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ScienceWeek
SCIENCE-WEEK - March 15, 2002 - Vol. 6 Number 11
An Email Research Digest Published Weekly Since 1997
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Humanity is far from perfect in its understanding,
abilities, or intentions. We must not imagine, however,
that we and our civilization are less than precious.
We have the gift of intelligence, and that is the
finest thing this planet has ever produced.
-- Michael A. Seeds
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Section 1
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Contents of this Issue (Full reports in Section 2):
[(*) = includes background reports]
Basic Sciences
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1. Bose-Einstein Condensate in a Surface Microtrap
2. Antarctic Oscillations at the Oligocene/Miocene Boundary
3. Pressure Effects on Hydrophobic Interactions (*)
4. On the Rational Synthesis of Fullerenes
5. Bell's Theorem and Hidden Variables in Quantum Mechanics (*)
6. On Edward U. Condon (1902-1974)
7. Accelerated Gray Matter Loss in Early-Onset Schizophrenia (*)
8. Multiple Sclerosis
9. The Nuclear Envelope
10. On Chromatin
11. Genes, Differentiation, and Development
12. On Simulations of Biomolecular Processes
Praxis
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13. On Nanowire Building Blocks
14. Solar Energy and Inorganic Photochemistry
15. Controlling the Shape of Nanoparticles
16. New Carriers of Sensitizers in Photodynamic Therapy
17. Incorporation of Quantum Dots in Colloids
18. Nanoparticle Systems and Research
19. Conflicts of Interest in Basic Scientific Research
20. Malignant Melanoma: An Update (*)
21. On Quarantine Following Bioterrorism in the US
22. Adaptation of Crops to Arid Conditions
23. Genomics and Neurology
24. On the Global Diabetes Epidemic
Miscellany
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25. In Focus: On Bacterial Plasmids
26. From the SW Archive: 1932 -- The Year of Physics
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Section 2
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1. BOSE-EINSTEIN CONDENSATE IN A SURFACE MICROTRAP
According to current physics, all particles in nature are
either fermions or bosons, with fermions (always elementary
particles) having half-integer spin (spin-states characterized by
half-integer multiples of Planck's constant divided by 2ã), and
bosons (all other particles) having integer spin (spin-states
characterized by integer multiples of Planck's constant divided
by 2ã). In general, bosons are particles that obey Bose-Einstein
statistics, and they include photons, pi mesons, all nuclei
having an even number of particles, and all particles with
integer or zero spin. Pi mesons (pions) are subatomic particles
with masses approximately 270 times the mass of the electron.
Bose-Einstein statistics is the statistical mechanics of a
system of indistinguishable particles for which there is no
restriction on the number of particles that may simultaneously
exist in the same quantum energy state. Particles that obey
Bose-Einstein statistics are called "bosons".
In general, "Bose-Einstein condensation" is a phenomenon
occurring in a macroscopic system consisting of a relatively
large number of bosons at a sufficiently low temperature
(microkelvins down to nanokelvins) in which a significant
fraction of the particles occupy a single quantum state of lowest
energy (the ground state). In an atomic Bose-Einstein condensate,
several thousand atoms essentially become a single atom, a
"superatom", and this effect has been observed experimentally
with atoms of rubidium and lithium, the atoms trapped and cooled
by special methods.
So-called "matter waves" are de Broglie waves, a set of
waves that represent the behavior, under appropriate conditions,
of a particle (for example, the diffraction of the particle by a
crystal lattice). The wavelength is the de Broglie wavelength and
is given by the de Broglie equation L = h/mv, where (L) is the
wavelength, (h) is Planck's constant, (m) is the mass and (v) the
velocity of the particle.
... ... H. Ott et al (University of Tuebingen, DE) discuss Bose-
Einstein condensates, the authors making the following points:
1) Trapped ultracold atoms are fascinating model systems for
studying quantum statistical many-particle phenomena. Confined in
optical or magnetic trapping potentials, the atomic gas reaches
quantum degeneracy at ultra-low temperatures (typically less than
1 microkelvin) and very small densities (approximately 10^(14)
atoms per cubic centimeter). In this regime, the interaction
between the atoms is still weak and the system is accessible to
precise theoretical description.
2) One of the most intriguing properties of such ultracold
atomic ensembles is the formation of macroscopic matter waves
with extraordinarily large coherence lengths. For single thermal
atoms, the coherence length is determined by the thermal de
Broglie wavelength and is thus limited to the micron range, even
for temperatures as small as 1 microkelvin. In contrast, a Bose-
Einstein condensate may show coherence effects over a much larger
distance. It is therefore of interest to combine degenerate
quantum gases with magnetic micropotentials, which may allow for
coherent atomic optics on the surface of a microstructured "atom
chip". But from an experimental standpoint, it is unclear how a
degenerate Bose gas behaves in a waveguide structure, where it
acquires a quasi-one-dimensional character.
3) The authors report they have experimentally generated a
Bose-Einstein condensate in a microstructured magnetic surface
trap, the setup allowing for investigation of coherence phenomena
of degenerate quantum gases in extremely anisotropic magnetic
waveguides.
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Phys. Rev. Lett. 2001 87:230401
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ScienceWeek 15 Mar 2002 www.scienceweek.com
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2. ANTARCTIC OSCILLATIONS AT THE OLIGOCENE/MIOCENE BOUNDARY
T.R. Naish et al (Institute of Geological and Nuclear Sciences,
NZ) discuss the East Antarctic ice sheet, the authors making the
following points:
1) Between 34 million years ago and 15 million years ago,
when planetary temperatures were 3 to 4 degrees C. warmer than at
present, and atmospheric carbon dioxide concentrations were twice
as high as today, the Antarctic ice sheets may have been
unstable. Oxygen isotope records from deep-sea sediment cores
suggest that during this time fluctuations in global temperatures
and high-latitude continental ice volumes were influenced by
Earth's orbital cycles. But it has hitherto not been possible to
calibrate the inferred changes in ice volume with direct evidence
for oscillations of the Antarctic ice sheets.
2) The authors present sediment data from shallow marine
cores in the western Ross sea that exhibit well-dated cyclic
variations, and which link the extent of the East Antarctic ice
sheet directly to orbital cycles during the Oligocene/Miocene
transition (24.1 to 23.7 million years ago). Three rapidly
deposited glacimarine sequences are constrained to a period of
less than 450,000 years by the age model of the authors,
suggesting that orbital influences at the frequencies of
obliquities (40,000 years) and eccentricity (125,000 years)
controlled the oscillations of the ice margin at that time. An
erosional hiatus covering 250,000 years provides direct evidence
for a major episode of global cooling and ice-sheet expansion
approximately 23.7 million years ago, which had previously been
inferred from oxygen isotope data.
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Nature 2001 413:719
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3. PRESSURE EFFECTS ON HYDROPHOBIC INTERACTIONS
T. Ghosh et al (Rensselaer Polytechnic Institute, US) discuss
hydrophobic interactions, the authors making the following
points:
1) Pressure effects in proteins and on physicochemical
interactions underlying protein stability have attracted
considerable attention in recent years. Experimental and
theoretical studies have focused on the structural,
thermodynamic, and kinetic aspects of unfolding of proteins upon
application of high hydrostatic pressures. Motivation for these
studies is derived in part from their direct relevance to many
important applications.
2) Pressures of the order of 2000 atmospheres have been
demonstrated to be able to dissociate biomolecular complexes such
as antigen-antibody complexes or protein aggregates. Indeed,
recent studies demonstrate that pressure can provide an effective
yet mild means of recovering proteins bound to biospecific
adsorbents, as well as for separation of proteins in inclusion
bodies formed during their overexpression.
3) From a fundamental perspective, an understanding of
pressure unfolding of proteins in general, and of its
thermodynamics in particular, presents a significant challenge
brought to light by Kauzman more than a decade ago. Kauzman
pointed out that modeling protein unfolding by the commonly used
"hydrophobic transfer" model fails almost completely to explain
pressure denaturation of proteins. In particular, the volume
change upon protein unfolding is found to be positive at low
pressures but negative at pressures above 1000 to 2000
atmospheres, whereas the corresponding volume changes observed
for the transfer of hydrocarbon into water display opposite
behavior.
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J. Am. Chem. Soc. 2001 123:10997
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Related Background:
PRESSURE DEPENDENCE OF HYDROPHOBIC INTERACTIONS OF PROTEINS
The term "denaturation of proteins" refers to an alteration of
protein folding structure by heat, acid, alkali, mechanical
shaking, etc., the result a change in physical properties such as
solubility. "Hydrophobic aggregates" are aggregates of nonpolar
moieties, the aggregation often resulting from Van der Waals
interactions (i.e., dispersion interactions), and in the case of
many proteins, such aggregates of hydrophobic protein side chains
play an important role in producing particular folding
conformations. Clathrates are molecular compounds formed by the
inclusion of molecules of one type in holes in the lattice of
another type, and clathrate hydrates are clathrates involving
significant hydration as a component of the inclusion compound.
... ... Hummer et al (5 authors at 3 installations, US) report a
model explaining pressure denaturation of proteins by the
pressure destabilization of hydrophobic aggregates, the model
using information theory of hydrophobic interactions, with
clathrate hydrates predicted to form by virtually the same
mechanism that drives pressure denaturation of proteins. The
authors suggest that studies of changes in protein conformation
with pressure will not only elucidate the fundamentals of
conformation thermodynamics, but will also clarify adaptation
processes of barophilic organisms such as those living under
extreme pressures in the deep sea.
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Proc. Nat. Acad. Sci. 1998 17 Feb
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Related Background:
SURFACE TOPOGRAPHY AND HYDROPHOBIC HYDRATION OF BIOMOLECULES
Cheng and Rossky (University of Texas Austin, US) present
computer simulations of the interactions between the polypeptide
mellitin and water. Many biomolecules are characterized by
surfaces containing extended nonpolar regions, and the
aggregation and removal of such surfaces from water is believed
to play a critical role in the biomolecular assembly in cells. A
better understanding of the hydrophobic hydration of biomolecules
may therefore yield new insights into intracellular assembly.
Conventional views hold that the hydration shell of small
hydrophobic solutes is clathrate-like, characterized by local
cage-like hydrogen-bonding structures and a distinct loss in
entropy. The hydration of extended nonpolar planar surfaces,
however, appears to involve structures that are orientationally
inverted relative to clathrate-like hydration shells, with
unsatisfied hydrogen bonds directed toward the hydrophobic
surface. The authors suggest their computer simulations
demonstrate that the two different hydration structures also
exist near a biomolecular surface, and that the two structures
are distinguished by a substantial difference in water-water
interaction enthalpy. The authors further suggest that the strong
influence of surface topography on the structure and free energy
of hydrophobic hydration is likely to hold in general, and will
be particularly important for the many biomolecules whose
surfaces contain convex patches, deep or shallow concave grooves,
and roughly planar areas.
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Nature 1998 392:696
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4. ON THE RATIONAL SYNTHESIS OF FULLERENES
M.M. Boorum et al (Boston College, US) discuss the synthesis of
fullerenes, the authors making the following points:
1) Despite more than a decade of intensive research on
fullerenes, chemists worldwide still have no general methods or
strategies available for the rational synthesis of these
polyhedral carbon allotropes as discrete and preselected targets.
Under carefully controlled conditions, the vaporization of
graphite generates substantial amounts of C(sub60) and C(sub70),
but this complicated process remains poorly understood and is
intolerant to alteration. Higher fullerenes can be obtained from
this source only in minuscule amounts through tedious
chromatographic separations and likely will never be available in
quantity except by rational synthesis.
2) Before we can hope to develop rational syntheses of
individual higher fullerenes, the goal of synthesizing C(sub60)
by rational methods must first be met. In this connection,
several research groups have prepared macrocyclic polyalkynes
that shed multiple appendages when subjected to laser
desorption/ionization, and the high-energy intermediates thus
generated collapse to C(sub60) in a mass spectrometer. The
considerable ambiguity about which atoms in these molecular
precursors become bonded to which other atoms as the fullerene
takes shape, however, precludes characterization of these
processes as entirely "rational" syntheses.
3) The authors report the synthesis of a stable polycyclic
aromatic hydrocarbon, C(sub60)H(sub30), that incorporates all 60
of the carbon atoms and 75 of the 90 carbon-carbon bonds required
to form C(sub60), and its laser-induced cyclodehydrogenation to
C(sub60). Control experiments verify that the C(sub60) is formed
by a molecular transformation directly from the C(sub60)H(sub90)
polycyclic aromatic hydrocarbon and not by fragmentation and
recombination in the gas phase.
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Science 2001 294:828
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5. ON BELL'S THEOREM AND HIDDEN VARIABLES IN QUANTUM MECHANICS
A "hidden variables theory" is one of a class of physical
theories which deny that the quantum state of a physical system
is a complete specification. The hidden variables are those
components of the hypothetical complete state that are not
contained in the quantum state.
"Bell's inequality", formulated by John Bell (1928-1990) in
1964, is one of a family of inequalities concerning the
probabilities of joint occurrence of certain events in two well-
separated parts of a composite system, the inequality implied by
any hidden variables theory that satisfies an appropriate
locality condition. In this context, in general, a locality
condition is a condition such that no interaction between two
entities can occur in less time than the time required for light
to travel from one entity to the other. For example, any apparent
instantaneous effect of one entity upon the other entity implies
locality is not obeyed.
"Bell's theorem" is the theorem that no hidden variables
theory satisfying an appropriate locality condition can make
statistical predictions in complete agreement with those of
quantum mechanics. In other words, there are situations in which
quantum mechanics predicts a violation of Bell's inequality.
Another formulation is that any hidden variables theory that
forbids instantaneous interactions cannot make predictions in
complete agreement with those of quantum mechanics.
... ... K. Hess and W. Philipp (University of Illinois, US)
discuss Bell's theorem, the authors making the following points:
1) Einstein, Podolsky, and Rosen (EPR) (1935) designed a
gedanken experiment that suggested a theory that was more
complete than quantum mechanics. The EPR design was later
realized in various forms, with experimental results close to the
quantum mechanical prediction. The experimental results by
themselves have no bearing on the EPR claim that quantum
mechanics must be incomplete nor on the existence of hidden
parameters. However, the well known inequalities of Bell are
based on the assumption that local hidden parameters exist, and
when combined with conflicting experimental results, do appear to
prove that local hidden parameters cannot exist. This fact leaves
only instantaneous actions at a distance (called "spooky" by
Einstein) to explain the experiments.
2) The Bell inequalities are based on a mathematical model
of the EPR experiments. They have no experimental confirmation,
because they contradict the results of all EPR experiments. In
addition to the assumption that hidden parameters exist, Bell
tacitly makes a variety of other assumptions. For example, Bell
assumes that the hidden parameters are governed by a single
probability measure independent of the analyzer settings.
3) The authors argue that the mathematical model of Bell
excludes a large set of local hidden variables and a large
variety of probability densities. The authors' set of local
hidden variables includes time-like correlated parameters and a
generalized probability density. The authors state they prove
that their extended space of local hidden variables does permit
derivation of the quantum result and is consistent with all known
experiments.
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Proc. Nat. Acad. Sci. 2001 98:14224,14228
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Related Background:
IN FOCUS: ON QUANTUM MECHANICS, REALITY, AND HIDDEN VARIABLES
"The formalism of the quantum theory leads to results that agree
with experiment with great accuracy and covers an extremely wide
range of phenomena. As yet there are no experimental indications
of any domain in which it might break down. Nevertheless, there
still remain a number of basic questions concerning its
fundamental significance which are obscure and confused... All
that is clear about the quantum theory is that it contains an
algorithm for computing the probabilities of experimental
results. But it gives no physical account of individual quantum
processes. Indeed, without the measuring instruments in which the
predicted results appear, the equations of the quantum theory
would be just pure mathematics that would have no physical
meaning at all. And thus quantum theory merely gives us
(generally statistical) knowledge of how our instruments will
function. And from this we can make inferences that contribute to
our knowledge, for example, of how to carry out various technical
processes. That is to say, it seems, as indeed Bohr and
Heisenberg have implied, that quantum theory is concerned only
with our _knowledge_ of reality and especially of how to predict
and control the behavior of this reality, at least as far as this
may be possible. Or to put it in more philosophical terms, it may
be said that quantum theory is primarily directed towards
_epistemology_, which is the study that focuses on the question
of how we obtain our knowledge (and possibly on what we can do
with it). It follows from this that quantum mechanics can say
little or nothing about reality itself. In philosophical
terminology, it does not give what can be called an _ontology_
for a quantum system."
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D. Bohm and B.J. Hiley: _The Undivided Universe: An ontological
interpretation of quantum theory_
(Routledge, London 1993, p.1)
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[Editor's note: US-born physicist David Bohm (1917-1992) worked
on the development of the atomic bomb under J. Robert Oppenheimer
(1904-1967). Bohm joined the Princeton University physics faculty
in 1947, and shortly afterward ran into political difficulties
when he was called to testify before the House Un-American
Activities Committee, pleaded the Fifth Amendment and refused to
give evidence against his colleagues. He was cited for contempt
and threatened with prison. When his Princeton contract expired
in 1951, Bohm found himself unemployable in the US, and on the
advice of Oppenheimer, Bohm left the US. He worked at Sao Paulo
University (BR) (1951-1955) and Haifa University (IL) (1955-
1957). He then settled in the UK, and in 1961 he was appointed
Professor of Theoretical Physics at Burbeck College London, where
he served until his retirement in 1983. In 1959, Bohm and his
student Yakir Aharanov discovered the Aharanov-Bohm effect, in
which the motions of charged particles can be affected by
magnetic fields even if the particles never enter the regions in
which those fields are confined. Throughout his career, Bohm was
concerned with the foundations of quantum theory, and he is best
known as one of the proponents of "hidden variable theory". Many
physicists, including Einstein (1879-1955), did not and have not
accepted the basic indeterminacy of particle behavior postulated
by quantum mechanics. In quantum mechanics, for example,
considering radioactive decay, quantum theory proposes that
although one nucleus decays and another does not, the two nuclei
were previously in an identical state: the decay is a completely
random process, and which nucleus decays is indeterminate.
Einstein, Bohm, de Broglie (1892-1987), and others rejected the
idea that such nuclei were initially in an identical state, and
instead postulated the existence of some other property,
presently unknown, that differs for the two nuclei. This type of
unknown property is termed a "hidden variable". If such variables
existed, they would return determinacy to physics.]
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Related Background:
THEORETICAL PHYSICS: ON INTERPRETATIONS OF QUANTUM THEORY
Quantum theory is essentially a set of procedures for predicting
laboratory measurements, and it works with outstanding accuracy
provided such measurements are restricted to a range of
approximately 10^(-10) to 10^(15) atomic radii. A central
question is what are the general implications of the fact that it
works so well? This question has been debated since the various
foundations of quantum theory were established in the 1920s, and
the debate continues. But a related central question is whether
quantum theory is internally consistent, and if it is not (as
some have proposed), is there an interpretation of the theory
that will remove the apparent inconsistencies?
... ... C.A. Fuchs and A. Peres (2 installations, US IL) present
a commentary on interpretations of quantum theory, the authors
making the following points:
1) The thread common to all non-standard "interpretations"
of quantum theory is the desire to create a new theory with
features that correspond to some reality independent of potential
experiments. However, attempting to fulfill a classical world
view by encumbering quantum mechanics with various theoretical
constructs (e.g., hidden variables), without any improvement in
its predictive power, only gives the illusion of a better
understanding. The authors suggest that contrary to those
desires, quantum theory does _not_ describe physical reality.
What it does is provide an algorithm for computing
_probabilities_ for the macroscopic events ("detector clicks")
that are the consequences of experimental interventions. The
authors suggest this strict definition of the scope of quantum
theory is the only interpretation ever needed, whether by
experimenters or theoreticians.
2) The authors state they do not deny the possible existence
of an objective reality independent of what observers perceive.
In particular, there is an "effective" reality in the limiting
case of macroscopic phenomena such as detector clicks or
planetary motion: any observer who happens to be present would
acknowledge the objective occurrence of these events. However,
such a macroscopic description ignores most degrees of freedom of
the system and is necessarily incomplete. Can there also be a
"microscopic reality" where every detail is completely described?
The authors suggest no description of that kind can be given by
quantum theory.
3) The authors conclude: "To make quantum mechanics a useful
guide to the phenomena around us, we need nothing more than the
fully consistent theory we already have. Quantum theory needs no
'interpretation'."
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Physics Today March 2000
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Related Background:
DETAILS OF A PROPOSAL FOR A QUANTUM THEORY WITHOUT OBSERVERS
S. Goldstein, in the second part of a review of the current state
of the development of a quantum theory without observers, makes
the following points: 1) Several current quantum theories without
observers are completely well defined and hence provide a
conclusive refutation of Bohr's claim that such a theory is
impossible. 2) The paradoxes of quantum theory can be resolved in
a surprisingly simple way: by insisting that particles always
have positions and that they move in a manner naturally suggested
by the Schroedinger equation (e.g., the quantum mechanics of
David Bohm as amplified by John Bell). 3) The possibility of a
deterministic reformulation of quantum theory has been regarded
by many physicists as having been conclusively refuted,
particularly by the 1932 refutation of John von Neumann, but the
von Neumann proof is false, and subsequent "refutations" are not
convincing. 4) Bohmian mechanics is by far the simplest and
clearest version of quantum theory. 5) Although none of the
quantum theories without observers is Lorentz invariant, the
author believes such a theory is possible, and that the three
approaches of decoherent histories (which assumes the wave
function is not a complete description of a physical system),
spontaneous localization (which assumes spontaneous and random
collapse of wave functions), and Bohmian mechanics (which assumes
the wave function provides only an incomplete description of a
system and governs the motion of more fundamental variables) have
much to teach us about finding such a theory.
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Physics Today April 1998
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Related Background:
ON QUANTUM THEORY WITHOUT OBSERVERS
One of the fundamental questions of physics is whether pure
states (i.e., states undisturbed by avoidable noise) are states
such that the outcome of every measurement can be exactly
predicted. Classical physics is based on the proposition that the
answer to the question is yes. Orthodox quantum mechanics is a
theory based on the proposition that the answer is no, and that
we can only make precise quantitative statements about
probabilities, the limitation due to an essential interaction
between the observer and that which is being measured.
... ... S. Goldstein (Rutgers University New Brunswick, US), in
the first of a two-part review, discusses the idea of quantum
theory without observers, and suggests that despite the claims of
most of the originators of quantum theory, the appeal at a
fundamental level to observers and measurement, which is so
prominent in orthodox quantum theory, is not needed to account
for quantum phenomena. Referring to the classical Bohr-Einstein
debate, Goldstein says the debate has already been resolved in
favor of Einstein. What Einstein desired and Bohr held impossible
-- an observer-free formulation of quantum mechanics in which the
process of measurement can be analyzed in terms of more
fundamental concepts, does in fact exist, and there are many such
formulations, several of which have the potential to become a
serious program for the construction of a quantum theory without
observers.
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Physics Today March 1998
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6. ON EDWARD U. CONDON (1902-1974)
During the last 40 years of his life, in various roles, the
physicist Edward Condon became known as an educator and as a
liaison between the physics community and the US government. In
physics, Condon is perhaps best known for his early contribution
[in his PhD dissertation (1926)] to the so-called "Franck-Condon
principle", the principle that in any molecular system the
transition from one energy state to another is so rapid that the
nuclei of the atoms involved can be considered to be stationary
during the transition. In 1928, Condon and Ronald Gurney proposed
a quantum tunneling interpretation of alpha-particle emission, an
interpretation later developed independently by George Gamow, the
idea considered a considerable theoretical breakthrough in
understanding radioactive decay. In 1943, Condon worked with J.
Robert Oppenheimer in recruiting scientists to Los Alamos for the
atom bomb project. Early in the "Cold War" that followed World
War II, Condon found himself hounded by red-baiting members of
the US Congress -- a dark time not only for Condon but for many
US scientists.
... ... Jessica Wang (University of California Los Angeles, US)
presents an analysis of Edward Condon and Cold War politics, the
author making the following points:
1) On March 1, 1948, the House Committee on Un-American
Activities (HUAC) fired the opening shot in what was then the
most public Cold War political attack on a scientist. On that
day, HUAC chairman J. Parnell Thomas (Republican, New Jersey)
issued a report that labeled Edward Condon, then director of the
National Bureau of Standards, "one of the weakest links in our
atomic security." The allegations immediately made headlines
across the nation. For physicists, the news confirmed that the
binding of the Cold War to the nuclear age had extended the anti-
communist search for disloyal and subversive Americans into their
community.
2) The rise of US physicists to political prominence during
and after World War II developed in parallel with the ascendance
of the nation to superpower status. The emergence of the Cold War
and the ever-increasing demands of national security assured
physicists continued visibility and influence. But those same
conditions also brought severe restrictions on the freedom of
action of physicists. As domestic anti-communism reemerged after
World War II, protection of classified scientific information
became a national priority, and the specialized knowledge of
scientists a carefully guarded commodity. Secrecy and security
requirements, originally temporary wartime measures, became
permanent features of the lives of physicists. Scientists who
advocated arms control, international cooperation in science,
greater US-Soviet accommodation, civil rights, labor unionism,
and other causes outside the circumscribed boundaries of Cold War
politics soon found their political commitments closely
scrutinized for evidence of subversive intent.
3) Condon's unabashed liberalism, his energetic advocacy of
arms control and internationalism in science, and his high-level
government profile placed him on a collision course with HUAC
during the formative years of the post-World War II "red scare".
For Condon, confrontation with HUAC meant years of public
scrutiny and political harassment. For science as a whole, his
ordeal exemplified the larger struggles between science and
politics that became a part of the lives of physicists during the
Cold War era.
4) In a career that ultimately spanned 5 decades, Condon
published more than 90 papers in such diverse fields as atomic
physics, solid-state physics, and the physics of microwaves and
radio waves. He also co-authored several well-known textbooks,
including the first English-language textbook on quantum
mechanics (with Philip Morse in 1929), and the classic _The
Theory of Atomic Spectra (with G.H. Shortley in 1936).
5) By the end of 1948, Condon emerged unscathed and
victorious from his confrontation with HUAC, with President
Truman himself publicly defending Condon. J. Parnell Thomas won
his congressional race that year but was indicted for payroll
padding shortly thereafter. Thomas pleaded no contest, resigned
from Congress in disgrace, and spent 9 months in federal prison.
In later years, Condon delighted in referring to J. Parnell
Thomas as "ex-convict Thomas".
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[Editor's note: As in this case, history often provides a sense
of justice done. The post-World War II, "red scare", however,
persisted long after J. Parnell Thomas under the aegis of Richard
Nixon and Joseph McCarthy, and many scientists -- physicists,
chemists, biologists -- had their careers destroyed by
politicians essentially more "un-American" than any of the
scientists they publicly attacked.]
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Physics Today 2001 December
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7. ACCELERATED GRAY MATTER LOSS IN EARLY-ONSET SCHIZOPHRENIA
P.M. Thompson et al (University of California Los Angeles, US)
discuss gray matter loss in schizophrenia, the authors making the
following points:
1) Little is known about the profile of brain change in
adolescence and its modulation in diseases with adolescent onset.
Schizophrenia, for example, has typical onset in late adolescence
or early adulthood, and cases occurring in childhood or early
adolescence present unique opportunities to study disease
development during adolescence. Childhood-onset schizophrenia is
a severe form of the disorder that appears to be clinically and
neurobiologically continuous with the later onset illness. The
causes of schizophrenia are not known, but it is increasingly
considered a neurodevelopmental disorder. Both early (prenatal)
and later abnormalities of brain development have been proposed,
but neither the anatomical pattern nor the timing of these
developmental events has been established.
2) The authors report that with the use of brain mapping
algorithms, they detected striking anatomical profiles of
accelerated gray matter loss in very early-onset schizophrenia.
Surprisingly, deficits moved in a dynamic pattern, enveloping
increasing amounts of cortex throughout adolescence. The earliest
deficits were found in parietal brain regions supporting
visuospatial and associative thinking. In temporal regions, gray
matter loss was completely absent early in the disease but became
pervasive later. The authors suggest their results reveal a
shifting pattern of tissue loss in schizophrenia, a changing
profile that implicates both genetic and non-genetic patterns of
deficits.
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Proc. Nat. Acad. Sci. 2001 98:11650
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Related Background:
IN BRIEF: BRAIN VOLUME CHANGES IN SCHIZOPHRENIA:
Researchers report the results of a study designed to determine
if brain morphological changes previously observed in patients
with schizophrenia progress over time and whether such
progression is related to the severity of the course of the
illness. In a controlled study of 24 schizophrenic patients and
25 controls, the study involving 2 brain magnetic resonance
imaging scans on average 4 years apart, it was found that
schizophrenic patients exhibited more rapid brain volume decline
than control subjects in various brain regions, as well as more
rapid cerebrospinal fluid expansion in various brain regions.
There were correlations with severity of illness and length of
time hospitalized. The researchers conclude their study reveals
that patients with chronic schizophrenia exhibit accelerated
frontotemporal cortical gray matter decline and cortical sulcal
and lateral ventricular expansion. In addition, greater clinical
severity of the disorder is associated with faster rates of
frontotemporal brain volume changes. The authors suggest these
observations are consistent with a progressive pathophysiological
process, but the observations need to be replicated on a larger
sample.
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Arch. Gen. Psychiat. 2001 58:148
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Related Background:
IN BRIEF: SCHIZOPHRENIA GENETICS RESEARCH
Sanders and Gejman (2001) review recent progress in research on
the genetic basis of schizophrenia. Schizophrenia is a
devastating disorder affecting 1 percent of the population
worldwide, and the elucidation of the biology of schizophrenia
will constitute a development of great medical and historic
importance. The study of familial schizophrenia was instrumental
in opening the field of psychiatry to genetic inquiry, and
together with twin and adoption studies helped forge the field of
psychiatric genetics. Over the past century, studies have
consistently demonstrated that both genetic and non-genetic
factors play a significant role in the etiology of schizophrenia.
Currently, a large number of molecular and genomic database
tools, an understanding of complex genetics, and a convergence of
results from genetic mapping of several chromosomal regions all
contribute to optimism that genes involved in the pathogenesis of
schizophrenia will be characterized in the near future.
Identification of susceptibility genes, their products, and
interacting proteins will likely illuminate pathways to illness,
provide more specific pharmacological targets, and lead to
improved understanding of environmental contributions to
susceptibility. The hope is that this knowledge will further
advance clinical progress in treatment and even prevention of
schizophrenia.
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J. Am. Med. Assoc. 2001 285:2831
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Related Background:
ON RETROVIRUSES AND THE PATHOGENESIS OF SCHIZOPHRENIA
The diagnoses of various behavioral disorders are for the
most part made in the absence of defined etiology, and because of
this there is a necessary focus on symptoms rather than causes,
and the diagnostic categories are consequently often ambiguous
and labile. Schizophrenia is a serious mental disease (or complex
of mental diseases) that occurs worldwide with a prevalence
ranging from 0.2% to 1%. Its chief characteristic is a chronic
impairment of function involving disturbances of thought,
perception, feelings, and behavior, particularly the appearance
of the classical psychotic symptoms of delusions, hallucinations,
and logic dysfunction. A major worldwide mental health problem,
schizophrenia has been the focus of an enormous number of
research studies during the past century, and nearly every
possible etiology has been proposed to explain its pathogenesis.
The idea that viruses may be involved in the etiology of
schizophrenia is not new, but as molecular biology continues to
advance in techniques and insights, evidence and considerations
of a virus involvement in schizophrenia continue to recur.
When viruses are categorized in terms of their genomes,
there are two general types: a) viruses with a DNA genome (DNA
viruses), and b) viruses with an RNA genome (RNA viruses). RNA
viruses are unique: only in these viruses do we find genomes
consisting of RNA; all other biological entities, DNA viruses,
bacteria, plant cells, animal cells, etc., contain DNA genomes.
There are more than 2500 groups of different viruses now
recognized and at least partially characterized. In each case,
for both DNA and RNA viruses, once it enters the host cell, the
general challenge for the virus is the same: directly or
indirectly, the viral genome must bring about the production of
the *messenger RNAs needed by the host ribosomes to produce the
specific proteins necessary for replication of the complete
virus.
With DNA viruses, the DNA genome acts as the template for
the production of messenger RNA. With RNA viruses, however, the
process is more complicated.
In general, with some types of RNA viruses, the RNA genome
("plus-sense"; "positive-strand") can itself act as messenger RNA
for host *ribosomes; while other types of RNA viruses, the RNA
genome ("minus-sense"; negative-strand) must first produce a
complementary RNA, which then acts as messenger RNA for the host
ribosomes. The replication process in minus-sense RNA viruses is
complex, since host cells do not carry enzymes that can
polymerize complementary RNA from an RNA template, and such
viruses therefore must carry their own special enzymes ("RNA-
dependent transcriptases") to achieve this synthesis.
A third and special type of RNA virus is the so-called
"retrovirus", of which there are many versions. Retroviruses are
single-stranded RNA viruses that have an enzyme called reverse
transcriptase, and with this enzyme the viral RNA is used as a
template to produce viral DNA from host-cellular material. This
DNA is then incorporated into the host cell's genome, where it
codes for the production of messenger RNA and the ultimate
synthesis of viral components. The HIV virus, for example, is a
retrovirus.
Concerning retroviruses, if the incorporation of the viral
DNA into the host cell DNA takes place in *germ-line cells
(oocytes) or early embryos, then the retroviral genes become
"endogenous" -- they become a permanent part of the organismic
genome and are reproduced from generation to generation. It is
believed by some researchers that all vertebrates, for example,
have endogenous retroviruses that are the "footprints" of ancient
retroviral infections. For the most part, the significance of
endogenous retroviruses is unclear, but there is some evidence
suggesting they may contribute to the development of diseases in
several animal species and possibly also in humans.
It is important to emphasize that the nomenclature here is
not rigorous, since an endogenous retrovirus is not an actual
virus, but one or more pieces (complete or incomplete genes) of a
retroviral genome embedded in a host genome. These endogenous
retroviral genes may be eternally dormant, sporadically activated
and repressed, or always operational. A disease related to the
activation of an endogenous retrovirus is therefore not an
"infectious" disease in the classical sense, although the
original introduction into the host germ-line of the retroviral
genetic material may indeed have involved an infection. As a
further complication, there is evidence that in some diseases
interactions of endogenous retroviral genes and infectious
(exogenous) retroviral genes may occur.
... ... David A. Lewis (University of Pittsburgh, PA) presents a
commentary on some recent work (H. Karlsson et al: Proc. Natl.
Acad. Sci. US 2001 98:4634) connecting retroviruses to
schizophrenia, the author (Lewis) making the following points:
1) The author (Lewis) points out that the contribution of
genetic factors to the risk of developing schizophrenia has been
demonstrated in family, twin, and adoption studies. In contrast
to the 1 percent lifetime incidence of schizophrenia in the
general population, the incidence of schizophrenia in the
relatives of affected individuals is approximately 2 percent in
3rd-degree relatives, 2 to 6 percent in 2nd-degree relatives, and
6 to 17 percent in 1st-degree relatives. When one member of a
twin pair has the illness, the risk of schizophrenia in the other
twin is approximately 17 percent for fraternal twins and
approaches 50 percent for identical twins. Furthermore, in
adoption studies, the risk of schizophrenia is related to the
presence of the illness in the biological but not in the adoptive
parents. Although regions on a number of chromosomes have been
implicated as sites of potential susceptibility genes, the
specific genes (or combination of genes) that confer risk for
schizophrenia have not yet been identified.
2) The author (Lewis) points out that a number of
environmental factors, usually factors occurring early in life,
also seem to increase the risk for schizophrenia. For example,
severe maternal malnutrition during the first trimester or
maternal influenza during the second trimester of pregnancy are
apparently associated with a doubling of the relative risk of
schizophrenia, and *perinatal brain damage or maternal
*preeclampsia may increase the risk by 7- to 9-fold.
3) The author (Lewis) points out that retroviruses have been
considered possible etiological agents in schizophrenia for some
time, at least since 1984, because retroviruses could apparently
explain some of the enigmatic aspects of the illness. For
example, the differential activation and reintegration of
endogenous retroviruses during early development may lead to
altered brain function later in life, providing a potential link
between risk factors identified in utero and perinatal risk
factors on the one hand, and the onset of clinical schizophrenia
during the late second and third decades of life on the other
hand. In addition, an endogenous retroviral etiology could
provide explanation for the continued prevalence of schizophrenia
despite the reduced fecundity associated with the illness, and
for the relatively uniform incidence of schizophrenia throughout
the world.
4) Although evidence of an association between retroviruses
and schizophrenia has not been available, Karlsson et al (2001)
now report the identification of nucleotide sequences homologous
to retroviral "pol" (polymerase) genes in the cerebrospinal fluid
of 28.6 percent of subjects with schizophrenia of recent onset (N
= 35), and in 5 percent of subjects with chronic schizophrenia (N
= 20). In contrast, such retroviral sequences were not found in
any individual with non-inflammatory neurological illness (N =
22) or in normal control subjects (N = 30).
5) The author (Lewis) states: "Although the observations of
the study of Karlsson et al are interesting, their potential
significance for our understanding of the etiopathogenesis of
schizophrenia rests on the replication of these findings in other
cohorts of subjects. Independent replication is an axiom in all
areas of medicine, but it is particularly important in studies of
schizophrenia, where the history of the field includes many
examples of exciting findings that subsequently either failed to
be confirmed in other cohorts of subjects with the disorder or
proved to lack specificity to the illness."
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Proc. Nat. Acad. Sci. 2001 98:4293
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Notes:
... ... *messenger RNA: (mRNA) The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
... ... *ribosomes: A ribosome (not to be confused with riboZYME)
is a small particle, a complex of various ribonucleic acid
component subunits and proteins that functions as the site of
protein synthesis. In general, ribosomes read the messenger RNA
template to produce specific polypeptide sequences by
polymerizing amino acids.
... ... *germ-line cells: In general, "germ-line" cells are
reproductive cells, or any cells giving rise to reproductive
cells such as oocytes (egg cells) or spermatocytes (sperm cells).
All other cells are called "somatic cells". Mutations (or
introduction of foreign genes) in germ-line cells are carried
from the parent generation to the offspring generation, while
mutations in somatic cells are not transferred to the next
generation.
... ... *perinatal: Refers to the time-frame before, during, and
immediately after birth.
... ... *preeclampsia: In general, the development of
hypertension during pregnancy.
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8. ON MULTIPLE SCLEROSIS
A. Chang et al (Lerner Research Institute, US) discuss multiple
sclerosis, the authors making the following points:
1) Multiple sclerosis is an inflammatory disease of the
central nervous system that destroys myelin, the insulation that
surrounds axons. Oligodendrocytes (the cells that produce myelin)
and nerve fibers are also destroyed. Most patients with multiple
sclerosis have an initial relapsing-remitting course for 5 to 15
years that then takes a secondary progressive course of
irreversible neurologic disability. Relapses result from
inflammation and demyelination, whereas restoration of nerve
conduction and remission is accompanied by resolution of
inflammation, redistribution of sodium channels on demyelinated
axons, and remyelination.
2) Demyelination is not always permanent in multiple
sclerosis. Remyelination during early stages of the disease
process has been documented by histologic analysis of tissue
specimens from both biopsy and postmortem examination. Most
chronic lesions of multiple sclerosis, however, are not
remyelinated. Remyelination requires generation of new
oligodendrocytes. Oligodendrocyte progenitor cells have been
characterized in developing brain, normal adult human brain, and
chronic lesions of multiple sclerosis.
3) The authors report a study investigating in human
patients the frequency of distribution and configuration of
oligodendrocytes in chronic lesions of multiple sclerosis to
determine whether these factors limit remyelination. From their
results, the authors conclude that premyelinating
oligodendrocytes are present in chronic lesions of multiple
sclerosis, so remyelination is not limited by an absence of
oligodendrocyte progenitors or their failure to generate
oligodendrocytes. The authors suggest their findings indicate
that in the chronic lesions of multiple sclerosis, the axons are
not receptive for remyelination.
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New Engl. J. Med. 2002 346:165
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9. ON THE NUCLEAR ENVELOPE
M. Dreger et al (Free University of Berlin, DE) discuss the
nuclear envelope, the authors making the following points:
1) The identification of predicted gene products at the
protein level bridges the gap between genome sequencing data and
protein function, and is referred to as "functional genomics". In
this domain, the combination of subcellular fractionation and
mass spectrometry techniques ("subcellular proteomics") is a
powerful strategy for the initial identification of previously
unknown protein components and for their assignment to particular
subcellular structures.
2) The nuclei of eukaryotic cells contain several
compartments defined by their morphology in electron microscopy
and by the distribution of a limited number of marker proteins.
Because the structural and functional organization of nuclei
seems to be intimately linked to epigenetic control of gene
expression, the characterization of such nuclear compartments at
the molecular level is of great importance. The nuclear envelope
is one of the least characterized compartments of the nucleus. It
comprises an outer and inner nuclear membrane, the pore membrane,
the nuclear pore complexes, and the nuclear lamina.
3) The subcompartments of the nucleus differ with respect to
their protein components, but a thorough molecular
characterization has not yet been achieved. Furthermore, a 2-
dimensional separation of nuclear envelope membrane proteins by
various separation techniques fails because the separation system
discriminates against integral membrane proteins. Therefore, the
characterization of the nuclear envelope at the protein level
must overcome general analytical challenges. The nuclear envelope
contains several compartments enriched in different subsets of
integral membrane proteins and multiprotein complexes. Many of
the integral membrane proteins interact with a stable network of
structural proteins and cannot be extracted by detergents, a
problem also relevant for the analysis of any other complex
membrane protein structure.
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Proc. Natl. Acad. Sci. 2001 98:11943
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10. ON CHROMATIN
In the nuclei of all eukaryotic cells, genomic DNA is highly
folded, constrained, and compacted by histone and nonhistone
proteins in a dynamic polymer called "chromatin". The distinct
levels of chromatin organization are dependent on the dynamic
higher order structuring of "nucleosomes", which represent the
basic repeating unit of chromatin.
... ... N. Gilbert and J. Allan (University of Edinburgh, UK)
discuss chromatin fibers, the authors making the following
points:
1) When fragments of chromatin are isolated from cells and
maintained under ionic conditions comparable to those in the
nucleus, the chromatin fragments are invariably found to be
folded into higher-order fibers. Structural studies on such bulk
material have formed the basis for a variety of models that are
proposed to explain the manner in which chains of nucleosomes are
packaged into the higher-order state. However, the ubiquitous and
uniform character of the higher-order chromatin fiber suggested
by these models tends to mask the fact that the higher-order
chromatin fiber must be an adaptable structure capable of
undergoing dynamic structural transitions. Such properties are
required to facilitate the unfolding processes presumed to be
essential for gene activation and chromosome replication. On the
other hand, the chromatin fiber must also have the capacity to
adopt an inert character required to maintain genes in a state of
sustained repression and to provide local chromosomal domains
with distinctive architectures within which specific chromosomal
structures (e.g., the centromere) can exist.
2) Despite these expectations, studies on isolated higher-
order chromatin fibers have failed to reveal a diversity of
structure compatible with the diversity of function. For example,
chromatin fibers containing globin gene sequences isolated from
erythroid cells in an activated state have physical properties
equivalent to both bulk and transcriptionally inactive chromatin
fibers. The presence of nucleosome-free hypersensitive sites
disrupts the fiber, but between these distinctive regions the
chromatin appears to be typically folded. Within the cell, the
higher-order chromatin fiber does unfold during transcription,
but maintenance of this state is notably transient because the
inhibition of polymerase activity leads to a rapid reformation of
the folded state. Thus, with regard to structural criteria, it
appears that chromatin fibers containing active gene sequences
cannot be distinguished from bulk or inactive chromatin fibers
once they are removed from the nucleus.
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Proc. Nat. Acad. Sci. 2001 98:11949
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11. GENES, DIFFERENTIATION, AND DEVELOPMENT
In general, the term "epigenetics" refers to influences on gene
expression other than those produced by direct changes in the
nucleotides of the genome. In recent years, it has become
increasingly apparent that in living cells complex epigenetic
processes that control gene expression are as important as the
genome code itself in determining cellular biochemistry and
physiology, cell differentiation, and the development of tissues,
organs, and the organism.
... ... M. Azim Surani (University of Cambridge, UK) discusses
genes and differentiation, the author making the following
points:
1) Development is a remarkably orderly process, beginning
with a totipotent zygote and ending with an array of specific
differentiated cell types in adults. Approximately 40,000 genes
are needed to build a human being possessing approximately 200
histologically distinct cell types, and these categories can be
subdivided further into a myriad of specialized cell types. These
cells fulfill precise functions that are as diverse as mounting a
defense against diseases, regulating energy input-output, and
building neural networks that allow us to interact with our
environment.
2) Once a cell is fully differentiated, this state is
strikingly stable. Regardless of how different a neuron is from a
liver cell (hepatocyte), most cells retain an intact genome with
the full complement of genes that are present at the beginning in
the zygote. This simple concept of profound significance for
development had its origin in the work of Hans Spemann (1869-
1941). The distinguishing features of cells arise from an orderly
selection of genes that are expressed while the remainder of
genes are switched off.
3) The genetic network that controls developmental decisions
is beginning to be defined. The ability to acquire and inherit
gene-expression patterns efficiently is also crucial to the
individual history of cell differentiation. There are potential
mechanisms that can allow a differentiated cell to perpetuate the
"molecular memory" of the developmental decisions that created
it. We know that this occurs without alterations or deletions of
any DNA sequences, but rather by epigenetic mechanisms that
propagate appropriate patterns of gene expression. These
mechanisms involve heritable but potentially reversible
modifications of DNA, primarily methylation of cytosine-guanine
dinucleotide. The binding of specific protein complexes to DNA
also occurs, resulting in stable and heritable chromatin
structures that ensure efficient silencing of genes that are no
longer required for determination of cell fate -- i.e., allowing
expression of only those genes that define properties of specific
differentiated cell types.
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Nature 2001 414:122
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12. ON SIMULATIONS OF BIOMOLECULAR PROCESSES
Herman J. Berendsen (University of Groningen, NL) discusses
simulations of biomolecular processes, the author making the
following points:
1) Biomolecular process present three problems for
simulation on the atomic level: a) Such processes involve
hundreds of thousands of atoms, often in intricate interactions
that are difficult to simplify. b) Such processes span a wide
range of time scales: primary events (e.g., vision or
photosynthesis) occur within picoseconds, enzymatic and
regulatory processes take milliseconds, and protein folding and
structural reorganizations may exceed seconds. c) The small
driving forces that cause molecular changes result from large and
opposing energetic effects, requiring careful fine-tuning of the
force-fields that describe interatomic interactions.
2) Current simulations are limited to system sizes of
approximately 100,000 atoms, time scales of approximately 100
nanoseconds, and classical dynamics with simple and pair-additive
interactions. Quantum mechanics can also be incorporated, but at
the expense of system size or time-scale.
3) The future will see rapid progress in solving all three
problems. Within existing limitations, however, most biological
processes cannot be simulated in "real time". Even for processes
that do occur on a 100-nanosecond time scale, it is not
sufficient to simulate an event -- for example, the folding of a
peptide into a helix -- once. Statistics must be collected under
varying conditions. In practice, one can either simulate
processes that do occur on the time scale attainable for
simulation with full atomic detail, or one can resort to
approximations in system size, detail of description, or accuracy
of dynamics. The approximation approach is the only possible way
to proceed for most processes, but does involve approximations
that need thorough testing, and there is also a danger that the
chosen approximations bias the results.
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Science 2001 294:2304
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13. ON NANOWIRE BUILDING BLOCKS
Y. Huang et al (Harvard University, US) discuss nanowire building
blocks, the authors making the following points:
1) Fundamental physical constraints and economics are
expected to limit continued miniaturization in electronics by
conventional top-down manufacturing during the next one or two
decades and have thus motivated efforts worldwide to search for
new strategies to meet expected computing demands of the future.
Bottom-up approaches to nanoelectronics, where the functional
electronic structures are assembled from well-defined nanoscale
building blocks, such as carbon nanotubes, molecules, and/or
semiconductor nanowires, have the potential to go far beyond the
limits of top-down manufacturing. For example, single-walled
carbon nanotubes have been used as building blocks to fabricate
room-temperature field-effect transistors, diodes, and an
inverter that represents a key component for logic operations.
2) However, the inability to control whether such nanotubes
are semiconducting or metallic makes specific device fabrication
largely a random event and poses a serious issue for integration
beyond the single-device element level. A potential solution to
the problem of coexisting metallic and semiconductor nanotubes
involves selective destruction of metallic tubes, although such
an approach requires extensive top-down lithography and
subsequent processing to implement.
3) The authors report a bottom-up approach in which
functional device elements and element arrays have been assembled
from solution through the use of electronically well-defined
semiconductor nanowire building blocks. The authors demonstrate
that crossed nanowire p-n junctions and junction arrays can be
assembled with over 95 percent yield and with controllable
electrical characteristics, and in addition, that these junctions
can be used to create integrated nanoscale field-effect
transistor arrays with nanowires as both the conducting channel
and gate electrode. Nanowire junction arrays have been configured
by the authors as key OR, AND, and NOR logic-gate structures with
substantial gain and have been used to implement basic
computation.
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Science 2001 294:1313
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14. ON SOLAR ENERGY AND INORGANIC PHOTOCHEMISTRY
Nathan S. Lewis (California Institute of Technology, US)
discusses solar energy devices, the author making the following
points:
1) A stable and efficient material that uses sunlight to
split water into hydrogen and oxygen would be of great practical
significance. Water and sunlight are both renewal resources, and
both cheap. In addition, one of the end products of the splitting
process, H(sub2), is a clean-burning fuel that produces water as
the waste product.
2) There are 3 fundamental requirements for any system for
converting and storing solar energy: a) Sunlight must be
efficiently absorbed to produce excited electron states in the
light-absorbing material, the photocatalyst. b) To obtain
directed work, either chemical or electrical in form, the
photoexcited electron and its accompanying electron vacancy must
be separated in space to prevent their recombination, which
produces heat and wastes energy. c) The photoexcited charge must
be energetically and kinetically able to perform a desired
chemical transformation, for instance splitting water.
Furthermore, these charges must not result in undesirable end
products, such as heat, or chemically transform or otherwise
degrade the photocatalyst. Satisfying all these requirements
simultaneously is an extremely difficult prospect.
3) A popular approach is to use semiconductors as the light
absorbers. Semiconducting solids generally have broad and strong
optical absorption characteristics, meeting the first requirement
for solar energy conversion. Such solids also generally satisfy
the second requirement, because effective charge separation is
facilitated by electric fields at the interface between a
semiconductor and selected liquid electrolytes. The key
requirement, and the problem not yet solved, is an efficient
splitting of water by such a system.
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Nature 2001 414:589
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15. ON CONTROLLING THE SHAPE OF NANOPARTICLES
R. Jin et al (Northwestern University, US) discuss controlling
the shape of nanoparticles, the authors making the following
points:
1) Particle size determines many of the physical and
chemical properties of nanoscale materials, including
luminescence, conductivity, and catalytic activity. Colloid
chemists have achieved excellent control over particle size for
several spherical metal and semiconductor compositions, which has
led to the discovery of quantum confinement in colloidal
nanocrystals and to the use of such structures as probes for
biological and medical diagnostic applications, LED materials,
lasers, and Raman spectroscopy-enhancing materials.
2) However, the problem of synthetically controlling
particle shape has been only incompletely solved. Some physical
and solid-state chemical deposition methods have been developed
for making semiconductor and metal nanowires, nanobelts, and
nanodots. Currently, there are also a variety of methods for
making rods with somewhat controllable aspect ratios using
seeding approaches and electrochemical and membrane-templated
syntheses. Some solution methods also exist for making cubes,
pyramids, triangles, nanoprisms, etc., of various nanoscale
inorganic materials, but in most cases the yield of a desired
shape is relatively small.
3) The authors report a photoinduced method for converting
large quantities of silver nanospheres into triangular
nanoprisms. The photoprocess has been investigated and
characterized by time-dependent UV-visible spectroscopy and
transmission electron microscopy, allowing the observation of
several key intermediates in and characteristics of the
conversion process. This light-driven process results in a
colloid with distinctive optical properties that directly relate
to the nanoprism shape of the particles. The authors report that
these nanoprisms exhibit scattering in the red, which could be
useful in developing multicolor diagnostic labels on the basis
not only of nanoparticle composition and size but also on the
basis of nanoparticle shape.
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Science 2001 294:1901
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OTE NEW CARRIERS OF SENSITIZERS IN PHOTODYNAMIC THERAPY
S.D. Baugh et al (Columbia University, US) discuss photodynamic
therapy, the authors making the following points:
1) In photodynamic therapy, a dye such as porphyrin or a
phthalocyanine is administered to a patient along with
irradiation. The excited-state dye converts triplet oxygen to the
singlet form, which is lethal to cells. Thus, light directed into
the area of a tumor can lead to the destruction of cancer cells
if the photosensitizer is present.
2) One problem with photodynamic therapy is the
accessibility of the tumor to light. Another problem concerns the
desirability of localizing the photosensitizer at the tumor site,
since patients with a photosensitizer distributed throughout
their systems can experience serious toxic effects in sunlight,
for example. One can attempt to target the photosensitizer to the
cancer cells by using cancer-specific antibodies, but the use of
a foreign protein may cause its own problems.
3) It has been suggested that a cyclodextrin dimer could
play a useful role in photodynamic therapy if the dimer were able
to bind and solubilize an otherwise insoluble photosensitizer.
The solubilized hydrophilic complex might not easily be taken up
by cells, including cancer cells. If the dimer had a linkage that
was cleavable by a singlet oxygen, the complex of the
cyclodextrin dimer with the photosensitizer could liberate the
hydrophobic photosensitizer in a light beam when the linker
cleaved. The photosensitizer could then enter the cells -- or at
least bind to proteins -- in the region and not be diffusible
throughout the body.
4) The authors report the synthesis of several
phthalocyanines carrying hydrophobic components, these compounds
binding to a group of cyclodextrin dimers with a carbon-carbon
double bond in the linker. The complexes are soluble in water. On
irradiation in the presence of oxygen, the singlet oxygen
produced cleaves the olefinic linkers in the complexes, resulting
in precipitation of the sensitizers. This process concentrates
the sensitizers in the light beam, and the authors suggest the
process may have useful potential in photodynamic therapy.
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J. Am. Chem. Soc. 2001 123:12488
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17. INCORPORATION OF QUANTUM DOTS IN COLLOIDS
W. Wang and S.A. Asher (University of Pittsburgh, US) discuss
customized nanoparticles, the authors making the following
points:
1) Nanoscale metal and semiconductor particles are of
current interest because they mark a material transition range
between quantum and bulk properties. With decreasing particle
size, bulk properties are lost as the continuum of electronic
states becomes discrete (the quantum size effect) and as the
fraction of surface atoms becomes large. The electronic and
magnetic properties of metallic nanoparticles and nanoclusters
show new characteristics that can be utilized in novel
applications in areas that range from nonlinear optical switching
and catalysis to high-density information storage.
2) Numerous methods have been developed to synthesize metal
nanoparticles. A major difficulty with scale-up of these methods
is that the metal colloid stability is often controlled by
electrostatic interactions across the Debye double layer and
sterically through adsorption of steric stabilizing agents such
as polymers and surfactants. As a consequence, such metal
colloids are extremely sensitive to their environment.
3) One way to improve the stability of metal nanoparticles
is to coat them with silica, which is very resistant to
coagulation, even at high volume fractions. It has been reported
that particles of noble metals such as Ag and Au can be coated
with silica shells, but these procedures usually involve a multi-
step process, and only single metal particle cores could be
coated.
4) The authors report the development of a new method to
fabricate nanocomposite silicon dioxide spheres (approximately
100 nanometers in diameter) containing homogeneously dispersed Ag
quantum dots (2 to 5 nanometers in diameter). The inclusion
morphology is controlled through the timing of the photochemical
reduction of silver ions during hydrolysis of tetraethoxysilane
in a microemulsion.
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J. Am. Chem. Soc. 2001 123:12528
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18. ON NANOPARTICLE SYSTEMS AND RESEARCH
S. O'Brien et al (Columbia University, US) discuss nanoparticles,
the authors making the following points:
1) The physical properties of materials as they progress
from the bulk to the nanoscale regime (1 to 100 nanometers)
continue to be of immense interest and increasing importance for
future technological applications.
2) Nanocrystals display properties generally found to be
different from the bulk material or from the atomic or molecular
species from which they can be derived, and examples of this
phenomenon are diverse. The study of semiconductor nanocrystal
quantum dots is now a well-established field yielding rich,
useful, and applications-oriented research. A coherent field of
study currently emerging is the systematic examination of
nanocrystal oxides with the aim of producing nanoparticles with
narrow size distributions and size tunability in the nanoscale
regime. Among the important characteristics of nanoparticle
systems are facile manipulation and reversible assembly, which
allow for the possibility of incorporation of nanoparticles into
electric, electronic, or optical devices. Such "bottom up" or
"self-assembly" approaches are the benchmarks of nanotechnology.
3) Ferroelectric materials are under investigation because
of the prospect that the stable polarization states of these
systems could be used to encode the 1 and 0 of the Boolean
algebra forming the basis of memory and logic circuitry. The
family of complex ferroelectric oxides such as BaTiO(sub3),
Pb(Zr,Ti)O(sub3), and (Ba,Sr)-TiO(sub3) has far-reaching
potential applications in the electronics industry for
transducers, actuators, and high-k dielectrics.
4) Ferroelectricity is found in crystals exhibiting
spontaneous polarization and hysteresis of dielectric
displacement when the crystal is subjected to an applied electric
field. The precise nature of ferroelectricity at the nanoscale,
e.g., critical size-dependent suppression in particles and thin
films, is much debated in the literature, and quantitative
research in this area requires controlled synthesis of tunable
systems of nanoparticles.
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J. Am. Chem. Soc. 2001 123:12085
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19. CONFLICTS OF INTEREST IN BASIC SCIENTIFIC RESEARCH
Donald Kennedy (Science Magazine, US) discusses conflicts of
interest in basic scientific research, the author making the
following points:
1) In the Bayh-Dole Amendments of 1980 -- the "Homestead
Act" of modern US basic scientific research -- Congress gave up
federal rights to the intellectual property resulting from work
supported by government funds. Instead, those rights could be
claimed by the institutions themselves or by individual
scientists where institutional rules permitted it. Bayh-Dole thus
did for intellectual property what the Homestead Act of 1862 had
done for real property. Just as happened in the 19th century,
further statutory changes extended the incentives for
privatization, including modifications in the tax laws that
reduced the tax on capital gains and allowed more generous
deductions. The resulting flood of venture capital has resulted
in huge private investments to support the kind of research that
had previously lived only in the public sector. Universities set
up offices of technology licensing, and faculty hurried to
participate in new start-ups.
2) All this has brought some major benefits along with
significant costs. Hundreds of companies are now contributing
important nonproprietary research findings at no cost to the
taxpayer. We have two human genome projects, years sooner than we
would have had either one, thanks to a $300 million private
investment. Industry job growth has helped many of our students
and colleagues survive a discouraging academic employment sector.
On the cost side, new problems of conflict of interest, licensing
policy, royalty distribution, and the propriety of commercial
relationships have arisen for faculty members and university
administrators alike.
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Science 2001 294:2249
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20. MALIGNANT MELANOMA: AN UPDATE
A. Slominski et al (University of Tennessee, US) discuss recent
research on malignant melanoma, the authors making the following
points:
1) Melanoma is not genetically homogeneous, and the existing
differences between pathologic categories, particularly in areas
such as type of growth phase (radial vs. vertical growth), total
vertical dimension, ulceration of primary tumor, and metastatic
process, have profound prognostic and therapeutic implications.
2) Chromosomal aberrations and gene mutations are found in
both sporadic and familial melanomas. Among the most important
are those affecting the 9p21 gene, which contains the p16 locus,
a site known to be critical for normal progression of the cell
cycle. Aberrant p16 expression is associated with more aggressive
behavior of the malignancy.
3) Melanoma cells possess a remarkable repertoire of
biosynthetic capacities represented by the production of
hormones, growth factors, and their receptors that may sustain
and accelerate tumor development and progression. For example,
expression of the tumoral products alpha-melanocyte-stimulating
hormone and adrenocorticotropic hormone is regulated in vitro by
ultraviolet light, a known carcinogen.
4) Melanomas differ from other tumors in their intrinsic
capability to express melanogenic enzymes with the corresponding
structural proteins to actually synthesize melanin.
Melanogenesis-related proteins are rapidly becoming of
significance in the clinical arena, being used not only as
diagnostic markers, but also as potential targets for melanoma
therapy.
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Arch. Pathol. Lab. Med. 2001 125:1295
J. Am. Med. Assoc. 2002 287:172
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Related Background:
ON CHILDHOOD SUNBURN AND ADULT MELANOMA
F.P. Noonan et al (George Washington University, US) discuss
early sunburn and adult melanoma. Retrospective epidemiological
data have indicated that cutaneous malignant melanoma may arise
as a consequence of intense and intermittent exposure of the skin
to ultraviolet radiation, particularly in children, rather than
from cumulative lifetime exposure associated with other forms of
skin cancer. The authors report the use of a genetically
engineered mouse model to demonstrate that a single dose of
burning ultraviolet radiation in neonates, but not adults, is
necessary and sufficient to induce tumors with high penetrance
that are reminiscent of human melanoma. The authors suggest their
results provide experimental support for epidemiological evidence
that childhood sunburn poses a significant risk for development
of this potentially fatal disease. Concerning the question of why
neonatal mouse skin is so sensitive to ultraviolet-induced
melanogenesis, the authors point out that since melanocyte-
precursor cells are more abundant in neonatal than in adult skin
and more proliferative under stress, ultraviolet light exposure
may stimulate proliferation of DNA-damaged neonatal progenitors
and thus facilitate melanogenesis. Also, early exposure to
intense ultraviolet radiation might affect the developing immune
system, promoting future tolerance to arising melanoma. However,
the authors also suggest that caution is called for in
extrapolating these results to sunburn in children. The
difference in thickness between mouse and human skin could affect
the penetration of ultraviolet radiation. Moreover, the human age
equivalent to a 3.5-day-old neonatal mouse cannot be precisely
calculated.
-----------
Nature 2001 413:271
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Related Background:
MEDICAL BIOLOGY: PATHOGENESIS OF UV INDUCTION OF MELANOMAS
Skin cancers, predominantly *basal-cell and *squamous-cell
*carcinomas, have accounted for an estimated 40 percent of all
cancers in the US in recent years, and the frequency of these
cancers has been increasing. The most common fatal skin cancer is
*melanoma, and this has also increased, indeed by a factor of
approximately 15 in the past 60 years. In 1997, more than 40,000
new cases of melanoma were diagnosed in the US, with more than
7200 fatalities.
... ... B.A. Gilchrest et al (Boston University, US) present an
extensive review of current research concerning the pathogenesis
of melanoma induced by UV radiation, the authors making the
following points:
1) The factors underlying the rapid increase in the
incidence of skin cancer are incompletely understood, but
increased total exposure to the Sun, and in the case of melanoma,
altered patterns of exposure, are strongly implicated.
2) The risk of melanoma is higher in fair-skinned people,
especially those with blond or red hair who sunburn and freckle
easily, than in people with darker complexions. The incidence of
melanoma among whites is inversely related to the latitude of
residence, with the world's highest incidence in Australia, a
subtropical country with a largely Celtic population. Conversely,
melanomas are uncommon in darker-skinned people.
3) The epidemiologic evidence implicating solar exposure in
the causation of melanoma is supported by biologic evidence that
damage caused by ultraviolet radiation, particularly damage to
DNA, plays a central part in the pathogenesis of these tumors.
4) Age plays a major part in vulnerability to
photocarcinogenesis. Aging (the passage of time) provides more
opportunities for the initiation of tumor formation (the
induction of mutations by exposure to UV radiation) and for the
promotion of tumor formation (the reparative cell proliferation
after exposure to UV radiation or after other skin injury). There
is an age-associated decrease in the capacity to repair DNA, and
a consequent increase in the rate of mutations of DNA. Moreover,
the rate of removal of UV-radiation-induced DNA photoproducts
from UV-irradiated skin decreases with age, especially during the
first two decades of life.
5) There has been considerable research addressing the
relative contributions of UV-B wavelengths (290-320 nm) and UV-A
wavelengths (320-400 nm) to photocarcinogenesis, particularly to
the development of melanoma. UV-B radiation is overwhelmingly
responsible for the formation of the principle DNA lesions,
cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone
photoproducts, whose incorrect repair leads to mutations.
However, UV-A radiation is far more abundant in sunlight than UV-
B radiation, and UV-A radiation causes oxidative DNA damage that
is also potentially mutagenic. UV-A radiation is also believed to
contribute substantially to immunosuppression, thus preventing
immunologic rejection of nascent UV-induced skin cancers.
6) Unlike the more common skin cancers, which are associated
with total cumulative exposure to UV radiation, melanomas are
associated with intense intermittent exposure. Thus, basal-cell
and squamous-cell carcinomas occur most commonly in maximally
solar-exposed areas of the body (e.g., face, back of hands,
forearms, and in persons with almost daily and substantial
lifetime exposure to UV radiation, such as farmers and sailors).
In contrast, melanoma occurs most commonly in areas of the body
exposed to the Sun intermittently, such as the back in men and
the lower legs in women, with relative sparing of more frequently
exposed sites such as the face, hands, and forearms. Melanoma is
most common in persons with predominantly indoor occupations
whose exposure to the Sun is limited to weekends and vacations.
Indeed the large increase in the incidence of melanoma in recent
decades has been attributed in part to the ability of large
numbers of people to travel long distances to obtain intense
exposure to the Sun in winter.
7) The authors propose a hypothesis to explain the
epidemiology of melanoma as compared with non-melanoma skin
cancer, the authors suggesting that the data predict that a high-
dose first exposure to the Sun after a prolonged period of Sun
avoidance will cause substantial damage to DNA in *melanocytes
and *keratinocytes, both of which at that time have a relatively
low base-line capacity for DNA repair and a low melanin content.
The authors propose that the final effect of UV radiation is not
attributable simply to the cumulative dose -- the arithmetic sum
of all individual exposures over a lifetime -- but rather may be
strongly influenced by the dose per exposure and by the pattern
of exposures.
8) The authors conclude: "Protection from the Sun is
critical to the prevention of both melanoma and non-melanoma skin
cancers, and protection is most effective when it is begun in
early childhood. It is especially important to protect against
intermittent Sun exposures, in order to reduce genomic damage at
a time of maximal cellular vulnerability and to reduce the risk
of melanoma."
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New Engl. J. Med. 1999 340:1341
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Notes:
... ... *basal-cell: A basal cell is a cell of the deepest layer
of stratified epithelium. In animals, including humans,
epithelial cells (epithelium) compose the cell layers that form
the interface between a tissue and the external environment, for
example, the cells of the skin, the lining of the intestinal
tract, and the lung airway passages. The term "stratified
epithelium" is a general term for epithelium composed of several
layers of different cell types.
... ... *squamous-cell: The cells of the epithelium are for the
most part closely packed cells with little extracellular material
between adjacent cells, the cells arranged in continuous sheets
in either single or multiple layers. The cells may be flat,
cubelike, columnar, or a combination of shapes, and "squamous"
cells are flattened and scalelike.
... ... *carcinomas: In general, a carcinoma is any malignancy
derived from epithelial tissue.
... ... *melanoma: Melanomas are a group of skin cancers
involving *melanocytes, cells found throughout the lower layers
of the skin.
... ... *melanocytes: (melanodendrocytes) Pigment-producing cells
located in the deepest (basal) layer of the skin (epidermis) with
branching processes by means of which melanin-containing bodies
(melanosomes) are transferred to epidermal cells with a resultant
pigmentation of the epidermis.
... ... *keratinocytes: "Keratinocyte" is a generic term for any
mammalian epithelial cell that produces keratin, a group of
proteins present in cuticular structures (e.g., hair, nails).
----------
Related Background:
ALARM AT INCREASED INCIDENCE OF MELANOMA CANCERS
Melanocytes, cells which synthesize inclusions of the dark
pigment melanin, are found in the skin, choroid of the eye, and
hair. Melanocyte cancers are called melanomas, and if they are of
the rapidly proliferating type, and not caught early, they have a
high fatality rate. At the present time, the incidence of
melanoma in the U.S. is increasing faster than any other cancer,
and the statistics seem incredible: 0.0007 in 1935, 0.004 in
1977, 0.01 in 1997. According to projections, in the U.S. this
year, 40,300 new cases will be diagnosed, and 7,300 people will
die from the disease. The majority of oncologists and
epidemiologists believe this striking increase in incidence is
real and not a function of ambiguous diagnostic techniques. They
point to the simple fact that deaths from melanoma have increased
along with the incidence, even though early diagnosis and
improved treatment methods have increased the 5-year survival
rate. The projected U.S. incidence of melanoma in the year 2000
is 0.013, which means at that time 1 in 75 people will expect to
be diagnosed with the disease.
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New York Times 6 Aug 97
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21. ON QUARANTINE FOLLOWING BIOTERRORISM IN THE US
J. Barbera et al (George Washington University, US) discuss
bioterrorism in the US, the authors making the following points:
1) Concern for potential bioterrorist attacks causing mass
casualties has increased recently. Particular attention has been
paid to scenarios in which a biological agent capable of person-
to-person transmission, an agent such as smallpox, is
intentionally released among civilians. Multiple public health
interventions are possible to effect disease containment in this
context.
2) One disease control measure that has been regularly
proposed in various settings is the imposition of large-scale or
geographic quarantine on the potentially exposed population.
Although large-scale quarantine has not been implemented in
recent US history, it has been used on a small scale in
biological hoaxes, and it has been invoked in federally sponsored
bioterrorism exercises.
3) The authors review the scientific principles that are
relevant to the likely effectiveness of quarantine, the logistic
barriers to its implementation, legal-issues that a large-scale
quarantine raises, and possible adverse consequences that might
result from quarantine action.
4) The authors suggest that imposition of large-scale
quarantine -- compulsory sequestration of groups of possibly
exposed persons or human confinement within certain geographic
areas to prevent spread of contagious disease -- should not be
considered a primary public health strategy in most imaginable
circumstances. The authors suggest that in the majority of
contexts, other and less extreme public health actions are likely
to be more effective and create fewer unintended adverse
consequences than quarantine.
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J. Am. Med. Assoc. 2001 286:2711
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22. ADAPTATION OF CROPS TO ARID CONDITIONS
Y. Saranga et al (Hebrew University of Jerusalem, IL) discuss
crop adaptation, the authors making the following points:
1) Approximately one-third of the world's arable land
suffers from chronically inadequate supplies of water for
agriculture, and in virtually all agricultural regions, yields of
rain-fed crops are periodically reduced by drought. Global
climatic trends may accentuate this problem. Efficient irrigation
technologies help to reduce the gap between potential and actual
yield, but because of diminishing fresh water supplies in many
regions, genetic improvement of crop productivity under arid
conditions is necessary as a sustainable and economically viable
solution to this problem.
2) In practice, the genetic development of drought-tolerant
crops has been hindered by low heritability of endpoint
measurements such as yield and by lack of knowledge of more
precise physiological parameters that reflect genetic potential
for improved productivity under water deficit.
3) Water loss from a plant (transpiration) is an unavoidable
consequence of photosynthesis, whereby the energy of solar
radiation is used for carbon fixation. Carbon enters the leaves
of plants as carbon dioxide, diffusing through epidermal pores
(stomata), which also permit water vapor to diffuse out. Although
increased transpiration reduces water use efficiency (defined as
the ratio between dry matter production and water consumption at
the whole-plant level or as the ration between rates of carbon
dioxide fixation and transpiration at the leaf level), increased
transpiration also is a benefit in dissipating excess heat. Water
stress and heat stress almost invariably co-occur under arid-
region field conditions, and the resulting need for a balance
between tolerance of heat and drought complicates strategies for
manipulating plant water use to improve crop productivity under
arid conditions.
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Genome Research 2001 11:1988
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23. ON GENOMICS AND NEUROLOGY
Roger N. Rosenberg (University of Texas, US) discusses genomics
and neurology, the author making the following points:
1) Both groups that recently sequenced the human genome
reported that the number of protein-encoding genes in the human
genome is approximately 30,000, far less than previously
predicted. DNA was sequenced from 5 individuals: 3 males and 2
females, including 1 African-American, 1 Asian, 1 Hispanic, and 2
whites. Both sequencing groups found that the human genomes
sequenced were 99.9 percent genetically identical, with only 0.1
percent of the genome showing polymorphisms.
2) This high degree of interpersonal similarity in the human
genome is explainable by a "founder hypothesis". When,
approximately 40,000 years ago, Homo sapiens moved out of Africa
(where the species first evolved approximately 250,000 years ago)
into the Middle East and then into Europe and then Asia, a
founder group of approximately 10,000 of our genetic ancestors
undertook the migration, and 7000 generations later here we are.
This is not much time for many genetic mutations to occur and
accumulate. The human "neurogenome", the total number of genes
functionally expressed in the human nervous system, must be
similarly highly invariate from person to person.
3) Previous orientation in clinical and molecular
neurogenetics has been to ascribe function to a single gene and
the immediate biochemical and molecular consequence of a genetic
mutation causal of neurological disease. Now the emphasis has
shifted to consider the consequences of the expression of every
single gene in the nervous system to the genome in its totality.
Complex diseases involving multiple genes interacting with
environmental stimuli can be analyzed for quantitative and
coordinate levels of gene expression, and the information and
technical ability are now available to make these measurements.
Furthermore, the genomic consequence of a single gene's mutation
causal of neurological disease must be considered -- its overall
effect on all genes expressed in the nervous system. A genomic
analysis is now possible and necessary in measuring the genetic
expression of any single gene.
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J. Am. Med. Assoc. 2001 286:2869
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24. ON THE GLOBAL DIABETES EPIDEMIC
P. Zimmet et al (International Diabetes Institute, AU) discuss
global diabetes, the authors making the following points:
1) Diabetes mellitus, long considered a disease of minor
significance to world health, is now taking its place as one of
the main threats to human health in the 21st century. The past
two decades have seen an explosive increase in the number of
people diagnosed with diabetes worldwide. Pronounced changes in
the human environment, and in human behavior and lifestyle, have
accompanied globalization, and these have resulted in escalating
rates of both obesity and diabetes.
2) There are two main forms of diabetes: a) Type 1 diabetes
is due primarily to autoimmune-mediated destruction of pancreatic
beta-cell islets, resulting in absolute insulin deficiency.
People with type 1 diabetes must take exogenous insulin for
survival to prevent the development of ketoacidosis. The
frequency of type 1 diabetes is low relative to type 2 diabetes:
type 2 diabetes accounts for over 90 percent of cases globally.
b) Type 2 diabetes is characterized by insulin resistance and/or
abnormal insulin secretion, either of which may predominate.
People with type 2 diabetes are not dependent on exogenous
insulin, but may require it for control of blood glucose levels
if this is not achieved with diet alone or with oral hypoglycemic
agents.
3) The diabetes epidemic relates particularly to type 2
diabetes, and is occurring both in developed and developing
nations. Paradoxically, part of the problem relates to the
achievements in public health during the 20th century, with
people living longer owing to elimination of many of the
communicable diseases. Non-communicable diseases such as diabetes
and cardiovascular disease have now become the main public health
challenge for the 21st century. The global figure of people with
diabetes is set to rise from the current estimate of 150 million
to 220 million in 2010, and to 300 million in 2025. Most cases
will be of type 2 diabetes, which is strongly associated with a
sedentary lifestyle and obesity.
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Nature 2001 414:782
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25. IN FOCUS: ON BACTERIAL PLASMIDS
"Bacteria, like all living beings, must be able to cope with and
even adapt to changing environments in order to survive. The
traits encoded by genes in the DNA of their single chromosome are
often not enough to ensure their survival in the face of adverse
conditions. Therefore, bacteria, through evolution, have acquired
and maintained supplemental genetic information in the form of
accessory pieces of DNA that are separate from the chromosome
itself. These so-called "plasmids" exist as independent, self-
duplicating genetic elements -- like minichromosomes -- carrying
as few as 3 and as many as 300 different additional genes.
Anywhere from 1 to as many as 1000 copies of a plasmid may exist
in a cell. Many different plasmids can reside in the same cell.
The information that the plasmids carry enables bacteria to
perform new functions and engender new products that are not part
of their chromosomal genetic repertoires. The traits borne by
plasmids are numerous and versatile. They enable bacteria to
adhere to the cells lining the human gastrointestinal tract so
that these bacteria can withstand the continuous flow of food
residues passing through it. They help their host bacterium
survive a sudden change in the environment, such as extremes of
temperature. Unlike the physical and physiological changes that
occur in trees and plants with seasons, or that occur in animals
that hibernate during winter, these plasmid-borne 'survival'
traits are there to be called into play at any time... But
perhaps the most important function of plasmids in the bacteria
that we confront today is their ability to help their bacterial
hosts thwart the action of antibiotics.
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Stuart B. Levy: _The Antibiotic Paradox: How the Misuse of
Antibiotics Destroys Their Curative Powers_
(Perseue Publishing, Cambridge MA 2002, p.72)
http://www.amazon.com/exec/obidos/ASIN/0738204404/scienceweek
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26. FROM THE SW ARCHIVE:
FOUNDATIONS: 1932 -- THE YEAR OF PHYSICS
Identification of important discoveries in science is easier in
the long-run than in the short-term, principally because
consequences and influences of a discovery accumulate over
decades, and the most important discoveries acquire obvious
accumulations. The 20th century has been a phenomenal time for
physics, with important discoveries made nearly every year. In an
essay, H.G.B. Casimir (b. 1909), whose career in physics spans
almost the entire 20th century, chooses 1932 as an "annus
mirabilis" in physics. Casimir identifies four major discoveries
by physicists in 1932: the neutron, heavy hydrogen, nuclear
reactions, and the positron. But heavy hydrogen, in fact, was
discovered by a chemist, Harold C. Urey (1893-1981), who never
called himself other than a chemist, and who received the Nobel
Prize for Chemistry in 1934 for his discovery. Casimir implies
that the discovery of heavy hydrogen (and the "deuteron" nucleus)
followed easily from the discovery of the neutron by James
Chadwick (1891-1974), but Urey actually made his discovery of
heavy hydrogen in late 1931, before the results of Chadwick's
famous experiment were obtained. Leaving aside these historical
refinements, we note the following points made by Casimir:
1) Ernest Rutherford (1871-1937) postulated the existence of
the neutron, a particle without electric charge and approximately
the same mass as the proton. The neutron was discovered in 1932
by James Chadwick, who created beams of neutrons by irradiating
beryllium with alpha particles. The result of this experiment was
that it quickly became clear that atomic nuclei were composed of
protons and neutrons, and were not a medley of protons, "nuclear
electrons", alpha particles, etc., the medley that was considered
the consensus model of the atomic nucleus between 1920 and 1932.
The Chadwick experiment was indeed a major breakthrough in atomic
physics. Chadwick received the Nobel Prize for Physics in 1935.
2) Casimir says only the following about the discovery of
heavy hydrogen: "[After Chadwick's experiment] nuclei were
henceforth regarded as compounds of protons and neutrons. The
simplest case is one proton and one neutron. This particle was
called deuteron, D. Its oxide, D(sub2)O is the molecule of heavy
water. It was found in 1932 that about one part in six thousand
of normal water is heavy water." [Editor's note: Strangely,
Casimir does not mention Urey at all. Urey's discovery of heavy
hydrogen is a classic illustration of how a simple experiment can
yield extraordinarily important results. Urey began working on
heavy hydrogen in 1931, when it was already suspected by chemists
that hydrogen had a heavy isotope. Reasoning that liquid hydrogen
composed of the lighter hydrogen should evaporate before liquid
hydrogen composed of the more massive heavy hydrogen, Urey slowly
evaporated 4 liters of liquid hydrogen down to 1 cubic centimeter
and then investigated the spectrum of the remnant. He found the
ordinary absorption lines of hydrogen were accompanied by faint
lines in the exact positions later predicted by theory for heavy
hydrogen. The name "deuterium" was given to the heavy isotope.
After Urey's discovery, Chadwick and others in his laboratory
investigated the structure of the deuteron and demonstrated that
it consisted of one proton and one neutron.]
3) In 1932, John Cockcroft (1897-1967) and Ernest Walton
(1903-1995) used a 700-kilovolt high-voltage generator to
accelerate protons against lithium atoms and demonstrate that
these lithium atoms "broke in two". Cockcroft and Walton
announced they had "split the atom", and "so began the era of big
machines." Casimer states: "The high voltage generators were
succeeded by cyclotrons, the cyclotrons by even more powerful
apparatus." Cockcroft and Walton received the Nobel Prize for
Physics in 1951. [Editor's note: Here again, Casimir's account
requires some modification: The first "cyclotron" was built and
used experimentally and named in 1930 by Ernest O. Lawrence
(1901-1958), well before the Cockcroft-Walton experiment. Larger
and larger cyclotrons were indeed built during the following
decades. Concerning the "splitting of atoms", an argument can be
made that Rutherford had already done so before 1920. Rutherford
had certainly driven protons out of nitrogen atoms by bombarding
the atoms with alpha particles.]
4) In 1932, Carl D. Anderson (1905-1991) discovered the
positron, whose existence was predicted by the theoretical
physicist Paul A.M. Dirac (1902-1984). The positron is the
antiparticle of the electron. It has a charge identical but
opposite to that of the electron, and a rest mass identical to
that of the electron. Anderson received the Nobel Prize for
Physics in 1936. Casimir points out that the positron was the
first short-lived particle to be "created out of empty space" --
a prelude to the high-energy physics that blossomed beginning in
1950, and the powerful machines that now reveal the existence of
"whole families of short-lived particles, many of them predicted
by theory." Casimir concludes: "Sometimes it almost appears that
the theories are not a description of a nearly inaccessible
reality, but that so-called reality is a result of the theory."
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Nature 1999 402:463
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In the text, the affiliation following the names of authors in
sources with more than one author is the affiliation of the lead
author.
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