomogeneous d-wave superconductor," Phys. Rev. B 63, 212502.

Rev. Mod. Phys. 2002 74:485

Web Links: grain boundaries in crystals

Related Background:

ON THE DISCOVERY OF HIGH TEMPERATURE SUPERCONDUCTIVITY

One of the operating tenets of 20th century "big science" is
that important breakthroughs in science can be more or less
engineered if appropriate conditions are constructed and
appropriate individual researchers placed in those conditions.
When this approach produces a success, the various bureaucrats
who support the idea feel reaffirmed; when various
counter-examples to the approach occur, it is the turn of the
doubters to feel reaffirmed. A cogent instance of a
counter-example was provided in 1986 by the Bednorz-Mueller
discovery of high-temperature superconductivity -- a discovery
of signal importance in experimental physics made by two
relatively unknown researchers working in what can be
characterized as a backwater and poorly-equipped laboratory. Not
only was the discovery of high-temperature superconductivity
totally unexpected by the international physics community, but
the discovery of the phenomenon by outsiders under "little
science" conditions caused a degree of shock in the science
policy system. Ordinary superconductivity is a property of many
metals, alloys, and chemical compounds at temperatures near
absolute zero, at which temperatures (their "critical
temperatures") their electrical resistivity vanishes and they
become strongly diamagnetic. (Diamagnetic substances such as the
alkalis and alkaline earth metals, the halogens, and the noble
gases are repelled by magnets and tend to position themselves at
right angles to the magnetic lines of force.) High-temperature
superconductors were unknown until 1986, but at present there
are some known high-temperature superconductors with critical
temperatures greater than 100 kelvins. The accepted theory of
ordinary superconductivity is the Bardeen-Cooper-Schrieffer
theory (BCS theory) (1957). At the present time, a successful
theory of high-temperature superconductivity has not been
developed, in spite of a great deal of effort. Johannes Georg
Bednorz (1950- ) and K. Alexander Mueller (1927- ) shared the
Nobel Prize in Physics in 1987 for their discovery of
high-temperature superconductivity in a ceramic oxide
(lanthanum-barium-copper) alloy at 30 degrees kelvin, at that
time the highest superconductivity temperature ever observed,
the work having been carried out at the IBM Zurich Research
Laboratories at Rueschlikon.

Helga Nowotny (Swiss Federal Institute of Technology, CH)
presents an essay on innovation in research and the modern
partnership between basic research and applied science, the
author making the following points:

1) One of the most exciting recent success stories of science
began in September 1986 with the appearance in the _Zeitschrift
fur Physik_ of an article with the cautious title, "Possible
high-Tc superconductivity in the Ba-La-Cu-O system." A few weeks
later, the names of the two authors, Alexander Mueller and Georg
Bednorz, and their discovery hit the front pages of _The New
York Times_ and researchers around the world were caught in an
unprecedented frenzy, attempting to replicate and surpass the
findings of the initial breakthrough. The race for
high-temperature superconducting systems was on.

2) The discovery of high-temperature superconductivity was
unexpected in terms of its discoverers, the place of its
discovery, and the scientific ideas involved. It contradicted
conventional wisdom and the expectations of peers and research
administrators. Mueller and Bednorz were outsiders, Mueller a
specialist on perovskites (a type of oxide mineral) and Bednorz
a crystallographer. They benefited from the novice effect, but
they also enjoyed a degree of autonomy that allowed them to
prepare for the unpredictable. Of the 3 superconductivity
laboratories of IBM, the Rueschlikon laboratory where the two
researchers were based was by far the most modestly equipped.
And the discovery contradicted long-held views, not only
overturning certain established empirical rules concerning
superconductivity, but also unveiling previously unknown
phenomena not accounted for by the classic
Bardeen-Cooper-Schrieffer theory.

3) The author points out that even if we knew how to create
conditions under which creativity can flourish, and how to favor
the occurrence of what cannot be planned, the problem remains of
how to turn highly individualistic bursts of scientific
creativity into socially desired techno-scientific outcomes.
"For the most disturbing paradox is this: there has been a
relative decline in the importance of the individual creative
act, while its proliferation is encouraged. Individual
scientific creativity has become a necessary, but no longer
sufficient, precondition in a long, branching sequence of
possibilities."

Nature 1999 401:859

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