ScienceWeek

ScienceWeek - June 14, 2002
Vol. 6 Number 24

An Online Research Digest Published Weekly Since 1997

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

The tendency has always been strong to believe that whatever
received a name must be an entity or being, having an
independent existence of its own. And if no real entity
answering to the name could be found, men did not for that
reason suppose that none existed, but imagined that it was
something peculiarly abstruse and mysterious.
-- Stephen Jay Gould (1941-2002)

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

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

Section 1

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

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

1. Chemistry: On Chiral Interactions

2. On Bell Inequalities and Quantum Entanglement

3. On Free-Electron Lasers 

4. Geoscience: On the Atlantic Thermohaline Circulation 

5. On Glacial Climate Instability 

6. On Quantum Identity 

7. On Organ Development 

8. On Recognition of Native-Like Protein Structures 

9. On Myosin Motor Proteins

10. On the Interaction of Water with Biological Macromolecules

11. History of Single-Molecule Recordings in Biology 

12. Biological vs. Engineering Complexity 

13. On Defect Turbulence 

14. On the Development of Enzyme Mimics 

15. Current-Induced Forces in Molecular Wires 

16. On Magnetic Refrigerants 

17. On Nuclear Warheads 

18. On 3-dimensional X-Ray Structural Microscopy

19. On DNA in Bacterial Biofilms 

20. On Misallocation of Credit in Science 

21. On Hybridization and Extinction 

22. Aspects of Nuclear Radiation Terrorism

23. On Global Climate Change and Health 

24. Association Between Duration of Breastfeeding and Adult
Intelligence 

25. In Focus: On Becquerel's Discovery 

26. ScienceWeek Notices and Subscription Information

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

Section 2

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

1. CHEMISTRY: ON CHIRAL INTERACTIONS

In general, chirality is a property of certain asymmetric
objects such that the object and its mirror image cannot be
superimposed one on the other while both objects are restricted
to the same plane (e.g., a left- and right-handed glove). In
chemistry, chiral molecules are optically active, a phase of
each form rotating the plane of incident polarized light. The
two possible forms are called "optical isomers", and each form
is called an "enantiomer". An equal mixture of the two forms is
called a "racemic mixture". "Homochirality" is the preference of
a process or system for a single optical isomer in a pair of
isomers. Optically active substances are termed "dextrorotatory"
(the D- form; the + form) or "levorotatory" (the L- form; the -
form) according to whether the plane of polarization of the
incident polarized light is rotated to the right or to the left
with respect to the direction of incidence of the light. In
biology, one of the great puzzles is that nearly all amino acids
in biological systems are of the L- form, while nearly all
sugars are of the D- form (glycine is the only biological amino
acid that is not chiral), and the puzzle is how did this arise?

I. Katsuki et al (Kumamoto University, JP) discuss chiral
interactions, the authors making the following points:

1) Since the historic discovery of spontaneous resolution in
ammonium sodium tartrate by Louis Pasteur (1), chirality has
been an important topic in chemistry, pharmacy, and living
organisms (2-4). Chirality is expressed at both the molecular
and supramolecular levels (5). The initial progress in chirality
was in the generation of molecular chirality from the reaction
of achiral components, which developed into assembling isolated
chiral molecules. When a chiral molecule aggregates and
crystallizes, it can form either (a) a racemic compound, (b) a
conglomerate (racemic mixture), or (c) a racemic solid solution.
Jacques et al (1981) reported that, statistically, between 5 and
10% of all racemates form conglomerate crystals, indicating that
homochiral interaction in the formation of crystalline racemates
is usually weaker than heterochiral interaction.

2) Although the formation of conglomerates vs racemic compounds
is determined by the laws of physics under specific conditions,
these laws are not yet fully understood, and therefore the
formation of conglomerates cannot be predicted a priori. If
enantioselective homochiral molecular discrimination arising
from substantially strong, selective, and directional
interactions, such as a coordination bond or a hydrogen bond,
can be extended from two adjacent molecules to one-dimensional
(1D), 2D, and 3D systems, then a conglomerate exhibiting 3D
intermolecular homochiral interaction, and hence showing
spontaneous resolution on crystallization, would be achieved.
The question to be answered in the most essential and difficult
step toward this purpose is, "How can we design a particular
molecule exhibiting an intermolecular homochiral interaction and
a multidimensional extended structure?"

References (abridged):

1. Pasteur, L. Ann. Chim. Phys. 1848, 24, 442-459.

2. (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
John Wiley & Sons: New York, 1994. (b) Palyi, G.; Zucchi, C.;
Caglitoti, L. Advances in Biochirality; Elsevier: Oxford, 1999.

3. Prins, L. J.; Huskens, J.; Jong, F.; Timmerman, P.;
Reinhoudt, D. N. Nature 1999, 398, 498-502.

4. Soo, J.; Whang, D. Lee, H.; Jun, S. I.; Oh, J.; Jeon, Y. J.;
Kim, K. Nature 2000, 404, 982-986.

5. Lehn, J.-M. Supramolecular Chemistry, Concepts and
Perspectives; VCH: Weinheim, 1995.

J. Am. Chem. Soc. 2002 124:629

ScienceWeek http://www.scienceweek.com

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

2. ON BELL INEQUALITIES AND QUANTUM ENTANGLEMENT

In this context, "locality" is essentially the proposition that
the speed of light is the ultimate limit at which interactions
between different locations can occur. The term "local reality"
refers to the assumption of the existence of a real physical
world consisting of real particles that exist even when not
observed.

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

A "hidden variables theory" is one of a class of physical
theories which deny that the quantum state of a physical system
is a complete specification. The hidden variables are those
components of the hypothetical complete state that are not
contained in the quantum state. "Bell's inequality", formulated
by John Bell (1928-1990) in 1964, is one of a family of
inequalities concerning the probabilities of joint occurrence of
certain events in two well- separated parts of a composite
system, the inequality implied by any hidden variables theory
that satisfies an appropriate locality condition. "Bell's
theorem" is the theorem that no hidden variables theory
satisfying an appropriate locality condition can make
statistical predictions in complete agreement with those of
quantum mechanics. In other words, there are situations in which
quantum mechanics predicts a violation of Bell's inequality.
Another formulation is that any hidden variables theory that
forbids instantaneous interactions cannot make predictions in
complete agreement with those of quantum mechanics.

A. Acin (University of Barcelona, ES) discusses quantum
entanglement, the author making the following points:

1) Nonlocality or entanglement is one of the most striking
properties of quantum mechanics. From a fundamental point of
view, its importance is related to the fact that no
local-realistic theory is able to reproduce the correlations
observed in some entangled states of composite systems.
Moreover, recent results in quantum information theory show that
it is also a useful resource for information transmission and
processing. The author demonstrates a connection between these
two features of entangled states.

2) In their seminal work of 1935 [2], Einstein, Podolsky, and
Rosen pointed out a conflict between the correlations appearing
in some quantum states of composite systems and local-realistic
theories. Later, Bell [3] derived some conditions, known as Bell
inequalities, that are satisfied by any local-realistic theory,
but that are violated for some quantum states. The experimental
check of the violation of these inequalities [4] confirmed that
it is not possible to build a local hidden variable model
reproducing all the correlations observed for quantum states of
composite systems (see also [5]). Thus, quantum mechanics is
said to be non-local. For pure states, a Bell inequality is
violated if and only if the state is not separable. For mixed
states the picture is not as clear.

References (abridged):

2. A. Einstein, B. Podolsky, and N. Rosen, Phys. Rev. 47, 777
(1935).

3. J.S. Bell, Physics, 1, 195 (1964).

4. A. Aspect, J. Dalibard, and G. Roger, Phys. Rev. Lett. 49,
1804 (1982).

5. W. Tittel, J. Brendel, H. Zbinden, and N. Gisin, Phys. Rev.
Lett. 81, 3563 (1998); G. Weihs, T. Jennewein, C. Simon, H.
Weinfurter, and A. Zeilinger, Phys. Rev. Lett. 81, 5039 (1998);
M.A. Rowe, D. Kielpinski, V. Meyer, C. A. Sackett, W. M. Itano,
C. Monroe, and D. J. Wineland, Nature (London) 409, 791 (2001).

Phys. Rev. Lett. 2002 88:027901

ScienceWeek http://www.scienceweek.com

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

3. ON FREE-ELECTRON LASERS

In this context, a "free electron" is an electron detached from
any atom.

W.B. Colson et al (Naval Postgraduate School, US) discuss
free-electron lasers, the authors making the following points:

1) Free-electron lasers contain only the essential ingredients
for light amplification by stimulated emission: a beam of
electrons, an external magnetic field to deflect them, and laser
light. They dispense with nonessentials like the atomic nuclei
and their bound electrons that impose limitations on
conventional atomic lasers. The gain medium of the free-electron
laser is transparent to all wavelengths, and the physics of the
gain mechanism is essentially the same for all wave-lengths from
a centimeter down to an angstrom.

2) The free-electron laser uses a beam of relativistic electrons
passing through a periodic, transverse magnetostatic field _ the
"wiggler" field _ to amplify the laser light beam propagating
along the axis of the electron beam (1). A typical infrared
free-electron laser uses a beam of 50-MeV electrons, delivered
as a train of picosecond pulses separated by many nanoseconds.
The peak current within a pulse is usually of order 10 A and the
diameter of the electron beam is typically about a millimeter.
The electron beam energy is "pumped" through the free-electron
laser interaction volume at nearly the speed of light. The laser
light is stored between the resonator mirrors as fresh electrons
from the accelerator enter the wiggler. Traversing the wiggler,
they contribute about 1% of their power to the copropagating
light beam. The spent electron beam exits the wiggler without
leaving behind any waste heat. That is another advantage free
electron lasers have over conventional lasers.

3) Most often, the wiggler is constructed from a series of
permanent magnets with a period of a few centimeters over about
100 periods. By the time the electrons reach the end of the
wiggler, they have become bunched in such a way that they
amplify the copropagating light by radiating coherently with it.
The light beam moves slightly faster than the relativistic
electrons. Free-electron laser resonance is achieved when one
wavelength of light passes over an electron in the time it takes
the electron to traverse one period of the wiggler.

References (abridged):

1. P. O'Shea, H. Freund, Science 292, 1853 (2001). C. Brau,
Free-Electron Lasers, Academic Press, Boston (1990).

Physics Today 2002 January

ScienceWeek http://www.scienceweek.com

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

4. GEOSCIENCE: ON THE ATLANTIC THERMOHALINE CIRCULATION

In general, a "thermohaline circulation" is a vertical
circulation induced by the cooling of surface waters in a large
water body, this cooling causing convective overturning and
consequent mixing of waters. In the oceans, this circulation
usually involves temperature and salinity variations acting
together.

In this context, a "geostrophic current" is a current
controlled by a balance between a pressure-gradient force and
the Coriolis effect. The Coriolis effect is an apparent force
that arises because of the Earth's spin around its axis. Freely
moving objects are deflected to the right of their direction of
motion in the Northern Hemisphere and to the left of their
direction of motion in the Southern Hemisphere. The force is
proportional to the speed and latitude of the moving object, and
thus varies from zero at the equator to a maximum at the poles.

P.U. Clark et al (Oregon State University, US) discuss the
Atlantic thermohaline circulation, the authors making the
following points:

1) The ocean affects climate through its high heat capacity
relative to the surrounding land, thereby moderating daily,
seasonal and interannual temperature fluctuations, and through
its ability to transport heat from one location to another. In
the North Atlantic, differential solar heating between high and
low latitudes tends to accelerate surface waters polewards,
whereas freshwater input to high latitudes together with
low-latitude evaporation tend to brake this flow. Today, the
former thermal forcing dominates the latter haline (freshwater)
forcing and the meridional overturning in the Atlantic drives
surface waters northward, while deep water that forms in the
Nordic Seas flows southward as North Atlantic Deep Water. This
thermohaline circulation is responsible for much of the total
oceanic poleward heat transport in the Atlantic, peaking at
about 1.2 +- 0.3 PW (1 PW equals 10^(15) watts) at 24 degrees N
(1).

2) No such deep overturning occurs in the North Pacific, where
surface waters are too fresh to sink (2). The lack of a
meridional land barrier in the Southern Ocean precludes the
existence of strong east-west pressure gradients needed to
balance a southward geostrophic surface flow, so that poleward
heat transport associated with the thermohaline circulation is
small there. Deep-water formation in the Southern Ocean occurs
along the Antarctic continental shelf in the Weddell and Ross
Seas either through intense evaporation or, more typically,
through brine rejection that produces dense water that sinks
down and along the slope (3). In addition, supercooled water may
be formed at the base of the thick floating ice shelves during
freezing or melting and this dense water may in turn flow
downslope (4).

3) The idea that the Atlantic thermohaline circulation may have
many speeds is now a century old (2), but not until the 1960s
did a quantitative, albeit idealized, framework emerge to
explain the physics behind the potential existence of these
multiple equilibria (5). Subsequently, ocean and coupled
atmosphere-ocean general circulation models were shown to
support multiple equilibria. Such studies have revealed that
multiple equilibria exist because the atmosphere responds to
anomalies of sea surface temperature, but not salinity. They
have further shown that transitions between different states are
often abrupt and can be induced through small perturbations to
the hydrological cycle.

4) In summary: The possibility of a reduced Atlantic
thermohaline circulation in response to increases in
greenhouse-gas concentrations has been demonstrated in a number
of simulations with general circulation models of the coupled
ocean-atmosphere system. But it remains difficult to assess the
likelihood of future changes in the thermohaline circulation,
mainly owing to poorly constrained model parameterizations and
uncertainties in the response of the climate system to
greenhouse warming. Analyses of past abrupt climate changes help
to solve these problems. Data and models both suggest that
abrupt climate change during the last glaciation originated
through changes in the Atlantic thermohaline circulation in
response to small changes in the hydrological cycle. Atmospheric
and oceanic responses to these changes were then transmitted
globally through a number of feedbacks. The paleoclimate data
and the model results also indicate that the stability of the
thermohaline circulation depends on the mean climate state.

References (abridged):

1. Ganachaud, A. & Wunsch, C. Improved estimates of global ocean
circulation, heat transport and mixing from hydrographic data.
Nature 408, 453-457 (2000).

2. Weaver, A. J., Bitz, C. M., Fanning, A. F. & Holland, M. M.
Thermohaline circulation: High latitude phenomena and the
difference between the Pacific and Atlantic. Annu. Rev. Earth
Planet. Sci. 27, 231-285 (1999).

3. Killworth, P. D. Deep convection in the world ocean. Rev.
Geophys. Space Phys. 21, 1-26 (1983).

4. Grumbine, R. W. A model of the formation of high-salinity
shelf water on polar continental shelves. J. Geophys. Res. 96,
22049-22062 (1991).

5. Stommel, H. Thermohaline convection with two stable regimes
of flow. Tellus 13, 224-230 (1961).

Nature 2002 415:863

ScienceWeek http://www.scienceweek.com

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

5. ON GLACIAL CLIMATE INSTABILITY

A. Schmittner et al (University of Victoria, CA) discuss glacial
climate instability, the authors making the following points:

1) Early analysis of deep cores from the Greenland ice sheet (1,
2) revealed that the North Atlantic climate was much more
variable during the last glacial period than during the present
interglacial. Meanwhile, numerous observational and model
studies implicated that mode changes of the Atlantic
thermohaline circulation were involved in these so-called
Dansgaard-Oeschger (D-O) oscillations (3-5). The reason for the
different variability between glacial and interglacial times,
however, has remained enigmatic, and the forcing mechanisms for
the mode changes are still unknown.

2) The Atlantic thermohaline circulation currently accounts for
up to 1.2 x 10^(15) W of poleward heat transport. Near-surface
currents bring warm saline waters from the subtropics to high
northern latitudes, where they are cooled by the atmosphere,
sink to depths between 2000 and 3000 meters, and flow back south
as a deep western boundary current. Since early pioneering
studies, multiple equilibria of the Atlantic thermohaline
circulation have been found in a hierarchy of models. Relatively
small perturbations to high-latitude surface salinities can lead
to the stabilization of the water column, followed by a
cessation of deep convection and a subsequent abrupt shutdown of
the thermohaline circulation. Sea surface temperatures and sea
surface salinities in the North Atlantic consequently drop by
several degrees and salinity units, respectively, in agreement
with reconstructions of the D-O oscillations (4, 5). The reduced
northward heat flux also leads to a sudden decrease in
near-surface air temperatures in regions adjacent to the North
Atlantic, consistent with proxy records.

3) Although it seems established that perturbations to the North
Atlantic freshwater budget can cause rapid (in less than a
century) climate change, little is known about the origins and
causes of these freshwater perturbations during the last glacial
period.

References (abridged):

1. W. Dansgaard et al., in Climate Processes and Climate
Sensitivity, J. E. Hansen, T. Takahashi, Eds., vol. 29 of
Geophysical Monograph Series (American Geophysical Union,
Washington, DC, 1984), pp. 288-298.

2. H. Oeschger et al., in Climate Processes and Climate
Sensitivity, J. E. Hansen, T. Takahashi, Eds., vol. 29 of
Geophysical Monograph Series (American Geophysical Union,
Washington, DC, 1984), pp. 299-306.

3. W. S. Broecker, D. Peteet, D. Rind, Nature 315, 21 (1985).

4. G. Bond, et al., Nature 365, 143 (1993).

5. T. F. Stocker, Int. J. Earth Sci. 88, 365 (1999).

Science 2002 295:1489

ScienceWeek http://www.scienceweek.com

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

6. ON QUANTUM IDENTITY

Peter Pesic (St. John's College Sante Fe, US) discusses quantum
identity, the author making the following points:

1) Quantum mechanics is the heart of modern physics, the guiding
thread in the maze of atoms and nuclei, the key to understanding
the stability of matter. Despite this, quantum theory remains
enigmatic, for its basic assumptions seem bewildering:
Everything is both wave and particle; uncertainty and
probability rule. Even after a hundred years, both experts and
the general public remain baffled. Albert Einstein called
quantum theory "spooky" and tried to get around it. Paul Dirac
thought that it "cannot even be explained adequately in words at
all," which is why physicists rely so much on the abstract
mathematical structure of the theory. Yet as eminent a physicist
as Freeman Dyson has suggested that, even after one has
struggled to master the formal language of quantum mechanics,
the best that one can do is to say "I understand now that there
isn't anything to be understood."

2) Richard Feynman, a master of finding simple ways to
understand complex ideas, also threw up his hands. After summing
up the basic rules of quantum theory, he confessed that "one
might still like to ask: 'How does it work? What is the
machinery behind the law?' No one has found any machinery behind
the law. No one can 'explain' any more than we have just
'explained.' No one will give you any deeper representation of
the situation. We have no ideas about a more basic mechanism
from which these results can be deduced."

3) The author suggests there is no getting around the difficulty
of quantum theory, which, despite its bizarre character, has
passed every experimental test brilliantly. Yet there may be a
way to view this theory that draws its strangeness into clearer
perspective. The author reports that for 20 years he has been
studying the role of identity and individuality in the history
and foundations of quantum mechanics, and that these studies
have led him to the view that at the heart of quantum theory
lies the radical conception that all elementary particles lack
individuality. Their identities merge and, in so doing, give
rise to the weird world of quantum phenomena. Certainly,,
quantum identity has long been a well-accepted aspect of the
theory, crucial in understanding the chemical bond and the
structure of elements. But it has been considered the
consequence of other and more abstract assumptions, rather than
as the cornerstone of quantum behavior.

References (abridged):

French, S., and M. Redhead. 1988. Quantum physics and the
identity of indiscernibles. British Journal for the Philosophy
of Science 39:233-246.

Gracia, J. J. E. 1988. Individuality: An Essay on the
Foundations of Metaphysics. Albany: State University of New York
Press.

Pesic, P. D. 1991. The principle of identicality and the
foundations of quantum theory. I. The Gibbs paradox. II. The
role of identicality in the formation of quantum theory.
American Journal of Physics 59:971-979.

Pesic, P. D. 2000. Identity and the foundations of quantum
theory. Foundations of Physics Letters 13:55-67.

American Scientist 2002 90:262

ScienceWeek http://www.scienceweek.com

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

7. ON ORGAN DEVELOPMENT

To an engineer with open eyes, the assemblage of parts that
constitute a living organism is an engineering marvel. The
exterior anatomy of an insect, for example, involves a complex
arrangement of numerous parts with specific mechanical and
sensory functions, and this assemblage is replicated with great
precision in the production of each generation. In an ordinary
manufacturing plant, the various parts of a machine are usually
manufactured independently of each other and then the finished
parts assembled according to an external grand plan to produce
the final manufactured product. In a biological organism,
however, the "manufacturing" scheme is quite different: In the
first place, the "grand plan" is internal and not external: each
cell of the organism carries the "grand plan" -- the genome --
with specific parts of the plan activated in each cell type, and
the activation/inactivation of specific parts of the genome are
differentially dynamic in various cell types during the
developmental process. Secondly, during development of the
embryo, body parts are developed in parallel, in tandem, in
sequence, with an intricate network of control loops, until
finally the complete developed product emerges in toto as a
functioning entity. How is this biological development and
assembly process orchestrated? One of the most spectacular
findings of recent years has been that flies and mice use the
same genes for specifying embryonic developmental regions along
the anterior-posterior axis of the body.

In the embryos of higher animals, there occurs the
transformation of a single-layer "blastula" into a 3-layered
"gastrula" consisting of ectoderm (outermost layer), mesoderm
(middle layer), and endoderm (innermost layer) surrounding a
cavity with one opening. The 3 layers are called the "germ
layer", and these layers, via further cell differentiation and
proliferation, determine the development of all the major body
systems and organs. The term "gastrulation" refers to the
process that transforms the single-layered blastula
into the 3-layered gastrula.

C. Thisse and L.I. Zon (Louis Pasteur University, FR) discuss
organogenesis, the authors making the following points:

1) During the evolution of multicellular organisms, the
homeostatic function of organs provided animals with a selective
advantage. In vertebrates, most of organogenesis occurs during
embryonic development and is often completed before birth or
before hatching. At the onset of organ development, cells in the
embryo are associated with one of three germ layers: the
ectoderm, mesoderm, and endoderm (1). Each organ has its
embryonic origins from one of these layers, although distinct
cell populations from each layer will occasionally mix to form
an organ. For instance, the gastrointestinal epithelium is
derived from endoderm, but the intestine also contains
connective tissue and muscle cells that are derived from
mesoderm. This tripartite segregation of germ layers is
associated with the migratory events of gastrulation and is
linked to the spatial and temporal formation (or patterning) of
the embryonic axes. In most vertebrates, the position of the
organs along the dorsal-ventral axis is conserved. The notochord
and muscle are located dorsally, whereas kidney and blood form
in more ventral tissues. The examination of morphological
similarities and differences between animal phyla has been used
historically to develop a basic understanding of organ
development. This comparative approach, taken together with new
molecular and genetic tools, has led to the reevaluation of
classical concepts in the developmental biology of organ
formation.

2) Organs are formed from groups of cells within a developmental
field. The concept of a field implies a homogenous
multipotential stage before differentiation occurs (2-5). Cells
within the field are specified and selected to become a
particular type or lineage. Despite the apparent morphologic
homogeneity, molecular techniques have revealed that cells
within a field can express distinct genes before organ
development, a condition called "prepatterning". Cell lineage
commitment within the field can occur early and quickly. The
specified cells within the field undergo morphogenesis, the
process of cell movement and coalescence as tissues change form.
Morphogenesis is guided by both soluble and cell-associated
ligand-receptor interactions. During or after morphogenesis,
organs form into recognizable units through cell-specific
differentiation and proliferation. As a general rule, the cells
of the embryo remain plastic with respect to cell-specific
commitment until late in the process of organ formation.

3) In summary: Organs are specialized tissues used for enhanced
physiology and environmental adaptation. The cells of the embryo
are genetically programmed to establish organ form and function
through conserved developmental modules. The authors suggest
that the zebrafish is a powerful model system poised to
contribute to our basic understanding of vertebrate
organogenesis. The authors develop the theme of modules and
illustrate how zebrafish have been particularly useful for
understanding heart and blood formation.

References (abridged):

1. R. S. Beddington and J. C. Smith, Curr. Opin. Genet. Dev. 3,
655 (1993).

2. E. M. De Robertis, E. A. Morita, K. W. Cho, Development 112,
669 (1991).

3. J. Huxley, G. de Beer, The Elements of Experimental
Embryology (Cambridge Univ. Press, Cambridge, 1934).

4. L. Wolpert, J. Theor. Biol. 25, 1 (1969).

5. H. Spemann, Roux's Arch. Ent. Mech. 48, 533 (1921) .

Science 2002 295:457

ScienceWeek http://www.scienceweek.com

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

8. ON RECOGNITION OF NATIVE-LIKE PROTEIN STRUCTURES

P. Koehl and M. Levitt (Stanford University, US) discuss protein
structures, the authors making the following points:

1) Knowing the structure of a protein is most useful for
predicting, analyzing, and modifying its function. As it is not
feasible to determine experimentally the structure of every
protein, structure prediction has become central to the field of
structural biology and more specifically to structural genomics.
On the basis of their study of ribonuclease A (1), Anfinsen and
coworkers provided the first clues that all of the information
required for folding a protein is to be found in its sequence.
Not long after this discovery, people took on the challenge of
discovering the rules that allow the protein to fold. This
problem is far from simple and has not yet been solved (2).
Three major routes are usually considered paths to the solution:
homology modeling, threading, and ab initio prediction. To study
a protein with unknown conformation C, the first two methods
follow the same scheme: a similar protein whose
three-dimensional structure is known is identified, and this
protein is used as a scaffold to generate a model for C. When
the sequences of the two proteins are homologous (i.e., when
they have an obvious common ancestry), sequence similarity is
assumed to infer structural similarity (3, 4), and the method is
then referred to as "homology modeling." When the two sequences
show no obvious evolutionary relationship, the method is
referred to as "fold recognition," which works by assessing the
compatibility of the target sequence with each member of a
library of known structures (5).

2) Ab initio structure prediction methods try to build a model
for the target protein structure without using a specific
template protein. Most of these methods proceed by first
generating a large collection of possible conformations
(decoys), which are then searched with a scoring function to
identify native or, more realistically, near-native
conformations. This second step resembles the fold recognition
problem, with the major difference that the library of folds
considered includes computer-generated models instead of
naturally occurring protein folds.

3) In summary: The goal of the inverse protein folding problem
is to identify amino acid sequences that stabilize a given
target protein conformation. Methods that attempt to solve this
problem have proven useful for protein sequence design. The
authors report a demonstration that the same methods can provide
valuable information for protein fold recognition and for ab
initio protein structure prediction. The authors present a
measure of the compatibility of a test sequence with a target
model structure, based on computational protein design. The
model structure is used as input to design a family of low free
energy sequences, and these sequences are compared with the test
sequence by using a metric in sequence space based on
nearest-neighbor connectivity. The authors report that this
measure is able to recognize the native fold of a myoglobin
sequence among different globin folds. It is also powerful
enough to recognize near-native protein structures among
nonnative models.

References (abridged):

1. Anfinsen, C. (1973) Science 181, 223-230

2. Murzin, A. (2001) Nat. Struct. Biol. 8, 110-112

3. Chothia, C. & Lesk, A. (1986) EMBO J. 5, 823-826

4. Sander, C. & Schneider, R. (1991) Proteins Struct. Funct.
Genet. 9, 6-68

5. Jones, D. T. , Taylor, W. R. & Thornton, J. M. (1992) Nature
(London) 358, 86-89

Proc. Nat. Acad. Sci. 2002 99:691

ScienceWeek http://www.scienceweek.com

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

9. ON MYOSIN MOTOR PROTEINS

Fifty years ago, a biologist looking at a large living
biological cell through a light microscope could see motions on
the surface and in the interior of the cell, motions aplenty and
all of it mysterious. It was not until the 1960s that the
microscale structures involved in cell movements were roughly
identified, not until the 1970s that the biochemistry of these
structures was characterized, and not until the 1990s that a
clearer picture of the possible intricate movements of the
"molecular motors" (motor proteins) of living cells became
apparent. An engineer viewing some of the current models of
biological molecular motors will find nanoscale devices
involving only a handful of macromolecules, with each device
engaged in a precise sequence of repetitive movements --
rotations, vibrations, translocations along tracks, linear
contractions, etc. -- the energy for these motions derived from
enzyme-catalyzed reactions, and all of these devices assembled
with apparent great precision by synthetic processes controlled
by information stored in the genome of the cell. It is quite
understandable if the engineer, for example, while looking at a
model of the macromolecular assembly evidently responsible for
the rotation of a flagellum, the whip-like structure involved in
bacterial movement, is flabbergasted. We have apparently crossed
a threshold into a world of nanoscale "machinery" in biological
cells, and cell biology in the 21st century promises to be a
source of extraordinary revelations.

It is now recognized that the interiors of biological cells are
structurally complex, and that this structure is dynamic.
Microtubules are part of the cytoskeleton of biological cells,
the quasi-rigid matrix that among other things determines cell
shape. The microtubules are 25 nanometers in diameter, and
composed of the protein tubulin. They occur in regular arrays in
various cell organelles, and in the cytoplasm in general, and
they contribute not only to cell shape, but also to cell
motility. Microfilaments are 4 to 6 nanometers in diameter,
highly variable in length, and are found in all eukaryotic
cells. They are composed of a protein called "actin" and several
other accessory proteins, and they are important in cell
locomotion and in the molecular dynamics of muscle cells. "Motor
proteins" are mechanico-chemical enzymes involved in locomotion
or transport, and there are three families of such proteins:
kinesins, dyneins, and myosins. Kinesins and dyneins are
microtubule based motor proteins, while myosin is a
microfilament based motor protein. In general, as
mechanico-chemical enzymes, motor proteins convert energy from
hydrolysis of nucleotides to mechanical force, and since they
are involved in many important cellular events, the molecular
details are currently the focus of intensive research.

Myosin is a large protein with a molecular weight of
approximately 500K daltons, and it accounts for approximately
half the protein present in the myofibrils that comprise muscle
fibers. The myosin molecule consists of 6 polypeptide subunits:
2 heavy chains with a molecular weight of approximately 200K
daltons each and 4 light chains of approximately 20K daltons
each. In electron micrographs, purified myosin appears as a long
thin rod containing 2 globular heads protruding at one end. This
2-headed type of mysoin is called "myosin-2" to distinguish it
from the smaller and single-headed myosin-1 molecule involved in
cytoplasmic movements in some non-muscle cells.

Michael A. Geeves (University of Kent, UK) discusses motor
proteins, the author making the following points:

1) Most organisms, whether they consist of a single cell or
billions, can move in a directed way, an ability that is largely
attributed to molecular motor proteins. Of these, myosin-2 is
perhaps the best understood because of its role in muscle
contraction. But other motors from the myosin family are also
required for processes involving motility, from cell division to
the transport of organelles within cells (1). One of the most
hotly debated issues (2) in this field centers on how myosins
move, and a theory known as the "lever-arm hypothesis" has
received much experimental support. This theory proposes that
tiny changes in myosin's "head" portion are amplified by the
adjoining "neck" (the lever arm) to produce large displacements
at the far end of the neck that translate into movement of the
whole protein (3), with the size of the displacement depending
on the length of the lever. Not everyone agrees, however, and
the theory has faced recent challenges.

2) Myosins consist of a head, a neck and a tail. The neck
comprises a structural element identified as an alpha-helix,
often attached to up to six polypeptide chains called light
chains. The tail is involved in connecting the motor to its
cargo, specifying the motor's cellular location and, in some
cases, allowing dimerization. (Myosins 2, 5 and 6, for example,
all consist of two identical proteins, each with its own head,
neck and tail.) The head attaches to and moves along tracks of
actin filaments. These are made up of globular monomers that
string together to form a chain; two chains twist round each
other to form a helical filament.

3) The breakdown of the cell's energy store, adenosine
triphosphate (ATP), powers myosin movement, driving large
structural changes that cause the myosin heads to cyclically
attach and detach from actin. Crystal structures of the myosin
II head show the neck emerging from it, stabilized by two light
chains, at an angle that varies by up to 60 degrees depending on
whether the head is bound to ATP or to the products of ATP
hydrolysis (adenosine diphosphate and phosphate). So the neck
looks like a lever, which led to the idea that it operates as a
rigid body to amplify small structural changes in the myosin
head, with longer necks leading to a larger displacement.
Support for this model comes from studies of myosins engineered
to have lever arms of different length. The results show a
linear relationship between the lever's length and the protein's
speed of moving actin filaments over a surface or step size in
an optical trap.

References (abridged):

1. Myosin Home Page;
http://www.mrc-lmb.cam.ac.uk/myosin/myosin.html 

2. Cyranoski, D. Nature 408, 764-766 (2000).

3. Geeves, M. A. & Holmes, K. C. Annu. Rev. Biochem. 68, 687-728
(1999).

Nature 2002 415:129

ScienceWeek http://www.scienceweek.com

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

10. ON THE INTERACTION OF WATER WITH BIOLOGICAL MACROMOLECULES

Biological molecules such as proteins and DNA contain both
hydrophilic and hydrophobic parts arranged in long chains. The
3-dimensional structures of these molecules are determined by
the way these chains fold into more compact arrangements in
which hydrophilic groups are on the surface where they can
interact with water and hydrophobic groups are buried in the
interior away from water. These local macromolecule solubility
considerations were formulated in 1959 by Walter Kauzman as a
"hydrophobic effect" crucial for protein folding. There are 3
types of water molecules that must be considered in a computer
model of a biological molecule in aqueous solution: a) the
ordered water surrounding and strongly interacting with the
macromolecule; b) the bulk water beyond the ordered water; and,
c) any water molecules that may be buried within the
macromolecule. Computer simulations of DNA in water have
revealed that water molecules are able to interact with nearly
every part of the double helix of DNA, including the nucleotide
base pairs that constitute the genetic code. In contrast, water
is not able to penetrate deeply into the structure of proteins,
whose hydrophobic regions are arranged on the inside into a
close-fitting core. (M. Gerstein and M. Levitt: Scientific
American 1998 November)


S.V. Ruffle et al (UMIST, UK) discuss water interactions with
biological macromolecules, the authors making the following
points:

1) Cells in living organisms are environments that are composed
of very high concentrations of macromolecules such as RNA, DNA,
and protein as well as membranes (1,2). Estimates for protein
concentrations in the cytoplasm of the cell are about 200-300 mg
of protein/mL, leading to a gel-like consistency. The problems
and advantages of maintaining such molecular crowding within the
cellular milieu have been discussed in depth (1,2). Where high
water content is functionally required in cells (e.g., in
generating turgor pressure in plant cells), the bulk water tends
to be segregated into separate compartments in the cell (e.g.,
vacuoles). This suggests that a high macromolecule/low water
situation may be important for cellular function. The concept
that molecular crowding could facilitate many cellular processes
has been explored previously (1,2). Water structure has been
extensively studied in its pure form by neutrons (3-5), but
studies of water-water and water-macromolecule interactions
under conditions similar to those found in the cell are rarer,
despite being of considerable significance.

2) There is a growing body of evidence that the structure and
behavior of water in the vicinity of biological macromolecules
may be different from that of pure water. High-resolution
crystal structures of pure protein or DNA that have been
obtained at cryogenic temperatures have ordered interfacial
water molecules in the electron density maps, and in a few cases
these represent a large fraction of the total solvent content in
the crystals. However, these ordered water molecules do not form
the typical ice Ih structure, but rather are involved in many
different forms of hydrogen bonding networks with the
macromolecule and with each other. If such an altered water
structure exists in the vicinity of macromolecules in cells,
then it has potential significance for a range of fundamental
functions such as protein folding and stability, DNA packaging,
and molecular recognition. Moreover, an understanding of the
interaction of water and macromolecules at cryogenic
temperatures is, in its own right, of considerable importance,
especially for the freezing of cells and tissues without the
irretrievable loss of function.

3) Experimental investigation of water around DNA and proteins
is traditionally difficult. Using diffraction (X-ray or neutron)
techniques is very difficult for this type of study, because
first, although (synchrotron) X-ray diffraction has a better
resolution and luminosity, lack of ability to see protons makes
it very unsuitable for examining the structure of water (the
orientations of water molecules in particular). Neutron
scattering, on the other hand, has the ability to see proton
positions; however, the complex structures of DNA/proteins and
the arrangements of water molecules around them make it very
hard to gain a clear picture of the spatial arrangements, since
averaged (time and molecule) positions are often are given.
However, using neutron vibrational spectroscopy, we can define
the local structures of water molecules by comparing the
vibrational signatures with known configurations in
high-pressure phases of ice (3-5).

4) The authors report they have studied water-DNA and
water-proteolipid membrane systems over a range of hydration
states using inelastic incoherent neutron scattering. The
authors report they find a relatively sharp transition for both
systems at a water concentration above which bulk solvent can be
detected. Below this concentration, bulk water is essentially
absent, i.e., all the water in the system is interacting with
the biological macromolecules. From their results, the authors
conclude that in living organisms a large proportion of the
cellular water will be in a state quite distinct from bulk
water. The authors suggest their data add to the growing
evidence that water structure in the vicinity of biological
macromolecules is unusual and that the proximal water behaves
differently compared to the bulk solvent.

References (abridged):

1. Ellis, J. R. Curr. Opin. Struct. Biol. 2001, 11, 114-119

2. Burg, M. C. Cell Physiol. Biochem. 2000, 10, 251-256

3. Li, J. C.; Ross, D. K. Nature 1993, 365, 327-329

4. Li, J. C. J. Chem. Phys. 1996, 105, 6637-6657

5. Kolesnikov, A. I.; Li, J. C.; Parker, S. F.; Eccleston, R.
S.; Loong, C. K. Phys. Rev. B 1999, 59, 3569-3578

J. Am. Chem. Soc. 2002 124:565

ScienceWeek http://www.scienceweek.com

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

11. ON SINGLE-MOLECULE RECORDINGS IN BIOLOGY

In this context, "patch-clamp recording" is a technique in which
a small patch of cell membrane containing a single or a small
number of ionic channels is drawn up into a blunt hollow glass
microelectrode (micropipette) so that minuscule currents
(picoamperes) flowing through the single channel or through the
several channels can be recorded. The technique was first
perfected in the 1970s by Erwin Neher and Bert Sakmann, and in
1991 they shared the Nobel Prize in Physiology and Medicine for
their work.

Ion channels are protein channels in cell membranes that allow
ions to pass from extracellular solution to intracellular
solution and vice versa. Most ion channels are selective,
allowing only certain ions to pass, and an individual cell has
ion channels with various ion selectivities. The selectivity of
an ion channel can be "gated", the channel effectively opened or
closed, and ion channels are said to *voltage-gated or
*ligand-gated, depending on how the change in selectivity is
provoked.

S. Diez et al (Max Planck Institute of Molecular Cell Biology
and Genetics Dresden, DE) discuss single-biomolecule recording,
the authors making the following points:

1) Observing single molecules at work has been a long-standing
goal of biologists. The first time-resolved recordings from
individual proteins were made in 1976 by Neher and Sakmann (2),
who measured the tiny currents passing through single ion
channels in membranes. The subsequent refinement of the
patch-clamp technique made single-channel electrical recordings
routine, and has led to an explosion of information about the
structure and function of ion channels (3) . But the spectacular
success of the patch-clamp technique relied on the unique
electrical properties of ion channels _ a single channel can
pass ~10^(6) ions per second when open _ and there was no way to
generalize it to other proteins. Thus alternative approaches had
to be found.

2) Motor proteins offered a promising avenue for such studies
because the cytoskeletal filaments along which they move are
huge polymeric molecules, and even the narrow, 6 nanometer
diameter actin filaments could be imaged by darkfield (4) or
fluorescence (5) microscopy. This led to the development of
"up-side-down" motility assays in which motors were bound to a
surface and the movement of filaments across the surface
followed by video microscopy (6); by reducing the density of
motors on the surface it was even possible to record from
individual motor proteins. In order to visualize the movement of
the motor rather than the filament, however, the motor protein
itself has to be labeled. This was first done by binding the
motor to a large, micron-diameter bead. One advantage of this
preparation over the upside-down assay is that the bead (with
attached motor) can be held in an optical trap, making possible
measurements of single-molecule forces and steps. But the
disadvantages are that binding exactly one motor molecule to one
bead is not straightforward, and the method will not be
generally applicable to other proteins or for use within cells.

3) A crucial step towards the development of a general method
for imaging single proteins was made by Funatsu et al (1995):
they pushed the sensitivity of the fluorescence microscope to
the limit of being able to visualize individual myosin molecules
labeled with the fluorophores Cy3 or Cy5. Using total internal
reflection fluorescence microscopy, the processive movement of
individual kinesin molecules along microtubules was visualized
by labeling the motor with Cy-3 or with the green fluorescent
protein (GFP). Fusing GFP to the protein of interest offers
several advantages: it avoids difficult labeling procedures
needed for conventional dyes; expression of GFP-tagged proteins
is possible inside cells; and there is an exact one-fluorophore
to one-protein labeling ratio. The problems with GFP as a
single-molecule marker are that it blinks on and off and has low
photostability.

References (abridged):

2. Neher E. and Sakmann B. (1976) Single-channel currents
recorded from membrane of denervated frog muscle fibres. Nature,
260:799-802.

3. Hille B. Ion Channels of Excitable Membranes. (2001)
Sunderland, Mass: Sinauer Associates.

4. Nagashima H. and Asakura S. (1980) Dark-field light
microscopic study of the flexibility of F-actin complexes. J.
Mol. Biol., 136:169-182.

5. Yanagida T., Nakase M., Nishiyama K. and Oosawa F. (1984)
Direct observation of motion of single F-actin filaments in the
presence of myosin. Nature, 307:58-60.

6. Kron S.J. and Spudich J.A. (1986) Fluorescent actin filaments
move on myosin fixed to a glass surface. Proc. Nat. Acad. Sci.,
83:6272-6276.

Current Biology 2002 12:R203

ScienceWeek http://www.scienceweek.com

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

12. BIOLOGICAL VS. ENGINEERING COMPLEXITY

Although natural selection does not guarantee that organisms
will increase in complexity as they evolve, it is apparent that
the complexity of certain lineages, such as our own, has
increased during evolution. But despite our intuitive notion of
biological complexity -- in terms of morphological or behavioral
complexity, or the variety of cell types in an organism -- the
term itself is notoriously difficult to define. Is the number of
genes in the genome of an organism an appropriate measure of
biological complexity? It has been assumed that eukaryotes have
more genes than bacteria, that animals have more genes than
plants, and that vertebrates have more genes than invertebrates
-- which fits with the traditional idea of a "scala naturae".
But recent completed genome sequences indicate this is not
necessarily the case: surprisingly, it turns out that the
nematode worm C. elegans has 18,424 genes in its genome, the
fruit fly. Drosophila has 13,601 genes, the plant Arabidopsis
approximately 25,498, and humans approximately 35,000 genes.
This suggests there must be other and more sensible genomic
measures of complexity than the mere number of genes.
Transcription factors are DNA binding proteins that switch
target genes on and off. For all transcription factor families,
their members increase in number in the order yeast, nematode,
fruit fly, human. The diversity of cell types in these organisms
also increases in that order. This makes sense, given that
maintaining the differential state of increasingly diverse cell
types requires the presence of more and more molecular switches.
Claverie (2001) has suggested that we define biological
complexity in terms of the number of "transcriptome" states that
the genome of an organism can achieve, with a transcriptome
defined as the complete set of RNA transcripts. (Szathmary et
al: Science 2001 292:1315)

M.E. Csete and J.C. Doyle (University of Michigan, US) discuss
biological complexity, the authors making the following points:

1) The theory and practice of complex engineering systems have
progressed so radically that they often embody Arthur C.
Clarke's dictum, "Any sufficiently advanced technology is
indistinguishable from magic." Systems-level approaches in
biology have a long history (1, 2) but are just now receiving
renewed mainstream attention (3-5), whereas systems-level design
has consistently been at the core of modern engineering,
motivating its most sophisticated theories in controls,
information, and computation. The hidden nature of complexity
("magic") and discipline fragmentation within engineering have
been barriers to a dialog with biology. A key starting point in
developing a conceptual and theoretical bridge to biology is
robustness, the preservation of particular characteristics
despite uncertainty in components or the environment.

2) Biologists and biophysicists new to studying complex networks
often express surprise at a biological network's apparent
robustness. They find that "perfect adaptation" and homeostatic
regulation are robust properties of networks, despite
"exploratory mechanisms" that can seem gratuitously uncertain.
Some even conclude that these mechanisms and their resulting
features seem absent in engineering. However, ironically, it is
in the nature of their robustness and complexity that biology
and advanced engineering are most alike. Good design in both
cases (e.g., cells and bodies, cars and airplanes) means that
users are largely unaware of hidden complexities, except through
system failures. Furthermore, the robustness and fragility
features of complex systems are both shared and necessary.
Although the need for universal principles of complexity and
corresponding mathematical tools is widely recognized, sharp
differences arise as to what is fundamental about complexity and
what mathematics is needed.

3) The differences between biology and technology (and between
organisms) are obvious, particularly at the molecular and device
level. Nevertheless, convergent evolution, a well-established
concept in both engineering and evolutionary biology, yields
remarkable similarities at higher levels of organization.
Recently, engineering systems have begun to have almost
biological levels of complexity. For example, a Boeing 777 is
fully "fly-by-wire" with 150,000 different subsystem modules,
organized via elaborate protocols into complex control systems
and networks, including roughly 1000 computers that can automate
all vehicle functions. In terms of cost and complexity, the 777
is essentially a vast control system and computer network that
just happens to fly. The consequence of good design is that its
regulatory complexity is hidden from passengers (except when
they use entertainment systems). The internal activity level is
staggering, however (e.g., the data rate recorded on the
internal state during final production testing is nearly
equivalent to one human genome every minute). Commercial
aircraft are not the only systems undergoing such explosions in
complexity as a result of advanced controls and embedded
networking; virtually all technologies are evolving similarly.
The authors suggest that this technological evolution of
complexity is convergent with that of biology.

References (abridged):

1. L. von Bertalanffy, Modern Theories of Development: An
Introduction to Theoretical Biology (Oxford Univ. Press, New
York, 1933).

2. M. A. Savageau, Biochemical Systems Theory (Addison-Wesley,
Reading, MA, 1976).

3. M. A. Savageau, Genetics 149, 1665 (1998)

4. C. V. Rao and A. P. Arkin, Annu. Rev. Biomed. Eng. 3, 391
(2001)

5. M. Dickinson, et al., Science 288, 100 (2000)

Science 2002 295:1664

ScienceWeek http://www.scienceweek.com

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

13. ON DEFECT TURBULENCE

The "Prandtl number" is a dimensionless number occurring in the
dimensional analysis of convection in a fluid due to the presence
of a hot body, the number given by Cn/Kr, where where (C) is the
heat capacity per unit volume of the fluid, (n) is the viscosity
of the fluid, (K) is the thermal conductivity of the fluid, and
(r) is the density of the fluid.

K.E. Daniels and E. Bodenschatz (Cornell University, US) discuss
defect turbulence, the authors making the following points:

1) Weakly driven, dissipative pattern-forming systems often
exhibit the spatiotemporally chaotic state of defect turbulence,
where the dynamics of a pattern is dominated by the perpetual
nucleation, motion, and annihilation of point defects (or
dislocations) [1]. Examples can be found within
striped patterns in wind driven sand, electroconvection in
liquid crystals [2], nonlinear optics [3], fluid convection
[4,5], autocatalytic chemical reactions, and Langmuir
circulation in the oceans. Researchers hope that the dynamics of
these very different systems can be characterized by a universal
description which is based only on the defect dynamics.

2) A first description of defect turbulence was given by Gil et
al (1990) for a spatiotemporally chaotic state of the complex
Ginzburg-Landau equation (CGLE). They postulated that the
nucleation rate for defect pairs is independent of the number of
pairs M, and based on the topological nature of defects the
annihilation rate is proportional to M^(2). Through detailed
balance, they showed that these assumptions lead to a squared
Poisson distribution for the probability distribution function
of M. They also found agreement with this probability
distribution function in simulations of the CGLE with periodic
boundary conditions. Rehberg et al. [2] measured probability
distribution function of M for defect turbulence in
electroconvection of nematic liquid crystals and found it to be
consistent with the predicted squared Poisson distribution.
Later, Ramazza et al [3] investigated a defect turbulent state
in optical patterns and found that their data were not
conclusive. To date, studies in both simulation and experiment
have relied purely on comparisons of the probability
distribution functions. The gain and loss rates, fundamental to
the universal description of defect turbulence, have not been
measured. In addition, effects due to boundaries have not been
considered.

3) The authors report experimental results on the defect
turbulent state of undulation chaos in inclined layer convection
of a fluid of Prandtl number of approximately 1. By tracking all
defects in a finite area of the convection cell, the authors
measured, for the first time, defect creation, annihilation,
leaving, and entering rates for a defect turbulent state. The
observed pair creation and annihilation rates agree with
predictions.

References (abridged):

I. P. Coullet, L. Gil, and J. Lega, Phys. Rev. Lett. 62, 1619
(1989).

2. I. Rehberg, S. Rasenat, and V. Steinberg, Phys. Rev. Lett.
62, 756 (1989).

3. P. Ramazza, S. Residori, G. Giacomelli, and F. Arecchi,
Europhys. Lett. 19, 475 (1992).

4. S. W. Morris, E. Bodenschatz, D. S. Cannell, and G. Ahlers,
Phys. Rev. Lett. 71, 2026 (1993).

5. A. L. Porta and C. M. Surko, Physica (Amsterdam) 139D, 177
(2000).

Phys. Rev. Lett. 2002 88:034501

ScienceWeek http://www.scienceweek.com

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

14. ON THE DEVELOPMENT OF ENZYME MIMICS

Enzymes are among the most important entities in biological
systems, with a high degree of specificity and the ability to
increase the rates of certain chemical reactions by factors of
as much as 10^(5) or 10^(6). In all cases, this action by
enzymes is apparently based on a specific site of the enzyme
polymer catalyzing an intermediate transition state in a
chemical reaction. In recent years, chemists have focused their
attention on the possibility of creating synthetic enzymes to be
used as catalysts in specific commercially important reactions.

Guenter Wulff (Heinrich-Heine University Dusseldorf, DE)
discusses enzyme mimics, the author making the following points:

1) The development of new and efficient catalysts plays a
central role in chemical research, and the progress in synthetic
work, both scientifically and technically, depends greatly on
the quality of the catalysts. In the preparation of such
catalysts, a promising approach is to translate the principles
of enzyme catalysis for the design of new catalytic materials.
Thus, artificial enzyme analogues might be synthesized that
possess a high catalytic activity and also show substrate,
reaction, and stereoselectivity comparable to biological
enzymes. At the same time, the synthetic catalysts might be more
accessible, more stable, and catalyze a larger variety of
reactions. In addition, such enzyme mimics offer the opportunity
that the characteristics of enzyme catalysis can be studied in
greater detail by systematically varying and simplifying the
functional groups in the active site, and this can help gain a
better understanding of the entire process of enzyme catalysis.

2) In recent years there has occurred remarkable progress in the
design of enzyme mimics based on low molecular weight
substances. Cram (1) and Lehn (2) made use of crown ethers or
cyptands as the molecular hosts providing cavities for specific
binding. Furthermore, it was possible to include catalytically
active functional groups within the cavity in the correct
vicinity to reacting groups of the bound substrate. Remarkable
enhancements in rate and selectivity were observed, though
turnover numbers of such reactions were mostly poor. Other hosts
have been used in the form of cyclodextrins (for reviews, see
refs 3-5), large ring systems, or in the form of certain concave
molecules for performing selective chemical operations.

3) Of special interest in preparing enzyme mimics would be the
use of synthetic polymeric substances, since these compounds are
usually very stable against heat, chemicals, and solvents, and
they can easily be fabricated in a form suitable for industrial
application. Basically, the use of polymers makes the system
more complicated compared to its low molecular weight
counterparts, since the support needs to be prepared in a
defined three-dimensional structure. On the other hand, polymers
offer certain advantages if the macromolecular nature of enzymes
is taken into consideration. In fact, many of the unique
features of enzymes are directly related to their polymeric
nature. This is particularly true for the high cooperativity of
functional groups and for dynamic effects such as induced fit,
the allosteric effect, and the steric strain exhibited by
enzymes.

References (abridged):

1. Cram, D. J. Angew. Chem. 1988, 100, 1041-1052; Angew. Chem.,
Int. Ed. Engl. 1988, 27, 1009-1020.

2. Lehn, J. M. Angew. Chem. 1988, 100, 91-106; Angew. Chem.,
Int. Ed. Engl. 1988, 27, 89-104.

3. D'Souza, V. T.; Hanabusa, K.; O'Leary, T.; Gadwood, R. C.;
Bender, M. L. Biochem. Biophys. Res. Commun. 1985, 129, 727-732.

4. Wenz, G. Angew. Chem. 1994, 106, 851-870; Angew. Chem., Int.
Ed. Engl. 1994, 33, 803-822.

5. Breslow, R. Acc. Chem. Res. 1994, 28, 146-153

Chem. Rev. 2002 102:1

ScienceWeek http://www.scienceweek.com

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

15. CURRENT-INDUCED FORCES IN MOLECULAR WIRES

In 1974, Aviram and Ratner first proposed the idea of a
molecular rectifier based on organic compounds consisting of
pi-donor and pi-acceptor moieties linked by a saturated spacer
and sandwiched between two metallic electrodes, and this concept
was experimentally verified in 1997. Measurements have also
demonstrated that small conjugated molecules, typically
phenylene-based derivatives, can behave as a conducting wire
when inserted into a metallic break junction or when anchored on
a metallic surface and contacted by a scanning tunneling
microscope tip. Such molecules with asymmetric chemical
structures are often observed to display rectifying behavior. In
addition, it has been demonstrated that a current can flow along
quantum wires made of carbon nanotubes or DNA molecules
positioned between two metallic electrodes. In parallel with
these studies, many theoretical efforts have been devoted to the
understanding of conduction mechanisms in molecular wires and
the simulation if I-V (current-voltage) characteristics of
molecular junctions. These studies have addressed the way
molecular conductance is affected by a) the electronic structure
of the molecule; b) the geometry of the metal/molecule interface
and the nature of the chemical interactions at that interface;
and c) the profile of the electrostatic potential across the
junction (which can drop abruptly at the interfaces). Molecules
sandwiched between two metallic contacts can also be used for
the fabrication of molecular resonant tunneling diodes, with I-V
characteristics displaying a low-voltage negative resistance
behavior (i.e., an initial rise in current followed by a sharp
decrease when the voltage is progressively augmented), instead
of the linear increase expected from Ohm's law or the staircase
behavior reported for molecular junctions. (V. Karzazi et al: J.
Am. Chem. Soc. 2001 123:10076)

M. Di Ventra et al (Virginia Polytechnic Institute, US) discuss
molecular wires, the authors making the following points:

1) The phenomenon of atom motion due to current flow
(electromigration) has been extensively studied in the past both
from the fundamental standpoint and for its importance in
microelectronics [1-4]. Most recently, a new electronics is
emerging that envisions the use of single molecules or molecular
wires as fundamental components in electronic devices [5]. For
instance, it has been demonstrated that molecules can operate as
Coulomb blockade structures, transistors, diodes, or switching
devices with high negative differential resistance even at room
temperature. Since electromigration has been a major concern in
conventional microelectronics due to current-induced device
breakdown, the question arises as to whether current-induced
forces may present a severe limitation to the development of
molecular electronics.

2) It was recognized in early theoretical work [1-4] that
current-induced forces on a given physical system depend
strongly on the microscopic details of the self-consistent
electric field that is created upon scattering of the electrons
across the region of interest. Self-consistency in the
calculation of the local electric field with the correct
scattering boundary conditions is thus essential to have
meaningful quantitative results on current-induced forces.

3) The authors report first-principles calculations of
current-induced forces in molecular wires for which experiments
are available. The authors investigate, as an example, the
effect of current-induced forces on a benzene molecule connected
to two bulk electrodes via sulfur end groups. The authors report
they find that the molecule twists around an axis perpendicular
to its plane and undergoes a "breathing" oscillation at resonant
tunneling via antibonding states. However, current-induced
forces do not substantially affect the absolute value of the
current for biases as high as 5 V, suggesting that molecular
wires can operate at very large electric fields without
current-induced breakdown.

References (abridged):

1. R. Landauer and J.W.F. Woo, Phys. Rev. B 10, 1266 (1974).

2. A.K. Das and R. Peierls, J. Phys. C 8, 3348 (1975).

3. L.J. Sham, Phys. Rev. B 12, 3142 (1975).

4. R. S. Sorbello, Solid State Phys., edited by H. Ehrenreich
and F. Spaepen (Academic Press, New York, 1997), Vol. 51, p.
159; and references therein.

5. See, e.g., Molecular Electronics: Science and Technology,
edited by A. Aviram and M. A. Ratner (New York Academy of
Sciences, New York, 1998).

Phys. Rev. Lett. 2002 88:046801

ScienceWeek http://www.scienceweek.com

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

16. ON MAGNETIC REFRIGERANTS

In general, the term "magnetocaloric effect" (thermomagnetic
effect) refers to a reversible change of temperature resulting
from a change in the magnetization of a ferromagnetic or
paramagnetic substance. The effect increases as the initial
temperature of the substance is lowered, so that the effect has
been used for the production of temperatures approaching
absolute zero. At very low temperatures, paramagnetic substances
become antiferromagnetic, restricting further cooling. (A
"ferromagnetic substance" is a material (e.g., iron) in which
there may be a permanent magnetic moment, and in which the spins
of the atoms are aligned parallel to each other. In general,
"paramagnetic substances" and paramagnetic chemical groups have
a capability to be magnetized which is slightly greater than
that of a vacuum and much less than that of iron. The
paramagnetism is due to the presence of permanent magnetic
dipoles caused by unpaired electron spins.)

O. Tegus et al (University of Amsterdam, NL) discuss magnetic
refrigerants, the authors making the following points:

1) Magnetic refrigeration techniques based on the magnetocaloric
effect have recently been demonstrated as a promising
alternative to conventional vapor-cycle refrigeration (1). In a
material displaying the magnetocaloric effect, the alignment of
randomly oriented magnetic moments by an external magnetic field
results in heating. This heat can then be removed from the
magnetocaloric effect material to the ambient atmosphere by heat
transfer. If the magnetic field is subsequently turned off, the
magnetic moments randomize again, which leads to cooling of the
material below the ambient temperature.

2) Magnetic refrigeration is an environmentally friendly cooling
technology. It does not use ozone-depleting chemicals (such as
chlorofluorocarbons), hazardous chemicals (such as ammonia), or
greenhouse gases (hydrochlorofluorocarbons and
hydrofluorocarbons). Another important difference between
vapor-cycle refrigerators and magnetic refrigerators is the
amount of energy loss incurred during the refrigeration cycle.
The cooling efficiency of magnetic refrigerators working with
gadolinium (Gd) has been shown4 to reach 60% of the theoretical
limit, compared to only about 40% in the best gas-compression
refrigerators. The use of magnetic refrigerators with such high
energy efficiency will result in a reduced consumption of fossil
fuels, in this way contributing to a reduced carbon dioxide
release. However, with the currently available magnetic
materials, this high efficiency is only realized in high
magnetic fields of 5 T.

3) The heating and cooling that occurs in the magnetic
refrigeration technique is proportional to the size of the
magnetic moments and to the applied magnetic field. This is why
research in magnetic refrigeration is at present almost
exclusively conducted on super-paramagnetic materials and on
rare-earth compounds (5). For room-temperature applications like
refrigerators and air-conditioners, compounds containing
manganese should be a good alternative. Manganese is a
transition metal of high abundance. Also, there exist (in
contrast to rare-earth compounds) an almost unlimited number of
manganese compounds with magnetic ordering temperatures near
room temperature. However, the magnetic moment of manganese is
generally only about half that of heavy rare-earth elements.
Enhancement of the caloric effects associated with magnetic
moment alignment may be achieved through the induction of a
first-order phase transition, which will result in much higher
efficiency of the magnetic refrigerator. In combination with
currently available permanent magnets, this should open the way
to the development of small-scale magnetic refrigerators that no
longer rely on rather costly and service-intensive
superconducting magnets. Another advantage of magnetocaloric
refrigerators is that the cooling power can be varied by scaling
from milliwatts to a few hundred watts.

References (abridged):

1. Glanz, J. Making a bigger chill with magnets. Science 279,
2045 (1998).

2. Pecharsky, V. K. & Gschneidner, K. A.Jr Giant magnetocaloric
effect in Gd5(Si2Ge2). Phys. Rev. Lett. 78, 4494-4497 (1997).

3. Gschneidner, K. A.Jr et al. Recent developments in magnetic
refrigeration. Mater. Sci. Forum 315-317, 69-76 (1999).

4. Zimm, C. et al. Description and performance of a near-room
temperature magnetic refrigerator. Adv. Cryogen. Eng. 43,
1759-1766 (1998).

5. Tishin, A. M. in Handbook of Magnetic Materials Vol. 12 (ed.
Buschow, K. H. J.) 395-524 (North Holland, Amsterdam, 1999).

Nature 2002 425:150

ScienceWeek http://www.scienceweek.com

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

17. ON NUCLEAR WARHEADS

K. O'Nions et al (Ministry of Defense, UK) discuss nuclear
warheads, the authors making the following points:

1) Although details of specific warhead designs remain
classified to prevent proliferation, the broad principles are
widely understood and recorded (2). A modern thermonuclear
warhead comprises two main elements, conventionally referred to
as the primary and secondary stages. In the primary stage,
chemical high explosive is used to compress a core containing
plutonium-239 into a state of nuclear supercriticality. The
subsequent escalating fission process results in temperatures
and pressures that allow the energy generation, or yield, to be
augmented by the fusion of a deuterium-tritium mixture _ a
process known as 'boosting'. The exploding primary stage
releases copious X-rays, which can then be used to implode a
secondary stage with immense force. It is from the fissionable
and fusionable materials which constitute the secondary that the
bulk of the overall warhead yield is derived.

2) Nuclear warheads are made from materials chosen for their
special properties. They are often complex and their fundamental
properties and ageing characteristics can be difficult to
understand. The various components are integrated into a system,
which brings into play concerns about compatibility and
corrosion. The whole must remain safe and serviceable within its
operational environment, potentially for decades.

3) The scope of the necessary scientific investigation is
immense. The ultimate questions concerning warhead safety and
reliability must now be answered without the benefit of direct
evidence from nuclear tests. It is an iterative process, the
central and pivotal feature of which is a suite of high-fidelity
numerical models run on supercomputers. A series of hydrodynamic
experiments probe the phenomenology of the primary stage, and
experiments done at very high energy densities are essential to
studies of both stages. Lasers and pulsed power machines are
able to achieve relevant densities and temperatures and also
produce the only source of data on X-radiation flows. The
experimental data are used to improve both basic theory and the
algorithms used in the computational models. The improved models
are in turn validated by experiment. Finally, the predictions of
warhead performance from these models are compared with the
historical archive of nuclear test data and variations are used
for further refinement of new models. Data from a surveillance
program, in which warheads are withdrawn from the stockpile and
subjected to forensic examination, are similarly fed into the
prediction processes.

4) The design of nuclear weapons has always been first and
foremost a theoretical undertaking, with nuclear testing used to
validate and refine the models used. As designs became more
sophisticated, and the mathematical models more complex, the
interdependence of design, underground nuclear testing and model
development became firmly established. The scientific challenge
is therefore to develop a suite of enhanced numerical models of
the warhead based on a more comprehensive understanding of the
processes taking place within it. The models must be based on a
further understanding of the properties of warhead materials
such as high explosive and plutonium, under very wide ranges of
physical conditions, and on knowledge of how these properties
change with age.

References (abridged):

2. Hansen, C. US Nuclear Weapons: The Secret History (Aerofax,
Arlington, 1998).

Nature 2002 415:853

ScienceWeek http://www.scienceweek.com

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

18. ON 3-DIMENSIONAL X-RAY STRUCTURAL MICROSCOPY

B.C. Larson et al (Oak Ridge National Laboratory, US) discuss
x-ray structural microscopy, the authors making the following
points:

1) Advanced materials and processing techniques are based
largely on the generation and control of non-homogeneous
microstructures, such as precipitates and grain boundaries.
X-ray tomography can provide three-dimensional density and
chemical distributions of such structures with submicrometer
resolution (1); structural methods exist that give submicrometer
resolution in two dimensions (2-5); and techniques are available
for obtaining grain-centroid positions and grain-average strains
in three dimensions. But non-destructive point-to-point
three-dimensional structural probes have not hitherto been
available for investigations at the critical mesoscopic length
scales (tenths to hundreds of micrometers). As a result,
investigations of three-dimensional mesoscale phenomena _ such
as grain growth, deformation, crumpling, and strain-gradient
effects _ rely increasingly on computation and modeling without
direct experimental input.

2) The authors describe a 3-dimensional X-ray microscopy
technique that uses polychromatic synchrotron X-ray microbeams
to probe local crystal structure, orientation, and strain
tensors with submicrometer spatial resolution. The authors
demonstrate the utility of this approach with
micrometer-resolution 3-dimensional measurements of grain
orientations and sizes in polycrystalline aluminum, and with
micrometer depth-resolved measurements of elastic strain tensors
in cylindrically bent silicon. The authors suggest this
technique is applicable to single-crystal, polycrystalline,
composite, and functionally graded materials.

References (abridged):

1. Wang, Y. et al. A high-throughput x-ray microtomography
system at the advanced photon source. Rev. Sci. Instrum. 72,
2062-2068 (2000).

2. Di Fonzo, S. et al. Non-destructive determination of local
strain with 100-nanometre spatial resolution. Nature 403,
638-640 (2000).

3. Bilderback, D. H., Hoffman, S. A. & Thiel, D. J. Nanometer
spatial-resolution achieved in hard x-ray-imaging and Laue
diffraction experiments. Science 263, 201-203 (1994).

4. Yun, W. et al. Nanometer focusing of hard x rays by phase
zone plates. Rev. Sci. Instrum. 70, 2238-2241 (1999).

5. Lengeler, B. et al. A microscope for hard x rays based on
parabolic compound refractive lenses. Appl. Phys. Lett. 74,
3924-3926 (1999).

Nature 2002 415:887

ScienceWeek http://www.scienceweek.com

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

19. ON DNA IN BACTERIAL BIOFILMS

Among the most complex and dynamic types of common organic
coatings are "biofilms". Such films form when microbial
organisms attach to a surface and produce a highly hydrated
framework of extracellular polymers in which the microorganisms
become embedded. These biofilms may have a sorptive capacity
similar in magnitude to many reactive mineral substrates.

Cystic fibrosis is an inherited disease of the exocrine glands,
primarily affecting the gastrointestinal tract and respiratory
systems. The "exocrine" glands are glands that secret material
via excretory ducts (e.g., mucous secreting glands).

C.B. Whitchurch et al (University of Queensland, AU) discuss
bacterial biofilms, the authors making the following points:

1) Bacterial biofilms are structured communities of cells
enclosed in a self-produced hydrated polymeric matrix adherent
to an inert or living surface (1). Formation of these sessile
communities and their inherent resistance to antibiotics and
host immune attack are at the root of many persistent and
chronic bacterial infections (1), including those caused by
Pseudomonas aeruginosa, which has been intensively studied as a
model for biofilm formation (2, 3). The matrix, which holds
bacterial biofilms together, is a complex mixture of
macromolecules including exopolysaccharides, proteins, and DNA
(4). The latter has been presumed to be derived from lysed cells
and has not been thought to represent an important component of
biofilm structure. However, it has been known for many years
that some bacteria, including P. aeruginosa, produce substantial
quantities of extracellular DNA through a mechanism that is
thought to be independent of cellular lysis and that appears to
involve the release of small vesicles from the outer membrane
(5).

2) During studies of alginate biosynthesis in P. aeruginosa, the
authors report they discovered that the majority of the
extracellular material that reacted in the carbazole
colorimetric assay was not exopolysaccharide but DNA [as
determined by its peak absorbance at 260 nm, by electrophoretic
display, and by its deoxyribonuclease (DNase) but not
ribonuclease sensitivity] and therefore hypothesized that this
DNA may play a functional role in P. aeruginosa biofilms. Using
a tube ring assay (2), the authors found that addition of DNase
I to the culture medium strongly inhibited biofilm formation,
although not bacterial growth per se.

3) The authors suggest that these and other results indicate
that extracellular DNA is required for the initial establishment
of P. aeruginosa biofilms and perhaps biofilms formed by other
bacteria that specifically release DNA. The source of this DNA
is unclear, but it is presumably derived from membrane vesicles
rather than cell lysis, since the authors observed no evidence
of the latter during biofilm formation.

4) Much of the tissue damage associated with P. aeruginosa
infections of the cystic fibrosis lung epithelia is due to
inflammatory responses of the host immune system, which may
include responses to bacterial DNA. The current treatment regime
for cystic fibrosis patients includes inhalation of nebulized
recombinant human DNase I as a therapy to reduce the viscosity
of purulent sputum. Our findings suggest that DNase I treatment
might be beneficial as an early prophylactic measure to prevent
the establishment of chronic P. aeruginosa infection of the
cystic fibrosis lung by inhibiting biofilm formation. The
authors also suggest that DNase I may be useful in preventing
bacterial biofilms in other contexts.

References (abridged):

1. J. W. Costerton, P. S. Stewart, E. P. Greenberg, Science 284,
1318 (1999)

2. G. A. O'Toole, R. Kolter, Mol. Microbiol. 30, 295 (1998)

3. P. K. Singh et al., Nature 407, 762 (2000)

4. I. W. Sutherland, Trends Microbiol. 9, 222 (2001)

5. Y. Muto and S. Goto, Microbiol. Immunol. 30, 621 (1986)

Science 2002 295:1487

ScienceWeek http://www.scienceweek.com

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

20. ON MISALLOCATION OF CREDIT IN SCIENCE

Peter A. Lawrence (MRC Laboratory of Molecular Biology, UK)
discusses allocation of credit in scienc, the author making the
following points:

1) The author argues that a common way to build rank in academic
science is to annex credit from junior colleagues. To stop this,
granting agencies should meet, agree on and publicize principles
of how the contribution and responsibility of those scientists
they support should be indicated in the list of authors of
papers. These agencies should also ensure that those they pay to
run research groups put caring for their groups first and
swanning around the world or running companies second. They, as
well as prize committees and those assessing job applicants,
must cease rewarding those who misappropriate credit. "We should
stop measuring success by where scientists publish and use
different criteria, such as whether work has turned out to be
original, illuminating and correct".

2) The 1952 Nobel prize for medicine or physiology was awarded
to Selman Waksman, primarily for the discovery of streptomycin.
Yet it was his graduate student, Albert Schatz, who discovered
the antibiotic while working alone in an isolated basement
laboratory. Waksman did not once visit this laboratory during
what Schatz described (2) as "just four months of work, day and
night". Schatz even established in court that he was the joint
discoverer of the antibiotic, yet Waksman created the myth that
he alone deserved credit, a myth widely accepted by contemporary
scientists ("the higher their status, the more likely they were
to side with Waksman...without apparently acquainting themselves
with the details of the case")(3). More recently, Nobel
committees have tried hard to look beyond rank and publications
to assign credit properly. A good example is the 1984 Nobel
prize awarded to Georges K”hler and C‚sar Milstein for their
collaborative discovery of monoclonal antibodies _ K”hler was a
postdoc at the time. Unfortunately, many other prize giving
bodies do not take the same care.

3) The scientific community supports the natural tendency of the
experienced to take advantage of the inexperienced, and helps to
ensure that credit always flows up the ladder of rank. Most of
us know examples of how, over time, the contributions of younger
colleagues have become extinguished. There are some celebrated
cases [for example, Hilde Mangold (5) and Candace Pert (6)] and
countless uncelebrated ones. Although it is usually true that
some credit properly belongs to others who were not present at
the moment of discovery, it is too often the senior absentees
who manage to claim all of it.

4) The etiquette of conference lectures is revealing. A talk
summarizing the work of a group is usually given by the
principal investigator, who mentions results simply as found "in
the lab". The truth would be more like: "done by someone in my
group, I may or may not have suggested it _ in any case I would
like you, the audience, to take it as mine". At the end of the
talk, the principal investigator thanks many people, often from
over several years. The motivation may be honest, but the effect
is that nobody remembers any name except that of the speaker.

5) The exponential rise in the secondary literature allows
principal investigators to write numerous reviews of their
field, giving their own perspective of discoveries and keeping
their names in the limelight. Because journals usually limit the
number of citations in primary and secondary articles, authors
have to refer to other reviews, reinforcing a few "star" names,
fixing them in the memory and cementing them as "the" leading
experts. Principal investigators can even leave much of the
actual writing to their juniors, co-authoring reviews to ensure
that the credit goes to them.

References (abridged):

2. Schatz, A. Pak. Dent. Rev. 15, 125-134 (1965)

3. Wainwright, M. Hist. Phil. Life Sci. 13, 97-124 (1991)

4. Crewdson, J. Chicago Tribune (19 November 1989).

5. Faessler, P. E. & Sander, K. Roux's Arch. Dev. Biol. 205,
323-332 (1996)

6. Marx, J. L. Science 203, 341 (1979)

Nature 2002 415:835

ScienceWeek http://www.scienceweek.com

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

21. ON HYBRIDIZATION AND EXTINCTION

Donald A. Levin (University of Texas Austin, US) discusses
hybridization, the author making the following points:

1) The well-defined sets of attributes one finds populating the
natural world make up the fundamental units of biodiversity:
species. Investigators have now described nearly two million
species (millions more await attention) and placed them within
an elaborate taxonomic hierarchy. But even the naturalists of
antiquity realized that some organisms resemble one another so
much that they ought to be classified in the same general group
or genus. Only much later did Charles Darwin and Alfred Russell
Wallace realize that species within the same genus share many
traits because they evolved from a common ancestor. That is,
what was once one type of plant or animal split into two or more
species.

2) Despite their overall similarity, different species in the
same genera do not normally interbreed. They may be prevented
from doing so because they have widely separated home ranges or
different reproductive seasons. Indeed, that they do not freely
exchange genes, for whatever reason, defines them as separate
species. Yet in some circumstances separate species will mate,
and if such a liaison is successful, a hybrid results. Although
such hybridization never takes place in the vast majority of
genera, it is quite common in some. Botanists believe that
hybridization between species happens in 6 to 16 percent of
plant genera. Crossing between species is less common in
animals, although it is not infrequent in some groups. For
example, 9 percent of all bird species hybridize. Such a
blurring of taxonomic lines also takes place within primate
genera, including lemurs, gibbons and baboons. Anthropologists
have even speculated that humans and Neanderthals may have once
interbred.

3) With hybridization so rampant, one wonders how species ever
maintain their distinctness. They do, in part, because the
production of hybrids does not necessarily shift genetic
material between species. For genes to traffic in this way,
hybrids must cross with at least one of the parent species. In
many instances that just doesn't happen. Why? As Darwin had
observed, most hybrids are inferior to their parents. Some abort
as embryos, others die as juveniles, and others still grow to
adulthood but cannot reproduce. Mules, for example, are vigorous
but sterile: If you want to produce a mule, as people have been
doing for more than 2,000 years, you have to mate a female horse
and a male donkey. Getting it backward will result in a hinny,
which is also sterile but less robust. Hence many hybrids are
unable to pass their genes back to members of their parent
species (1-5).

References (abridged):

1. Anderson, E. 1949. Introgressive Hybridization. New York:
John Wiley & Sons.

2. Arnold, M. 1997. Natural Hybridization and Evolution. New
York: Oxford University Press.

3. Ellstrand, N. C, H. C. Prentice and }. F. Hancock. 1999. Gene
flow and introgression from domesticated plants into their wild
relatives. Annual Review of Ecology and Systematics 30:539-563.

4. Ellstrand, N. C., R. Whitkus and L. H. Rieseberg. 1996.
Distribution of spontaneous plant hybrids. Proceeding of the
National Academy of Sciences of the USA. 93:5090-5093.

5. Grant, P. R., and B. R. Grant. 1992. Hybridization of bird
species. Science 258:193-197.

American Scientist 2002 90:254

ScienceWeek http://www.scienceweek.com

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

22. ASPECTS OF NUCLEAR RADIATION TERRORISM

F.A. Mettler et al (University of New Mexico, US) discuss
nuclear terrorism, the authors making the following points:

1) To date, the assumption is that terrorists would use only one
type of agent at a time. A combination of agents could be used,
but there is not likely to be synergism between radiation and
other agents. Most chemical agents have immediate effects that
would need to be managed before the subsequent effects of
radiation could be addressed. Exposure to radiation from sources
other than a nuclear weapon should be relatively manageable,
since it is very difficult to expose many people to large doses
of radiation and small doses do not affect health for many years.

2) The use of explosives to disperse radioactive substances is
of greater concern, because explosives would spread the
substances to large numbers of people and because there might be
associated traumatic injuries. The purpose of including
radioactive material with the explosives would be to cause
additional fear and panic. The radioactive material would
probably be in solid or powdered form. The extent of its
dispersion would depend on the physical form of the source, the
explosives, and the atmospheric conditions. A major health
hazard would probably be restricted to an area of a few city
blocks. The goal of the response would be to monitor and control
the contaminated area.

3) The possibility of terrorist attacks on nuclear power plants
has been mentioned in the media. At all commercial nuclear power
plants in the US, the reactor core is encased in a thick
stainless-steel vessel within a concrete containment building.
If an accident occurs, the reactor is designed to slow down and
stop the reaction. The coolant system of a reactor does contain
some radioactivity, which could be released if the coolant
system were damaged. Released substances would probably include
radioactive iodine and noble gases. An atmospheric plume of
radioactive substances released through a breach in the reactor
core could have immediate health effects nearby. Moreover, the
release of large amounts of radioactive iodine could have
long-term effects (e.g., thyroid cancer in children) at great
distances. Many nuclear-engineering departments in universities
have small experimental reactors in densely populated urban
areas, with minimal security. These reactors contain much
smaller amounts of radioactive material, but they may be
inviting targets for terrorist attacks. In addition, "spent" but
still radioactive fuel rods are often stored in less secure
facilities. It would be very difficult, however, to expose a
large population to radiation from these solid sources.

4) A nuclear weapon requires more technical expertise and more
money to develop and use than does either a biologic or a
chemical weapon, and the use of a nuclear weapon by terrorists
is therefore considered to be less likely. Nevertheless, it is
possible to construct a low-yield (<10 kiloton) nuclear device.
A stolen compact nuclear weapon could have a higher yield. For
reference, the bomb used at Hiroshima had an approximate yield
of 13 kilotons. However, even a nuclear-weapon detonation that
fizzled could have a substantial explosive impact, even though
the yield might only be on the order of 0.01 kilotons. The
destructive effects of nuclear weapons are due to the air blast
as well as to thermal radiation. An increase in pressure of 1
psi will break glass. At 12 psi, the predicted fatality rate
among persons close to windows is 50 percent. The fireball will
cause flash and flame burns as well as burns in an ensuing
firestorm. Looking at the fireball even from several miles away
can cause temporary or permanent blindness. Ionizing radiation
is released as an intense pulse during the first minute (initial
radiation) and as fission and activation products after the
first minute (residual radiation). A ground burst injects a
large amount of radioactive soil and other materials into the
atmosphere, causing radioactive fallout that may extend over an
area of hundreds of miles. Unless persons are protected from
exposure in a shelter or are evacuated, the fallout can be
lethal at greater ranges than either the blast or the fireball
(1-5).

References (abridged):

1. Gusev I, Guskova AK, Mettler FA Jr, eds. Medical management
of radiation accidents. 2nd ed. Boca Raton, Fla.: CRC Press,
2001.

2. Management of terrorist events involving radioactive
material. NCRP report no. 138. Bethesda, Md.: National Council
on Radiation Protection and Measurements, 2001.

3, Jarrett D, ed. Medical management of radiation casualties:
handbook. AFRRI special publication 99-2. Bethesda, Md.: Armed
Forces Radiobiology Research Institute, 1999. (Also available at
http://www.afrri.usuhs.mil)

4. Committee on Radiation Battlefield Criteria, Institute of
Medicine, National Research Council. Potential radiation
exposure in military operations: protecting the soldier before,
during and after. Washington, D.C.: National Academy Press, 1999.

5. The radiological accident in Goiana. Vienna, Austria:
International Atomic Energy Agency, 1988.

New Engl. J. Med. 2002 346:1554

ScienceWeek http://www.scienceweek.com

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

23. ON GLOBAL CLIMATE CHANGE AND HEALTH

J.A. Patz and M. Khaliq (Johns Hopkins University, US) discuss
global climate change, the authors making the following points:

1) Global climate change is expected to have broad health
impacts.[1] If current warming trends continue, heat waves,
floods, and droughts and their attendant physical effects are
likely to become more frequent and severe. Warmer air
temperatures can influence the concentration of regional air
pollutants and aeroallergens. Less direct health impacts may
result from the disruption of ecosystems and of water and food
supplies, which in turn could affect infectious disease
incidence and nutritional status. Finally, sea-level rise could
lead to major population displacement and economic disruption.

2) Human activities related primarily to the burning of fossil
fuels and changes in land cover such as deforestation are
changing the concentration of atmospheric constituents or
properties of the earth's surface that help to absorb or scatter
radiant energy.[2] Since the preindustrial mid-1800s, increases
in concentrations of three major greenhouse gases, carbon
dioxide, methane, and nitrous oxide, have exceeded past changes
that occurred over the last 10 000 years; carbon dioxide alone
has increased by 30% since the late 1800s.[1] Warmer air, such
as that resulting from the greenhouse effect, can hold more
moisture and more quickly evaporate surface water, thereby
increasing the frequency of severe storms, floods, and
droughts.[1]

3) According to the United Nations Intergovernmental Panel on
Climate Change (IPCC), "An increasing body of observations gives
a collective picture of a warming world and other changes in the
climate system.[3] During the 20th century, global average
surface temperature increased about 0.6 degrees C, global
average sea level rose 10 cm to 20 cm, and snow and ice cover
decreased.[2] The latest IPCC report predicts that if current
trends continue, sea level rise will rise 45 cm and global
temperatures will increase by 3 degrees C by the year 2100.[3]

4) Small changes in global mean temperatures can produce
relatively large changes in the frequency of extreme
temperatures.[2] Mortality rates increase at both hot and cold
extremes of temperature.[4] Increases in temperature have a
direct and substantial impact on excess mortality for elderly
individuals and individuals with pre-existing illnesses. Much of
the mortality attributable to heat waves is a result of
cardiovascular, cerebrovascular, and respiratory disease.[5] A
1995 heat wave in Chicago that caused 514 heat-related deaths
(12 per 100 000 population) may be part of a recent trend of
longer, more frequent heat waves and record-setting
temperatures. Long-term global warming trends are further
exacerbated by the "heat island" effect, whereby high
concentrations of heat-retaining surfaces such as asphalt and
tar roofs sustain higher temperatures through the night. Heat
waves also have the secondary effect of worsening urban air
pollution. Ozone, which forms chemically from precursor
pollutants, is the most temperature-dependent air pollutant and
may contribute to the development of asthma in children.

References (abridged):

1. Patz JA, Engelberg D, Last J. The effects of changing weather
on public health. Ann Rev Public Health. 2000;21:271-307.

2. Intergovernmental Panel on Climate Change (IPCC). Climate
Change 2001: The Scientific Basis: Contribution of Working Group
I to the Third Assessment Report of the IPCC. Houghton J, Ding
Y, Griggs M, et al, eds. Cambridge, England: Cambridge
University Press; 2001.

3. McMichael A. Human health. In: IPCC Working Group II, ed.
Climate Change 2001: Impacts, Adaptation, and Vulnerability.
Cambridge, England: Cambridge University Press; 2001:453-485.

4. Curriero FC, Heiner KS, Samet JM, et al. Temperature and
mortality in 11 cities of the eastern United States. Am J
Epidemiol. 2002;155:80-87.

5. Kilbourne E. Heat waves. In: Noji E, ed. The Public Health
Consequences of Disasters. New York, NY: Oxford University
Press; 1997:51-61.

J. Am. Med. Assoc. 2002 287:2283

ScienceWeek http://www.scienceweek.com

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

24. ASSOCIATION BETWEEN DURATION OF BREASTFEEDING AND ADULT
INTELLIGENCE

E.L. Mortensen et al (Copenhagen University Hospital, DK)
discuss the association between breastfeeding and adult
intelligence, the authors making the following points:

1) A number of studies have suggested a positive association
between breastfeeding and cognitive and intellectual development
in early and middle childhood.(1, 2) However, studies of
correlations between childhood and adult intelligence show that
intelligence is quite unstable during the first decade of life,
particularly in early childhood.(3) Consequently, it is possible
that exclusively or predominantly bottlefed children may catch
up and ultimately achieve the same intelligence level as
children who were breastfed.

2) Few studies have examined the relationship between
breastfeeding and intellectual development in older children and
adolescents. One study observed significantly higher scores in
breastfed children at 15 years of age on tests of nonverbal
ability, mathematics, and reading ability,(4) and another study
demonstrated a positive association between breastfeeding and
high school attainment at 18 years of age.(5) The latter study
also demonstrated an apparent dose-response relationship between
duration of breastfeeding and scores on intelligence tests (at
ages 8 and 9 years) and on standardized tests of reading and
mathematics (at ages 8, 10, 12, and 13 years). These studies --
and most others assessing cognitive ability in childhood --
included a number of demographic, family, and perinatal factors
as covariates. Despite the fact that controlling for these
factors generally resulted in diminution of the effect, the
positive association of breastfeeding with various measures of
cognitive function remained significant and thus appeared robust.

3) In an effort to overcome difficulties of interpreting
previous studies, the authors describe the association between
duration of breastfeeding and adult intelligence, applying 2
different intelligence measures, in 2 nonoverlapping samples
from a perinatal cohort with a wide range of potentially
confounding variables collected prospectively. In both samples,
intelligence was assessed in young adulthood, an age when
cognitive functioning is optimal and intelligence test scores
are highly stable. From their results, the authors conclude:
Independent of a wide range of possible confounding factors, a
significant positive association between duration of
breastfeeding and intelligence was observed in 2 independent
samples of young adults, assessed with 2 different intelligence
tests.

References (abridged):

1. Anderson JW, Johnstone BM, Remley DT. Breast-feeding and
cognitive development: a meta-analysis. Am J Clin Nutr.
1999;70:525-535.

2. Golding J, Rogers IS, Emmett PM. Association between
breastfeeding, child development and behaviour. Early Hum Dev.
1997;49 Suppl:S175-184.

3. Schuerger JM, Witt AC. The temporal stability of individually
tested intelligence. J Clin Psychol. 1989;45:294-302.

4. Rodgers B. Feeding in infancy and later ability and
attainment: a longitudinal study. Develop Med Child Neurol.
1978;20:421-426.

5. Horwood LJ, Fergusson DM. Breastfeeding and later cognitive
and academic outcomes. Pediatrics. 1998;101:1-7.

J. Am. Med. Assoc. 2002 287:2365

ScienceWeek http://www.scienceweek.com

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

25. IN FOCUS: ON BECQUEREL'S DISCOVERY

"In 1912, the eminent British scientist Ernest Rutherford
(1871-1937) succeeded for the first time in obtaining convincing
evidence that atomic nuclei really exist. However, the history
of our knowledge concerning atomic nuclei begins earlier. The
nuclear chronicle should actually begin with 1896. This starting
point was marked by a scientific error, or, to be more precise,
by an incorrect scientific hypothesis.

"The question at hand concerned the nature of the then
mysterious X-rays discovered just before (1895) by the German
scientist Wilhelm Roentgen (1845-1923). Men of science in all
countries were then under the impression of this discovery.
Roentgen's work was subjected to careful study and discussion.
The French scientist Henri Becquerel (1852-1908) took note of
Roentgen's remark that the invisible X-rays he had discovered
emerge from the end of a glass tube that glows with a yellowish
green light which resembles the light of fluorescent substances.
Both the yellowish green glow and the X-rays come out of the
same spot of the glass tube. This was not fortuitous. In the
tube with which Roentgen performed his investigations, the
production of X-rays was always accompanied by a yellowish green
illumination of the glass.

"Becquerel had spent a long time in the study of various
fluorescent materials which under the action of sunlight begin
to radiate their own peculiar light. The idea that stimulated
Becquerel's experiments was simple: is not fluorescence the
cause of X-rays? Maybe X-rays exist whenever there is
fluorescence? Now, in the light ot our knowledge concerning the
constitution of the atom and the nature of X-rays, this idea
seems absurd, but at that time, when the nature of these rays
was unknown, this assumption appeared quite natural.

"Becquerel was, of course, just lucky. It was by sheer accident
that for the fluorescent material he took one of the uranium
salts, the double sulfate of uranium and potassium. This
circumstance predetermined the success of the experiment which
was extremely simple and amounted to the following:

"A photographic plate was carefully wrapped in black paper that
did not pass visible rays. Then the uranium potassium sulfate
was placed on the paper. The plate was then placed in bright
sunlight. Several hours later it was developed with all possible
precaution. A dark spot was detected on the plate and in form
resembled the silhouette of the fluorescent material. Becquerel
performed a series of control experiments and showed that this
darkening arose from the action on the photographic plate of
rays coming from the uranium crystals and passing through the
black paper that is impenetrable to the sun's light.

"At first Becquerel did not doubt that these were the X-rays.
But he soon saw that he was mistaken. During these experiments,
one of the days happened to be overcast and the uranium salt was
hardly at all fluorescent. Assuming the experiment to be
unsuccessful, he put the plate with the uranium salt back into
the drawer of the case where it remained several days. Before
his next experiment he developed this plate, since he was not
sure that it was good any longer. To his surprise he saw a dark
spot on the plate that was the image of the salt; the intensity
of this image was exceptionally great. But in the dark case the
salt had not fluoresced. Hence, fluorescence had nothing to do
with it: there was something that affected the plate without
fluorescence.

"It was obvious that Becquerel had encountered some kind of new
rays, and very soon it was established that these rays were due
to uranium. Only such fluorescent materials as contained uranium
affected a photographic plate, and a plate was affected by any
of the uranium salts. But the strongest action was that produced
by uranium itself.

"The rays discovered by Becquerel resemble to some extent
Roentgen's rays. They act on a photographic plate, and pass
through black paper and thin layers of metal. However, these
rays differ greatly. X-rays arise during an electric discharge
in a highly rarefied gas. The pressure of the gas must be of the
order of a millionth part of atmospheric pressure. A very high
voltage (hundreds of times greater than the 110 volts that we
are accustomed to in everyday life) must be applied to the
electrodes before a discharge takes place. In these conditions,
the X-rays are produced regardless of the nature ot the gas in
the X-ray tube and also of the substance of the electrodes.

"Becquerel's rays do not require any electric potential, either
large or small. And no rarefied gas is necessary. X-rays appear
only in the presence of an electric discharge, while Becquerel's
rays radiate continuously and at all times."

M. Korsunsky: The Atomic Nucleus. Moscow, 1958, p.7. Translated
from the Russian by G. Yankovsky.

ScienceWeek http://www.scienceweek.com

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

NOTICES

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

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

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

CHANGE OF EMAIL ADDRESS:

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

SCIENCE-WEEK SUBSCRIPTIONS:

The amount of payment for ScienceWeek subscriptions is
voluntary. Further information concerning subscriptions is
available at: http://www.scienceweek.com/subinfo.htm

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

Editor/Publisher: Dan Agin

Managing Editor: Claire Haller

Associate Editor: Joan Oliner

Copyright (c) 1997-2002 SCIENCE-WEEK

All Rights Reserved

US Library of Congress ISSN 1529-1472

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

ScienceWeek/Spectrum Press Inc.

3023 N. Clark Street #109

Chicago, 60657-5205 IL, USA.

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

-----end file