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ScienceWeek
SCIENCEWEEK
ScienceWeek November 8, 2002 Vol. 6 Number 45
An Online Research Digest Published Weekly Since 1997
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There ain't no rules around here! We're trying to accomplish
something! -- Thomas Edison (1847-1931)
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Section 1
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1. On Quantum Dots
The size, shape, and composition of quantum dots can all be
tailored to create a variety of desired properties, and these
"artificial atoms" can, in turn, be positioned and assembled
into complexes that serve as new materials.
2. History of Physics: On Dirac, Jordan, and Quantum Theory
In the autumn of 1925, Paul Dirac, a Cambridge University
graduate student of very few words, astonished the world of
physics with a remarkable paper on quantum mechanics. His
publication heralded the arrival of a mind of exceptional
originality and power at the frontier of physics.
3. On Microtubules and Mitosis
During the past several decades, our basic understanding of the
mechanisms underlying mitotic spindle function has advanced
significantly as a result of the discovery and characterization
of numerous proteins that bind spindle microtubules.
4. Electric Fields and Cell Division
Controlling cell division is fundamental. One environmental cue
that exerts profound control over both the orientation and
frequency of cell division in vivo is a naturally occurring,
wound-induced electric field.
5. On Microgel Release of Proteins
Hydrogels and microgels have been intensely investigated as
protein delivery vehicles because of their excellent
biocompatibility and hydrophilicity. A new acid-labile acetal
cross-linker has been synthesized and used to prepare
protein-loaded hydrogels and microgels.
6. On Locked-In Colloidal Transport
Depending on the balance of forces, a particle driven across a
corrugated potential energy landscape either flows with the
driving force or else becomes locked-in to a symmetry-preferred
route through the landscape. But despite their ubiquity,
kinetically locked-in states and transitions among them have
been observed directly only in numerical simulations.
7. On Brain-Volume Abnormalities in Children and Adolescents
with Attention-Deficit/Hyperactivity Disorder
Developmental trajectories for all structures, except caudate,
remain roughly parallel for patients and controls during
childhood and adolescence, suggesting that genetic and/or early
environmental influences on brain development in ADHD are fixed,
nonprogressive, and unrelated to stimulant treatment.
8. Fatigue, Sleep Deprivation, and the Performance of Clinicians
In the US, medical professionals, especially residents, are
working far beyond the limits that society deems acceptable in
other sectors. This practice is incompatible with a safe,
high-quality health care system.
9. ScienceWeek Notices and Subscription Information
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Section 2
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1. ON QUANTUM DOTS
D. Gammon and D.G. Steel (Naval Research Laboratory, US) discuss
quantum dots, the authors making the following points:
1) Atomic physics progressed rapidly at the beginning of the
last century, thanks, in large part, to optical spectroscopy.
Quantization and spin were discovered through optical studies,
as were other fundamental atomic properties. With the advent of
the laser, physicists learned how to manipulate atomic
wavefunctions by applying coherent optical fields.More
discoveries followed. Now, at the beginning of the new century,
optical techniques are being used to explore a new scientific
frontier: the atomlike entities known as "quantum dots" (QDs).
2) Measuring 1-100 nm across, QDs are semiconductor structures
in which the electron wavefunction is confined in all three
dimensions by the potential energy barriers that form the QD's
boundaries.(1) A QD's electronic response, like that of a single
atom, is manifest in its discrete energy spectrum, which appears
when electron-hole pairs are excited. Although the wavefunction
of a QD electron, and its corresponding hole, extends over many
thousands of lattice atoms, the pair -- termed an "exciton" --
behaves in a quantized and coherent fashion. The coherence is
relatively easy to detect and control optically -- for two
reasons. First, the superposition of the ground and excited
states dephases more slowly in QDs than in higher-dimensional
semiconductor structures. Second, QDs have large dipole moments
(50-100 times larger than those of atoms). Thanks to these
advantages, it is possible to probe and manipulate the
wavefunction of a single QD.(2)
3) QDs possess another attractive property. Their size, shape,
and composition can all be tailored to create a variety of
desired properties. These "artificial atoms" can, in turn, be
positioned and assembled into complexes that serve as new
materials. Researchers who work on QDs anticipate that a host of
complex, customized QD-based materials will become available.
Many types of QD materials have already been developed. Among
them are QDs formed by electrostatic gates. Researchers study
these QDs with far-infrared spectroscopy and with transport
techniques, such as conductance measurements. Great advances
have been made with electrostatic QDs, but this type of QD does
not interact strongly with light because the electrostatic gates
separate the electrons and holes, severely reducing the QD's
dipole moment. Fortunately, some types of QDs do interact
strongly with light and are being studied in detail, even at the
single QD level.(3-5)
References (abridged):
1. D. Bimberg, M. Grundmann, N. N. Ledentsov, Quantum Dot
Heterostructures, Wiley, Chichester, UK (1999).
2. N. H. Bonadeo et al.. Science 282, 1473 (1998).
3. J. Lumin. 70, L. E. Brus,A. L. Efros, T. Itoh, eds. (1996).
4. M. Bayer et al., Nature 405, 923 (2000).
5. D. V. Regelman et al., Phys. Rev. B 64, 165301 (2001).
Physics Today 2002 October
Related Background:
A TUNABLE KONDO EFFECT IN QUANTUM DOTS
Quantum dots are small electrically conducting regions,
typically less than 1 micron in diameter, that contain from one
to a few thousand electrons. Because of the small volume, the
electron energies within the dot are quantized, and the behavior
of the quantum dot is intermediate between that of an atom and
that of a classical macroscopic object. Such intermediate
systems are called "mesoscopic" systems, and in the past several
years great attention has been devoted to the physics of such
systems, since they apparently can provide insights into quantum
systems in general. The electronic states in quantum dots can be
probed by transport when a small *tunnel coupling is allowed
between the dot and nearby source and drain leads.
Cronenwett et al (3 authors at 2 installations, NL US) report
the realization of a tunable *Kondo effect in small quantum
dots, with the capability of switching a dot from a Kondo system
to non-Kondo system as the number of electrons on the dot is
changed from odd to even. The *Kondo temperature can be tuned by
means of a gate voltage as a single-particle energy state nears
the *Fermi energy. Measurements of the temperature and magnetic
field dependence of a *Coulomb-blockaded dot show good agreement
with prediction of both equilibrium and nonequilibrium Kondo
effects.
Science 24 Jul 98 281:540
Related Background:
QUANTUM DOTS
It is now possible to create extremely small crystals which
contain less than 1000 atoms, each crystal measuring a few
millionths of a millimeter across and thus in the nanoscale
domain. Certain of these nano-crystals, those of cadmium
selenide, for example, have peculiar attributes: crystals of
exactly the same composition but of different size exhibit quite
different properties, with the large nano-crystals of cadmium
selenide red in color, smaller crystals orange, and the smallest
(containing barely 100 atoms) yellow in color. The differences
in properties are due to quantum mechanical effects. These
extremely small atomic arrays are called "quantum dots", and
there is a current consensus that if quantum dots could be
integrated onto a chip, their unique electrical properties could
be harnessed to perform a function similar to a conventional
transistor, while requiring only a small fraction of the space.
In consequence, the creation of an appropriate regular array of
quantum dots would allow a computer processor many times more
powerful than any current supercomputer to be constructed on
single chip.
F. Remacle and R.D. Levine (2 installations, BE IL) present a
theoretical discussion of assemblies of metallic quantum dots
with each dot considered as an "atom". The dots are taken as
being packed close enough to be interacting. The authors suggest
that the key point is that such dots are essentially "designer"
atoms, since their electronic properties can be controlled via
the synthetic method used to prepare the dots. Of direct
significance are the size of the dot and the nature of the
ligands used to prevent coalescence of the dots. The energy
required to remove or add an electron to the dot is determined
by the size of the dot. The ligands control how closely the dots
can be packed and hence the strength of the coupling between
adjacent dots. An important parameter is the energy cost of
adding an electron to a dot: because of the large size of the
dots, the Coulomb repulsion of the added electron is low. Unlike
most ordinary atoms, quantum dots have a high capacity for
accommodating an additional electron.
Proc. Nat. Acad. Sci. 2000 97:553
Related Background:
LOCALIZATION-DELOCALIZATION IN QUANTUM DOTS
N.B. Zhitenev et al (US) report a study of the electron
localization-delocalization transition in quantum dots. The
problem of electron localization has remained a prime focus of
experiment and theoretical research over the past 40 years.
Single-electron capacitance spectroscopy precisely measures the
energies required to add individual electrons to a quantum dot.
The spatial extent of electronic wave functions was probed by
investigating the dependence of these energies on changes in the
dot confining potential. For low electron densities, electrons
occupy distinct spatial sites localized within the dot. At
higher densities, the electrons become delocalized, and all wave
functions are spread over the full dot area. Near the
delocalization transition, the last remaining localized states
exist at the perimeter of the dot. Unexpectedly, these electrons
appear to bind with electrons in the dot center.
Science 1999 285:715
Related Background:
MICROWAVE SPECTROSCOPY OF A QUANTUM DOT MOLECULE
Quantum dots are small conductive regions in a semiconductor,
the regions containing a variable number of electrons (from 1 to
1000) that occupy well-defined, discrete quantum states -- for
which reason they are often referred to as "artificial atoms".
Connecting quantum dots to current and voltage contacts allows
the discrete energy spectra of the system to be probed by
charge-transport measurements. Two quantum dots can be connected
to form an "artificial molecule", and depending on the strength
of the inter-dot coupling (which supports *quantum-mechanical
tunneling of electrons between the dots), the two dots can form
"ionic" or "covalent" bonds. In the ionic bond case, the
electrons are localized on individual dots, and in the covalent
bond case, the electrons are delocalized over both dots.
T.H. Oosterkamp et al now report a transition from ionic bonding
to covalent bonding in a quantum-dot "artificial molecule"
probed by microwave excitations. The authors suggest their
results demonstrate controllable *quantum coherence in
single-electron devices, an essential requirement for practical
applications of quantum-dot circuitry in the construction of
quantum computers.
Nature 1998 395:873
Text Notes:
... ... *quantum-mechanical tunneling: "Tunneling" is a quantum
mechanical phenomenon involving an effective penetration of an
energy barrier resulting from the width of the barrier being
less than the wavelength of the particle.
... ... *quantum coherence: In order for a system to be used to
process and transfer information, the system must be "coherent"
in its parts. In quantum physics, coherence is matter of locking
of phase differences between wave functions. The wave functions
of two or more particles are said to be coherent if the phase
difference between their wave functions remains constant. So if
new quantum electrodynamic information processing devices are to
be developed, methods must be found to keep the quantum states
of the parts of the system coherent long enough for information
to be processed and transferred from one place to another.
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2. HISTORY OF PHYSICS: ON DIRAC, JORDAN, AND QUANTUM THEORY
Kurt Gottfried (Cornell University, US) discusses quantum
electrodynamics, the author making the following points:
1) 1) In the autumn of 1925, Paul Adrien Maurice Dirac
(1902-1984), a Cambridge University graduate student of very few
words, astonished the world of physics with a remarkable paper
on quantum mechanics. His publication heralded the arrival of a
mind of exceptional originality and power at the frontier of
physics. The discovery by Werner Heisenberg (1901-1976) of
quantum mechanics sprang from the fertile soil of Goettingen and
Copenhagen, not Cambridge. Nevertheless, Dirac, knowing only
Heisenberg's ground-breaking but rather mysterious and
fragmentary paper, produced an almost complete formulation of
quantum mechanics wholly on his own, mirroring the achievement
of the experienced Goettingen collaboration of Max Born
(1882-1970), Pascual Jordan (1902-1980) and Heisenberg. Born
recalled this as "one of the greatest surprises of my scientific
life, for the name of Dirac was completely unknown to me".
2) Dirac, born 100 years ago this year, often displayed an
uncanny ability, whenever the need arose, to invent deep
mathematical concepts that were new to physicists. Readers of
his early paper would ask by what magic had he turned his
austere, abstract constructs into quantitative descriptions of
physical phenomena. Dirac's genius was quickly recognized -- he
was the youngest participant in the elite Solvay Congress of
1927, at which Niels Bohr and Albert Einstein began their long
debate about the foundations of quantum mechanics. On first
meeting him there, the formidable Wolfgang Pauli (1900-1958)
quipped that Dirac believed "there is no God, and Dirac is His
prophet".
3) The development of nonrelativistic quantum mechanics -- the
microscopic counterpart of newtonian mechanics -- was
essentially complete by the end of 1926. But it was not known
how to extend the new theory to the electromagnetic field, or to
particles moving with velocities approaching the speed of light.
Dirac solved both problems, giving birth to quantum
electrodynamics. Although Dirac's "quantization" of classical
electrodynamics yielded no great surprise, it was the first
consistent and correct account of the absorption, emission and
scattering of light. Ultimately, all the optical phenomena with
which we are so familiar are fully described by Dirac's
radiation theory of 1927.
References:
1. Schweber, S. S. QED and the Men Who Made It (Princeton Univ.
Press, 1994).
2. Kragh, H. Dirac: A Scientific Biography (Cambridge Univ.
Press, 1990).
3. Miller, A. I. Early Quantum Electrodynamics (Cambridge Univ.
Press, 1994).
Nature 2002 419:117
Related Background:
ON ONE HUNDRED YEARS OF QUANTUM PHYSICS
After 100 years of development, quantum physics is no longer
just a field, it is the bedrock of all of modern physics, and it
will be the origin, during the next 100 years, of new knowledge
and new applications not yet imaginable.
D. Kleppner and R. Jackiw (Massachusetts Institute of
Technology, US) present a review of the first century of quantum
physics, the authors making the following points:
1) Although quantum mechanics was created to describe an
abstract atomic world far removed from daily experience, its
impact on our daily lives could hardly be greater. The
spectacular advances in chemistry, biology, and medicine -- and
in essentially every other science -- could not have occurred
without the tools that quantum mechanics made possible. Without
quantum mechanics there would be no global economy to speak of,
because the electronics revolution that brought us the computer
age is a child of quantum mechanics. So is the photonics
revolution that brought us the Information Age. The creation of
quantum physics has transformed the world, bringing with it all
the benefits -- and the risks -- of a scientific revolution.
2) The principal players in the creation of quantum theory were
young. In 1925, Wolfgang Pauli was 25 years old, Werner
Heisenberg and Enrico Fermi were 24 years old, Paul Dirac and
Pascual Jordan were 23 years old. Erwin Schroedinger, at age 36,
was a late bloomer. Max Born and Niels Bohr were older still,
and it is significant that their contributions were largely
interpretive. The profoundly radical nature of the intellectual
achievement is revealed by Einstein's reaction. Having invented
some of the key concepts that led to quantum theory, Einstein
rejected it. His paper on Bose-Einstein statistics was his last
contribution to quantum physics and his last significant
contribution to physics. That a new generation of physicists was
needed to create quantum mechanics is hardly surprising. Lord
Kelvin described why in a letter to Niels Bohr congratulating
Bohr on his 1913 paper proposing the planetary model of the
atom. Kelvin said there was much truth in Bohr's paper, but he
would never understand it himself. Kelvin recognized that
radically new physics would need to come from unfettered minds.
3) The unique situation of quantum theory, this crucial yet
elusive theory, is perhaps best summarized by the following
observation: Quantum theory is the most precisely tested and
most successful theory in the history of science. Nevertheless,
not only was quantum mechanics deeply disturbing to its
founders, today -- 75 years after the theory was essentially
cast in its current form -- some of the luminaries of science
remain dissatisfied with its foundations and its
interpretations, even as they acknowledge its stunning power.
Science 2000 289:893
Related Background:
ON CHANGES IN THE DOING AND LEARNING OF QUANTUM PHYSICS
"Our understanding of atomic physics, of what we call the
quantum theory of atomic systems, had its origins at the turn of
the century and its great synthesis and resolutions in the
1920s. It was a heroic time. It was not the doing of any one
man; it involved the collaboration of scores of scientists from
many different lands, though from first to last the deeply
creative and subtle and critical spirit of Niels Bohr guided,
restrained, deepened, and finally transmuted the enterprise. It
was a period of patient work in the laboratory, of crucial
experiments and daring action, of many false starts and many
untenable conjectures. It was a time of earnest correspondence
and hurried conferences, of debate, criticism, and brilliant
mathematical improvisations... When quantum theory was first
taught in the universities and institutes, it was taught by
those who had participated, or had been engaged spectators, in
its discovery. Some of the excitement and wonder of the
discoverer was in their teaching; now, after two or three
decades, it is taught not by the creators but by those who have
learned from others who have learned from those creators. It is
taught not as history, not as a great adventure in human
understanding, but as a piece of knowledge, as a set of
techniques, as a scientific discipline to be used by the student
in understanding and exploring new phenomena in the vast work of
the advance of science, or its application to invention and to
practical ends. It has become not a subject of curiosity and an
object of study but an instrument of the scientist to be taken
for granted by him, to be used by him, to be taught to him as a
mode of action, as we teach our children to spell and to add."
J. Robert Oppenheimer: _Science and the Common Understanding_
(Simon & Schuster, New York 1953)
Related Background:
THEORETICAL PHYSICS: ON PASCUAL JORDAN AND NAZI PHYSICS
The individual human brain is an extremely complex natural
system, and the individual human mind, the manifestation of the
dynamics of that system, is at least of an equal order of
complexity and also a domain where paradox is commonplace.
(Ernst) Pascual Jordan (1902-1980) was one of the great
theoretical physicists of this century, the principal architect
of the Born-Heisenberg-Jordan matrix quantum mechanics (see Note
#1 below), the essential inventor of *quantum field theory, and
a 20th century tour de force in mathematical physics -- but he
was also an ardent Nazi storm trooper, "complete with brown
uniform, jackboots, and swastika armband..." And if that paradox
is not enough, add to it the fact that Jordan not only defended
the physics of Albert Einstein to the Nazi regime which despised
Einstein because Einstein was a Jew, but also devoted
considerable effort to developing the details of Einstein's
general theory of relativity.
Engelbert L. Schucking (New York University, US), theoretical
physicist and a former student of Pascual Jordan (beginning in
1952), presents a biographical essay on Jordan, with Schucking
making the following points:
1) Pascual Jordan was the originator of the quantum theory of
fields, "which we now take to be the basis of all physics." He
was the first to realize that all things in the Universe
--photons, electrons, protons, atoms, and elephants -- are field
quanta. Of the triumvirate Pascual Jordan, *Max Born, and
*Werner Heisenberg that formulated matrix quantum mechanics in
1925, Jordan was the principal architect of the theory. But in
spite of his revolutionary contributions, Jordan never achieved
the acclaim of his colleagues Heisenberg and *Wolfgang Pauli,
perhaps because Jordan was looked down upon by Pauli and
Heisenberg as more of a mathematician than a physicist.
2) Schucking points out that Jordan also made the first
formulation of what is now called *Fermi-Dirac statistics. The
story is that in 1925 Max Born, who was then editor of the
_Zeitschrift fur Physik_ was given a paper by Jordan for
publication in the journal. Born put the paper in his briefcase
and then left for the US to give lectures at MIT. Born forgot
about the paper, and when he returned to Germany six months
later, he found the paper at the bottom of the suitcase.
According to Max Born: "It contained what came to be known as
the Fermi-Dirac statistics. In the meantime, it had been
discovered by Enrico Fermi and, independently, by Paul Dirac.
But Jordan was the first."
3) In May 1933, Jordan joined the Nazi party. But even before
the Nazis came to power in January 1933, Jordan had been a
conservative nationalist, and under the pseudonym "Domeier" he
had published his elitist views in the right-wing journal
_Deutsches Volkstum_ (_German Heritage_). In November 1933,
Jordan joined an SA (Sturmabteilung) unit and became a storm
trooper. He volunteered for the Luftwaffe in 1939, worked mostly
as a meteorologist at airfields, and also at the notorious
Peenemunde rocket center. In 1953, thanks to the intercession of
Wolfgang Pauli, Jordan was "rehabilitated" and advanced from
visiting to full professor at the University of Hamburg.
4) The Schucking article includes an amusing extract from a play
by *Bertolt Brecht (_Fright and Misery in the Third Reich_) in
which Brecht satirizes Nazi physics in a scene in which two
physicists execute tortuous verbalizations in an attempt to
avoid mentioning the dangerous "E-word" (Einstein). In fact,
most German physicists, when writing about relativity during the
Nazi era, shunned the dangerous E-word. Schucking notes: "A
circumspect Heisenberg managed to avoid it." Jordan, however,
did use Einstein's name when writing about relativity.
5) Schucking notes that the contributions of Pascual Jordan are
for the most part still widely unknown. "The bulk of the
monumental 1925 Born-Jordan paper 'Zur Quantenmechanik' was
written by Jordan [*Note #1]." It has also been argued that
Jordan's habilitation lecture was crucial for Heisenberg's
discovery of the uncertainty principle. "Even Jordan's
pioneering work in quantum field theory was not immediately
appreciated. His formalism of *creation and annihilation
operators, now the basic language of physics, was still viewed
with suspicion by Pauli in 1933." In a seminal paper in 1935,
Jordan showed how his formalism could treat the physics of
multiparticle systems -- now the standard treatment in condensed
matter physics -- and generate the representations that are now
used in particle physics.
6) In 1979, *Eugene Wigner proposed Jordan for the Nobel Prize
in Physics, but the Swedish Academy awarded the prize that year
to *Sheldon Glashow, Abdus Salam, and Steven Weinberg
--according to Schucking, "three practitioners of the art that
Jordan had invented." Less than a year later, Jordan died at the
age of 78 while filling in formulae in a manuscript at his
kitchen table.
[Editor's note: The 1997 edition of _Chambers Biographical
Dictionary_ contains a short paragraph on "(Ernst) Pascual
Jordan (1902- ) German theoretical physicist". Evidently, 17
years after Jordan's death, the editors of the dictionary were
not aware of it. Several current popular biographical
dictionaries of scientists contain no mention of Pascual Jordan
at all. David Bohm's 1951 textbook _Quantum Theory_ does not
mention Jordan at all. The 1958 4th edition of Paul Dirac's _The
Principles of Quantum Mechanics_ does not mention Jordan at all.
Jordan is also not mentioned anywhere in Richard Feynman's
_Lectures on Physics_ (1965). Additional note: Pascual Jordan
(1902-1980) should not be confused with the noted mathematician
Camille Jordan (1838-1922). Camille Jordan was the foremost
specialist in algebra of his time, publishing research in
topology, analysis, and particularly in group theory. The
so-called "Jordan curve" in analysis is the curve of Camille
Jordan.]
Physics Today October 1999
Text Notes:
... ... *quantum field theory: The mathematical fusion of
quantum mechanics with special relativity theory. It is now the
overall theory of fundamental particles and their interactions,
with each type of particle represented by appropriate operators
which obey specific algebraic commutation laws.
... ... *Max Born: (1882-1970) Nobel Prize in Physics 1954. Born
did fundamental work in quantum theory, particularly work
linking the wave function of the electron to electron
distribution probability. It was Born who apparently coined the
term "quantum mechanics". Heisenberg was one of Born's students.
... ... *Werner Heisenberg: (1901-1976) Nobel Prize in Physics
1932. Developed quantum theory (matrix quantum mechanics) and
formulated the uncertainty principle, which concerns matter,
radiation, and their reactions, and which places absolute limits
on the achievable accuracy of measurement of physical phenomena
in the quantum domain.
... ... *Wolfgang Pauli: (1900-1958) Nobel Prize in Physics
1945. Originated the exclusion principle, which states that in a
given system no two fermions (electrons, protons, neutrons, or
other elementary particles of half-integral spin) can be
characterized by the same set of quantum numbers. He also
predicted the existence of neutrinos.
... ... *Fermi-Dirac statistics: The statistics of an assembly
of identical half-integer spin particles. Such particles satisfy
the Pauli exclusion principle, i.e., no two particles of the
same kind in the system may simultaneously occupy the same
quantum state.
... ... *Bertolt Brecht: (1898-1956) Considered by many to be
Germany's greatest dramatist, Brecht presented his plays as
instruments of sociological analysis. When Hitler came to power
in 1933, Brecht left Germany and in 1941 finally settled in
Hollywood (US). The play in question, _Fright and Misery under
the Third Reich_, is also called _Fear and Loathing under the
Third Reich_ (Furcht und Elend des dritten Reiches, 1945). In
1948, Brecht moved to East Berlin to direct a theater. Always in
conflict with bureaucratic authority, Brecht's years in East
Germany proved difficult for both himself and the East German
government.
... ... *Note #1: What is known as "Heisenberg's matrix
mechanics" (matrix quantum mechanics) is a particular
formulation of quantum mechanics in which the vector aspect of
quantum theory is emphasized, whereas the wave aspects of
quantum phenomena play a secondary role. Although wave quantum
mechanics (subsequently developed by Schroedinger, see below)
and matrix quantum mechanics appear superficially to be very
different, the two theories are in fact completely equivalent
and lead to the same physical predictions. Werner Heisenberg's
first paper on the subject appeared in 1925, and in this paper
matrix theory is not mentioned explicitly because Heisenberg did
not realize yet that his mathematical operations had a matrix
theory interpretation. The connection with matrix theory was
demonstrated the same year in the already mentioned important
paper by Max Born and Pascual Jordan (Z. fur Physik 1925
34:858). In a second paper a short time later, Born and Jordan
and Heisenberg all published together and clarified the
principles of matrix quantum mechanics (Z. fur Physik 1926
35:557). The wave quantum mechanics of Erwin Schroedinger was
not published until 1926 (Annalen der Physik 1926 79:361), so
that historically matrix mechanics was invented and developed
before Schroedinger invented wave mechanics. Given wave
mechanics, the invention of matrix mechanics might be viewed as
inevitable, since the set of all solutions of a linear
differential equation can be regarded as a vector space. The
fact that matrix mechanics was invented _without_ wave mechanics
is considered by some physicists to be an astounding theoretical
accomplishment.
... ... *creation and annihilation operators: These are quantum
mechanical operators which increase or reduce, respectively, the
occupation of a single quantum state by one. For example, an
annihilation operator applied to a state of one particle yields
the vacuum. In this context, "operators" are abstract
representations of certain specific mathematical operations, and
consideration of the various algebras of such operators has
proved to be of immense importance in theoretical physics.
... ... *Eugene Wigner: (1902-1995) He introduced the idea of
parity, or symmetry theory, into nuclear physics. He shared the
1963 Nobel Prize for Physics with Maria Goeppert-Mayer
(1906-1972) and Hans Jensen (1907-1973).
... ... *Sheldon Glashow, Abdus Salam, and Steven Weinberg:
Shared the 1979 Nobel Prize in Physics for the unified theory of
weak and electromagnetic fundamental forces, and for the
prediction of the existence of the weak neutral current. Abdus
Salam (1926-1996).
ScienceWeek http://www.scienceweek.com
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3. ON MICROTUBULES AND MITOSIS
David J. Sharp (Albert Einstein College of Medicine, US)
discusses mitosis, the author making the following points:
1) The segregation of chromosomes during mitosis occurs on a
remarkably complex and dynamic microtubule-based machine termed
the "mitotic spindle". During the past several decades, our
basic understanding of the mechanisms underlying spindle
function has advanced significantly as a result of the discovery
and characterization of numerous proteins that bind spindle
microtubules. Most of these can be categorized into two
multi-family classes: motor proteins, which generate force and
movement along the surface of microtubules, and "conventional"
microtubule-associated proteins (MAPs) [1], many of which are
thought to stabilize microtubules. While motors are now known to
participate in numerous mitotic events [2], the mitotic
functions of MAPs remain far more mysterious. New and surprising
insights into the spectrum of mitotic MAP functions have emerged
from a series of studies of MAST/Orbit, the Drosophila member of
a phylogenetically conserved MAP family [3–5]. Most recently,
work by Maiato et al [5] has implicated MAST/Orbit as a key
player in maintaining spindle architecture and moving
chromosomes along spindle microtubules. And a new study [6] of
the yeast MAST/Orbit homologue STU1p has revealed unexpected
functional interrelationships between members of this MAP family
and mitotic motors.
2) MAPs were originally discovered as proteins that co-purify
with microtubules from bovine brain, and so early on they were
considered primarily for their roles in organizing neuronal
microtubule arrays. Subsequently, related proteins were
identified in a variety of non-neuronal systems, and it quickly
became clear that their functions extend beyond the nervous
system and even into mitosis. To date, multiple MAPs with
potential roles in mitosis have been discovered, most falling
into one of several conserved families. One of these is defined
by MAST/Orbit, originally identified in two independent genetic
screens for mitotic regulators in Drosophila. Homologues of
MAST/Orbit have also been identified in fungi, nematodes, and
humans. Upon analysis, the mast/orbit locus of Drosophila was
found to encode an approximately 165 kDa microtubule-binding
protein that localizes to centrosomes, spindle microtubules and
kinetochores (multiprotein structures which link chromosomes to
spindle microtubules). Loss-of-function mutations in mast/orbit
were found to result in striking defects in spindle structure,
most significantly the presence of mono-astral spindles
associated with circular arrangements of mitotic chromosomes
[3,4]. Thus, it was clear that MAST/Orbit impacts the structural
integrity of the spindle.
References (abridged):
1. Mandelkow E. and Mandelkow E.M. (1995) Microtubules and
microtubule-associated proteins. Curr. Opin. Cell Biol., 7:72-81.
2. Hoyt M.A. and Geiser J.R. (1996) Genetic analysis of the
mitotic spindle. Annu. Rev. Genet., 30:7-33.
3. Inoue Y.H., do Carmo Avides M., Shiraki M., Deak P.,
Yamaguchi M., Nishimoto Y., Matsukage A. and Glover D.M. (2000)
Orbit, a novel microtubule-associated protein essential for
mitosis in Drosophila melanogaster. J. Cell Biol., 149:153-166.
4. Lemos C.L., Sampaio P., Maiato H., Costa M., Omel'yanchuk
L.V., Liberal V. and Sunkel C.E. (2000) Mast, a conserved
microtubule-associated protein required for bipolar mitotic
spindle organization. EMBO J., 19:3668-3682.
5. Maiato H., Sampaio P., Lemos C.L., Findlay J., Carmena M.,
Earnshaw W.C. and Sunkel C.E. (2002) MAST/Orbit has a role in
microtubule-kinetochore attachment and is essential for
chromosome alignment and maintenance of spindle bipolarity. J.
Cell Biol., 157:749-760.
Current Biology 2002 12:R585
Related Background Brief:
GENETIC ANALYSIS OF THE MITOTIC SPINDLE. Much of our
understanding of the molecular basis of mitotic spindle function
has been achieved within the past decade. Studies utilizing
genetically tractable organisms have made important
contributions to this field and these studies form the basis of
this review. The authors focus upon three areas of spindle
research: spindle poles, centromeres, and spindle motors. The
structure and duplication mechanisms of spindle poles are
considered as well as their roles in organizing spindle
microtubules. Centromeres vary considerably in their size and
complexity. The authors describe recent progress in our
understanding of the relatively simple centromeres of the yeast
Saccharomyces cerevisiae and the complex centromeres that are
more typical of eukaryotic cells. Microtubule-based motor
proteins that generate the characteristic spindle movements have
been identified in recent years and can be grouped into families
defined by conserved primary sequence and mitotic function. M.A.
Hoyt and J.R. Geiser: Annu Rev Genet 1996 30:7.
Related Background Brief:
ORBIT, A NOVEL MICROTUBULE-ASSOCIATED PROTEIN ESSENTIAL FOR
MITOSIS IN DROSOPHILA MELANOGASTER. The authors describe a
Drosophila gene, "orbit", that encodes a conserved 165-kD
microtubule-associated protein (MAP) with GTP binding motifs.
Hypomorphic mutations in orbit lead to a maternal effect
resulting in branched and bent mitotic spindles in the syncytial
embryo. In the larval central nervous system, such mutants have
an elevated mitotic index with some mitotic cells showing an
increase in ploidy. Amorphic alleles show late lethality and
greater frequencies of hyperploid mitotic cells. The presence of
cells in the hypomorphic mutant in which the chromosomes can be
arranged, either in a circular metaphase or an anaphase-like
configuration on monopolar spindles, suggests that polyploidy
arises through spindle and chromosome segregation defects rather
than defects in cytokinesis. A role for the Orbit protein in
regulating microtubule behavior in mitosis is suggested by its
association with microtubules throughout the spindle at all
mitotic stages, by its copurification with microtubules from
embryonic extracts, and by the finding that the Orbit protein
directly binds to MAP-free microtubules in a GTP-dependent
manner. Y.H. Inoue et al: J Cell Biol. 2000 149:5.
Related Background Brief:
MAST, A CONSERVED MICROTUBULE-ASSOCIATED PROTEIN REQUIRED FOR
BIPOLAR MITOTIC SPINDLE ORGANIZATION. Through mutational
analysis in Drosophila, the authors report they have identified
the gene "multiple asters" ("mast"), which encodes a new 165 kDa
protein. mast mutant neuroblasts are highly polyploid and show
severe mitotic abnormalities including the formation of mono-
and multi-polar spindles organized by an irregular number of
microtubule-organizing centers of abnormal size and shape. The
mast gene product is evolutionarily conserved since homologues
were identified from yeast to man, revealing a novel protein
family. Antibodies against Mast and analysis of tissue culture
cells expressing an enhanced green fluorescent protein-Mast
fusion protein demonstrate that during mitosis, this protein
localizes to centrosomes, the mitotic spindle, centromeres and
spindle midzone. Microtubule-binding assays indicate that Mast
is a microtubule-associated protein displaying strong affinity
for polymerized microtubules. The defects observed in the mutant
alleles and the intracellular localization of the protein
suggest that Mast plays an essential role in centrosome
separation and organization of the bipolar mitotic spindle. C.L.
Lemos et al: EMBO J 2000 19:3668.
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4. ELECTRIC FIELDS AND CELL DIVISION
B. Song et al (University of Aberdeen, UK) discuss cell
division, the authors making the following points:
1) Cell division and migration are fundamental in development,
wound healing, and pathology. Many cell types undergo oriented
cell division and directed migration, and understanding the
controls of these behaviors is crucial. In the Drosophila
central nervous system (CNS), neuroepithelial cells delaminate
basally from the neuroectoderm and divide asymmetrically along
the apical-basal axis, producing for each cell a neuroblast and
a ganglion mother cell. The neuroblast remains adjacent to the
neuroectoderm and retains stem cell-like properties, whereas the
ganglion mother cell divides once more to produce differentiated
neurons or glia (1,2). Cortical neurons in the mouse CNS also
are generated from asymmetric divisions (3). Cells in the
germinal layers lining the ventricles can divide with a vertical
cleavage plane and remain in the germinal layer, or divide
horizontally, generating one germinal cell and a daughter cell,
which will migrate away and differentiate into a neuron. A
variety of proteins become distributed asymmetrically during
these cell divisions and play crucial roles in determining the
extent of symmetry and the orientation of cell division (see 4
and 5). Oriented division and directional migration are
essential for correctly locating postmitotic neurons in the
developing nervous system.
2) Several environmental cues contribute to oriented cell
division and directional migration. Appropriate cell-cell
contact directs the orientation of mitotic spindles, whereas
chemotaxis modulates the direction of cell migration. Naturally
occurring electric fields (EFs) also orient division and direct
cell migration. For example, corneal epithelial cells in culture
migrate toward a cathode in a physiological EF and divide with a
cleavage plane perpendicular to the EF vector. Endogenous EFs
exist in many situations where cells divide and migrate.
Disrupting the endogenous EFs associated with the neural plate
and neural tube in amphibia causes specific abnormalities of CNS
development. Similarly, the cellular events underpinning wound
healing depend on the wound-induced EF. If this is inhibited,
healing is compromised. Perhaps disruptions arise because EFs
control cell division, cell proliferation, and cell migration in
vivo, in a manner similar to that demonstrated directly in vitro.
3) In summary: Controlling cell division is fundamental. One
environmental cue that exerts profound control over both the
orientation and frequency of cell division in vivo is a
naturally occurring, wound-induced electric field (EF). Wounds
in rat corneas generate endogenous EFs in the plane of the
epithelial sheet because the transcorneal potential difference
(TCPD; +40 mV internally positive) collapses at the wound edge,
but is maintained at normal levels at 0.5 mm back from the
wound. The authors report they manipulated the endogenous EF
this creates by using drugs with differing actions. The
wound-induced EF controlled the orientation of cell division;
most epithelial cells divided with a cleavage plane parallel to
the wound edge and perpendicular to the EF vector. Increasing or
decreasing the EF pharmacologically, respectively increased or
decreased the extent of oriented cell division. In addition,
cells closest to the wound edge, where the EF was highest, were
oriented most strongly by the EF. Remarkably, an endogenous EF
also enhanced the frequency of cell division. This also was
regulated by enhancing or suppressing the EF pharmacologically.
Because the endogenous EF also regulated the wound healing rate,
it may act as one control of the interplay between cell
migration and cell division during healing.
References (abridged):
1. Giansanti, M. G. , Gatti, M. & Bonaccorsi, S. (2001)
Development (Cambridge, U.K.) 128, 1137-1145.
2. Lu, B. , Roegiers, F. , Jan, L. Y. & Jan, Y. N. (2001)
Nature 409, 522-525.
3. Chenn, A. & McConnell, S. K. (1995) Cell 82, 631-641.
4. Zhao, M. , Pu, J. , Forrester, J. V. & McCaig, C. D. (2002)
FASEB J. 16, 857-859.
5. Bienz, M. (2001) Nat. Cell Biol. 3, E67-E68.
Proc. Nat. Acad. Sci. 2002 99:13577
Related Background Brief:
ADHERENS JUNCTIONS INHIBIT ASYMMETRIC DIVISION IN THE DROSOPHILA
EPITHELIUM. Asymmetric division is a fundamental mechanism for
generating cellular diversity. In the central nervous system of
Drosophila, neural progenitor cells called neuroblasts undergo
asymmetric division along the apical-basal cellular axis.
Neuroblasts originate from neuroepithelial cells, which are
polarized along the apical-basal axis and divide symmetrically
along the planar axis. The asymmetry of neuroblasts might arise
from neuroblast-specific expression of the proteins required for
asymmetric division. Alternatively, both neuroblasts and
neuroepithelial cells could be capable of dividing
asymmetrically, but in neuroepithelial cells other polarity cues
might prevent asymmetric division. The authors demonstrate that
by disrupting adherens junctions one can convert the symmetric
epithelial division into asymmetric division. The authors
further confirm that the adenomatous polyposis coli (APC) tumor
suppressor protein is recruited to adherens junctions, and
demonstrate that both APC and microtubule-associated EB1
homologues are required for the symmetric epithelial division
along the planar axis. The authors suggest their results
indicate that neuroepithelial cells have all the necessary
components to execute asymmetric division, but that this pathway
is normally overridden by the planar polarity cue provided by
adherens junctions. B. Lu et al: Nature 2001 409:522.
Related Background Brief:
MEMBRANE LIPIDS, EGF RECEPTORS, AND INTRACELLULAR SIGNALS
COLOCALIZE AND ARE POLARIZED IN EPITHELIAL CELLS MOVING
DIRECTIONALLY IN A PHYSIOLOGICAL ELECTRIC FIELD. Directed cell
migration is essential for tissue formation, inflammation, and
wound healing. Chemotaxis plays a major role in these situations
and is underpinned by asymmetric intracellular signaling.
Endogenous electric fields (EFs) are common where cell movement
occurs, such as in wound healing, and cells respond to electric
field gradients by reorienting and migrating directionally
(galvanotaxis/electrotaxis). The authors demonstrate that a
physiological EF redistributed both EGF (epidermal growth
factor) receptors and detergent-insoluble membrane lipids
asymmetrically, leading to cathodal polarization and enhanced
activation of the MAP kinase, ERK1/2. This induced leading-edge
actin polymerization in directionally migrating mammalian
epithelial cells. Inhibiting the EGF receptor-MAP kinase
signaling pathway significantly decreased leading edge actin
asymmetry and directional migration. The authors propose a model
in which EF-polarized membrane lipid domains and EGF receptors
cause asymmetric signaling through MAP kinase, which drives
directional cell migration. A comparison is made with the
mechanisms underpinning chemotaxis. M. Zhao et al: FASEB Journal
Express 2002 10.1096/fj.01-0811fje.
Related Background Brief:
CELL CONTACTS ORIENT SOME CELL DIVISION AXES IN THE
CAENORHABDITIS ELEGANS EMBRYO. Cells of the early Caenorhabditis
elegans embryo divide in an invariant pattern. The author
demonstrates that the division axes of some early cells (EMS and
E) are controlled by specific cell-cell contacts (EMS-P2 or E-P3
contact). Altering the orientation of contact between these
cells alters the axis along which the mitotic spindle is
established, and hence the orientation of cell division.
Contact-dependent mitotic spindle orientation appears to work by
establishing a site of the type described by Hyman and White
(1987. J. Cell Biol. 105:2123-2135) in the cortex of the
responding cell: one centrosome moves toward the site of
cell-cell contact during centrosome rotation in both intact
embryos and reoriented cell pairs. The effect is especially
apparent when two donor cells are placed on one side of the
responding cell: both centrosomes are "captured", pulling the
nucleus to one side of the cell. No centrosome rotation occurs
in the absence of cell-cell contact, nor in nocodazole-treated
cell pairs. The results suggest that some of the cortical sites
described by Hyman and White are established cell autonomously
(in P1, P2, and P3), and some are established by cell-cell
contact (in EMS and E). Additional evidence presented suggests
that in the EMS cell, contact-dependent spindle orientation
ensures a cleavage plane that will partition developmental
information, received by induction, to one of EMS's daughter
cells. B Goldstein: J Cell Biol 1995 129:1071.
Related Background Brief:
SPATIAL CONTROL OF ACTIN POLYMERIZATION DURING NEUTROPHIL
CHEMOTAXIS. Neutrophils respond to chemotactic stimuli by
increasing the nucleation and polymerization of actin filaments,
but the location and regulation of these processes are not well
understood. Using a permeabilized-cell assay, the authors
demonstrate that chemotactic stimuli cause neutrophils to
organize many discrete sites of actin polymerization, the
distribution of which is biased by external chemotactic
gradients. Furthermore, the Arp2/3 complex, which can nucleate
actin polymerization, dynamically redistributes to the region of
living neutrophils that receives maximal chemotactic
stimulation, and the least-extractable pool of the Arp2/3
complex co-localizes with sites of actin polymerization. The
authors suggest their observations indicate that
chemoattractant-stimulated neutrophils may establish discrete
foci of actin polymerization that are similar to those generated
at the posterior surface of the intracellular bacterium Listeria
monocytogenes. The authors propose that asymmetrical
establishment and/or maintenance of sites of actin
polymerization produces directional migration of neutrophils in
response to chemotactic gradients. O.D. Weiner et al: Nat Cell
Biol 1999 1:75.
Related Background Brief:
ELECTRIC FIELD-DIRECTED CELL MOTILITY INVOLVES UP-REGULATED
EXPRESSION AND ASYMMETRIC REDISTRIBUTION OF THE EPIDERMAL GROWTH
FACTOR RECEPTORS AND IS ENHANCED BY FIBRONECTIN AND LAMININ.
Wounding corneal epithelium establishes a laterally oriented, DC
electric field (EF). Corneal epithelial cells (CECs) cultured in
similar physiological EFs migrate cathodally, but this requires
serum growth factors. Migration depends also on the substrate.
On fibronectin (FN) or laminin (LAM) substrates in EFs, cells
migrated faster and more directly cathodally. This also was
serum dependent. Epidermal growth factor (EGF) restored
cathodal-directed migration in serum-free medium. Therefore, the
hypothesis that EGF is a serum constituent underlying both
field-directed migration and enhanced migration on ECM molecules
was tested. The authors used immunofluorescence, flow cytometry,
and confocal microscopy and report that 1) EF exposure
up-regulated the EGF receptor (EGFR); so also did growing cells
on substrates of FN or LAM; and 2) EGFRs and actin accumulated
in the cathodal-directed half of CECs, within 10 min in EF. The
cathodal asymmetry of EGFR and actin staining was correlated,
being most marked at the cell-substrate interface and showing
similar patterns of asymmetry at various levels through a cell.
At the cell-substrate interface, EGFRs and actin frequently
colocalized as interdigitated, punctate spots resembling tank
tracks. Cathodal accumulation of EGFR and actin did not occur in
the absence of serum but were restored by adding ligand to
serum-free medium. Inhibition of MAPK, one second messenger
engaged by EGF, significantly reduced EF-directed cell
migration. Transforming growth factor and fibroblast growth
factor also restored cathodal-directed cell migration in
serum-free medium. However, longer EF exposure was needed to
show clear asymmetric distribution of the receptors for
transforming growth factor and fibroblast growth factor. The
authors propose that up-regulated expression and redistribution
of EGFRs underlie cathodal-directed migration of CECs and
directed migration induced by EF on FN and LAM. M. Zhao et al:
Mol. Biol. of the Cell 1999 10:1259
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5. ON MICROGEL RELEASE OF PROTEINS
N. Murthy et al (University of California Berkeley, US) discuss
microgels as delivery vehicles, the authors making the following
points:
1) Hydrogels and microgels have been intensely investigated as
protein delivery vehicles because of their excellent
biocompatibility and hydrophilicity.(1) Numerous protein-loaded
hydrogels and microgels have been synthesized and investigated.
For example, hydrogels or microgels composed of acrylamide and
methylene bisacrylamide, dextrans grafted with methacrylates,
PEG-methacrylates, and PLGA-PEG-methacrylates have been
synthesized and used to encapsulate proteins.(2) These hydrogels
are usually cross-linked using ester, amide, or carbonate
linkages that are most susceptible to degradation via
base-catalyzed hydrolysis.
2) For drug delivery applications, it would be particularly
useful to develop protein-loaded hydrogels and microgels that
degrade by acid-catalyzed hydrolysis. There are numerous drug
delivery targets that exist at acidic pHs, such as tumors,
inflammatory tissues, and the phagolysosomes of antigen
presenting cells.(3) Acid-degradable hydrogels and microgels
designed to undergo degradation in these acidic tissues should
therefore be capable of selective delivery of their therapeutic
contents. At present, the only method available for engineering
acid sensitivity in hydrogels is through the incorporation of
cationic groups, which become protonated at acidic pHs and cause
hydrogel swelling.(4) However, for protein delivery, it would be
preferable to develop acid-sensitive hydrogels that were
neutral, thus avoiding the potential toxicity of polycations and
the complications of electrostatic interaction with proteins.(5)
3) In summary: The authors report that a new acid-labile acetal
cross-linker was synthesized and used to prepare protein-loaded
hydrogels and microgels. This cross-linker undergoes an
acid-catalyzed degradation with a half-life of 5.5 min at pH 5.0
and 24 h at pH 7.4. Protein-loaded hydrogels were synthesized
with this cross-linker, and their release profiles were measured
as a function of pH. Hydrogels made with the acetal cross-linker
release their contents in a pH-dependent manner. The acetal
cross-linker was also used to synthesize microgels with sizes
between 1 and 10 microns, a range suitable for phagocytosis. The
unique acid sensitivity of the acetal cross-linker should make
it a useful synthetic intermediate in the design of
acid-sensitive drug or gene delivery systems.
References (abridged):
1. Park, K.; Shalaby, W. S.; Park, H. Biodegradable Hydrogels
for Drug Delivery; Technomic Publishing Co.: Lancaster, PA, 1993.
2. (a) Ekman, B.; Lofter, C.; Sjoholm, I. Biochemistry 1976, 15,
5115-5120. (b) Sawhney, A.; Pathak, C.; Hubbell, J.
Macromolecules 1993, 26, 581-587. (c) Sanxia, L.; Anseth, K. S.
Macromolecules 2000, 33, 2509-2515. (d) Dijk-Wolthius, W. N. E.;
et al. Macromolecules 1997, 30, 4639-4645.
3. (a) Helmlinger, G.; Sckell, A.; Dellian, M.; Forbes, N. S.;
Rakesh, K. Jain. Clin. Cancer Res. 2002, 8, 1284-1291. (b)
Trevani, S.; Andonegui, G.; Giordano, M.; Lopez, D.; Gamberale,
R.; Minucci, F.; Geffner, J. R. J. Immunol. 1999, 162, 4849-57.
4. Park, T. G. Biomaterials 1999, 20, 517-521. Kim, I. Y.; et
al. J. Appl. Polym. Sci. 2002, 85, 2661-2666.
5. Sassi, A. P.; Shaw, A. J.; Han, S. M.; Blanch, H. W.;
Prausnitz, J. M. Polymer 1996, 11, 2151-2164.
J. Am. Chem. Soc. 2002 124:12398
Related Background Brief:
INCORPORATION OF MACROMOLECULES IN MICROPARTICLES: PREPARATION
AND CHARACTERISTICS. Macromolecules can easily be incorporated
in microparticles of polyacrylamide by copolymerization with
acrylamide in a water-in-oil emulsion. The microparticles
preferably arount 1-3 mum in diameter, will have a macroporous
structure formed by the polymeric network. The amount of
incorporation of the macromolecules will depend on the structure
of the network, which, in turn, will depend on the total amount
of monomer (T) and the relative amount of cross-linking agent
(C) in the monomeric solution. Two mechanisms are responsible
for the incorporation; all macromolecules are, independently of
the size, fixed in the threads of polyacrylamide and large ones
are entrapped within the network formed by the threads. The
amount entrapped will depend on the size of the macromolecule
and the mean pore radius of the gel. In microparticles with a
total concentration of monomers of 8% and a cross-linking of 25%
(T-C=8-25) the biological properties of incorporated
macromolecules are retained, due to the macroporous structure,
as found in binding studies with albumin. The density of the
particles will also depend on C and T and, to some extent, on
the protein concentration. Due to the fixation in the
polyacrylamide threads, some of the incorporated macromolecules
will be exposed on the surface, allowing them to react with, for
instance, cells, which cannot penetrate the particles. The
optimal conditions for the incorporation of macromolecules in
the microparticles are investigated. B. Ekman et al:
Biochemistry 1976 15:5115.
Related Background Brief:
BIOERODIBLE HYDROGELS BASED ON PHOTOPOLYMERIZED POLY(ETHYLENE
GLYCOL)-CO-POLY(A-HYDROXY ACID) DIACRYLATE MACROMERS. The
authors report that macromers having a poly(ethylene glycol)
central block, extended with oligomers of a-hydroxy acids such
as oligo(dl-lactic acid) or oligo(glycolic acid) and terminated
with acrylate groups, were synthesized and characterized with
the goal of obtaining a biodegradable hydrogel that could be
formed in direct contact with tissues or proteins by
photopolymerization of aqueous solutions of the macromer. It was
determined that the PEG component of these macromers must be
greater than approximately 55 mol% to provide water solubility.
The amphiphilic nature of the macromers causes them to assume a
micellar conformation, which enables them to undergo rapid
photopolymerization. Due to the multifunctionality of the
macromers, polymerization results in the formation of
crosslinked gels. These gels degrade upon hydrolysis of the
oligo(a-hydroxy acid) regions into poly(ethylene glycol), the
a-hydroxy acid, and oligo(acrylic acid). The degradation rates
of these gels can be tailored by appropriate choice of the
oligo(a-hydroxy acid) from less than 1 day to up to 4 mo. Using
nontoxic photoinitiators, the macromers can be rapidly
photopolymerized with visible light in direct contact with
tissues without excess heating or local toxicity. If polymerized
in contact with tissues, the gels adhere to the tissues,
presumably by interpenetration; if polymerized prior to contact
with tissues, the gels are very nonadhesive, presumably by
possession of a large amount of free water which is not
hydrogen-bonded with the ether linkages of the ethylene glycol
mers. The authors suggest these novel materials are suitable for
a number of biomedical applications and show potential for use
in macromolecular drug delivery. A.S. Sawhney et al:
Macromolecules 1993 26:581.
Related Background Brief:
pH-RESPONSIVE POLYMER MICROSPHERES: RAPID RELEASE OF
ENCAPSULATED MATERIAL WITHIN THE RANGE OF INTRACELLULAR pH. The
authors report that microspheres formed from
4,4'-Trimethylenedipiperidine-butylene diacrylate copolymer (I)
release their encapsulated contents rapidly and quantitatively
in the range of intracellular pH values. The size distribution
of the spheres (4-6 microns) is considered suitable for delivery
to phagocytotic cells such as macrophages. The preliminary
evidence indicating the internalization and processing of I
microspheres by macrophages is presented. The double emulsion
process is feasible for the encapsulation of water-soluble
compounds using I. The size distributions of microspheres formed
from I correlated well with the distributions of
poly(lactic-co-glycolic acid) (PLGA) microspheres within 5-30
microns. The degradation of I at pH 7.4 was relatively slow and
85-90% of encapsulated material could be retained in the polymer
matrix for long periods of time at physiological pH values. Cell
membrane translocation and escape from acidic intracellular
vesicles represent substantial obstacles to efficient delivery
by endocytosis or phagocytosis. The particles formed from I
could be internalized by phagocytosis and particle rupture
occurred more readily inside the cell than for PLGA
microspheres. Thus, I can be used to encapsulate a water-soluble
polymer, retain the material at extracellular or cytoplasmic pH
values, and release the encapsulated contents in the range of
endosomal/lysosomal pH values. The authors suggest the
incorporation of degradable, pH-sensitive materials such as I
could be used in designing new DNA-based vaccine formulations
targeted to macrophages. D.M. Lynn et al: Angew Chem Int Ed 2001
40:1707.
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6. ON LOCKED-IN COLLOIDAL TRANSPORT
P.T. Korda et al (University of Chicago, US) discuss colloidal
transport, the authors making the following points:
1) Depending on the balance of forces, a particle driven across
a corrugated potential energy landscape either flows with the
driving force or else becomes locked-in to a symmetry-preferred
route through the landscape. The emergence of kinetically
locked-in states whose transport properties are invariant over a
range of control parameters characterizes many systems and is
referred to variously as phase-locking, mode-locking, and
stochastic resonance. Examples arise in the electromigration of
atoms on crystal surfaces [1], in flux creep through type-II
superconductors [2,3], in flux tunneling through Josephson
junction arrays [4], and in electron transport through charge
density waves and two-dimensional electron gases [5]. Related
problems abound in the theory of chemical kinetics and glass
formation.
2) Despite their ubiquity, kinetically locked-in states and
transitions among them have been observed directly only in
numerical simulations. Their presence in experiments has been
inferred indirectly from their influence on collective
large-scale properties such as the magnetoresistance and Hall
conductance of superconductors and two-dimensional electron
gases. Consequently, most theoretical studies have addressed the
collective transport properties of strongly coupled systems
whose internal interactions modify the influence of the
modulated potential and the external driving force. How kinetic
lock-in affects single-particle transport has received far less
attention.
3) The authors describe observations of a hierarchy of
kinetically locked-in states in the microscopic trajectories of
individual colloidal particles flowing classically through large
arrays of optical tweezers. Unlike previous studies on other
systems which have found that locked-in states correspond to
deterministically commensurate trajectories through the
potential energy landscape, the observations of the authors also
reveal a new class of statistically locked-in states. The
locked-in states' ability to systematically and selectively
deflect particle trajectories suggests that optical trap arrays
will be useful for continuously fractionating materials in
suspension.
References (abridged):
1. 0. Pierre-Louis and M.I. Haftel, Phys. Rev. Lett. 87, 048701
(2001)
2. C. Reichhardt and F. Nori, Phys. Rev. Lett. 82, 414 (1999)
3. M. Baert, V.V. Metlushko, R. Jonckheere, V.V. Moshchalkov,
and Y. Bruynseraede, Phys. Rev. Lett 74, 3269 (1995); K. Harada,
0. Kamimura, H. Kasai, T. Matsuda, A. Tonomura, and V.V.
Moshchalkov, Science 274, 1167 (1996); J.L Martin, M. Velez, J.
Nogues, and LK. Schuller, Phys. Rev. Lett 79, 1929 (1997); D.J.
Morgan and J. B. Ketterson, Phys. Rev. Lett 80, 3614 (1998)
4. K. D. Fisher, D. Stroud, and L. Janin, Phys. Rev B 60, 15371
(1999); V.I. Marconi and D. Dommguez, Phys. Rev. B 63, 174509
(2001)
5. J. Wiersig and K.-H. Ahn, Phys. Rev. Lett. 87, 026803 (2001)
Phys. Rev. Lett. 2002 89:128301
Related Background:
ON STOCHASTIC RESONANCE
A.A. Zaikin et al (Potsdam University, DE) discuss stochastic
resonance, the authors making the following points:
1) It has been established that dynamical noise, which usually
has a disordering impact, can be used to induce order in
nonlinear nonequilibrium systems under certain conditions.
Examples of this counterintuitive influence of random
fluctuations are noise-induced transitions, stochastic transport
in ratchets (also in a synthesis with a transition), or
noise-induced pattern formation. However, one of the most
significant examples is "stochastic resonance", which has been
experimentally observed in several physical and biological
systems.
2) In the classical situation, stochastic resonance consists of
an optimization by noise of the response of a bistable system to
a weak periodic signal. Besides this standard scenario,
stochastic resonance has also been found in monostable,
excitable, nondynamical systems, in systems without a threshold,
in systems without an external force (so-called "coherence
resonance"), and in systems with transient noise-induced
structure.
3) In addition, it has recently been demonstrated that the
energy of fluctuations can be used even more efficiently in
spatially extended systems by using noise twofold: to
synchronize output hops across a potential barrier with an
external signal, and also to optimally construct the barrier
itself. This phenomenon is known as "doubly stochastic
resonance" and occurs in systems of coupled overdamped
oscillators. It is a synthesis of two basic phenomena:
stochastic resonance and noise-induced phase transitions.
Another important and nontrivial phenomenon related to
stochastic resonance in spatially distributed systems is the
phenomenon of "noise enhanced propagation", in which the
propagation of a harmonic forcing through an unforced bistable
or excitable medium is increased for an optimal intensity of the
additive noise.
Phys. Rev. Lett. 2002 88:010601
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7. ON BRAIN-VOLUME ABNORMALITIES IN CHILDREN AND ADOLESCENTS
WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
F.X. Castellanos et al (New York University, US) discuss
attention deficit disorder, the authors making the following
points:
1) Attention-deficit/hyperactivity disorder (ADHD), the most
common childhood psychiatric disorder, is thought to reflect
subtle abnormalities in central nervous system functioning.(1)
For this reason, ADHD is being studied increasingly with a
variety of brain imaging techniques throughout the life span.
Magnetic resonance imaging (MRI) is particularly suitable for
the study of pediatric patients, providing high-resolution
images without ionizing radiation. Previous MRI neuroimaging
studies, most with small samples, have reported smaller anatomic
areas and/or volumes in patients with ADHD in regions of the
corpus callosum,(2-5) smaller volumes and/or hypoactivation of
prefrontal brain, basal ganglia, and cerebellum. However, a
recent study noted inconsistencies in the ADHD neuroimaging
literature and concluded that specific abnormalities have not
yet been convincingly demonstrated.
2) The authors report a study to compare regional brain volumes
at initial scan and their change over time in medicated and
previously unmedicated male and female patients with ADHD and
healthy controls. The case-control study was conducted from
1991-2001 at the National Institute of Mental Health, Bethesda,
Md, of 152 children and adolescents with ADHD (age range, 5-18
years) and 139 age- and sex-matched controls (age range, 4.5-19
years) recruited from the local community, who contributed 544
anatomic magnetic resonance images. Using completely automated
methods, the main outcome measures were initial volumes and
prospective age-related changes of total cerebrum, cerebellum,
gray and white matter for the 4 major lobes, and caudate nucleus
of the brain were compared in patients and controls.
3) Results: On initial scan, patients with ADHD had
significantly smaller brain volumes in all regions, even after
adjustment for significant covariates. This global difference
was reflected in smaller total cerebral volumes (-3.2%, adjusted
F1,280 = 8.30, P = .004) and in significantly smaller cerebellar
volumes (-3.5%, adjusted F1,280 = 12.29, P = .001). Compared
with controls, previously unmedicated children with ADHD
demonstrated significantly smaller total cerebral volumes
(overall F2,288 = 6.65; all pairwise comparisons Bonferroni
corrected, -5.8%; P = .002) and cerebellar volumes (-6.2%,
F2,288 = 8.97, P<.001). Unmedicated children with ADHD also
exhibited strikingly smaller total white matter volumes (F2,288
= 11.65) compared with controls (-10.7%, P<.001) and with
medicated children with ADHD (-8.9%, P<.001). Volumetric
abnormalities persisted with age in total and regional cerebral
measures (P = .002) and in the cerebellum (P = .003). Caudate
nucleus volumes were initially abnormal for patients with ADHD
(P = .05), but diagnostic differences disappeared as caudate
volumes decreased for patients and controls during adolescence.
Results were comparable for male and female patients on all
measures. Frontal and temporal gray matter, caudate, and
cerebellar volumes correlated significantly with parent- and
clinician-rated severity measures within the ADHD sample
(Pearson coefficients between -0.16 and -0.26; all P values were
<.05).
4) The authors conclude: Developmental trajectories for all
structures, except caudate, remain roughly parallel for patients
and controls during childhood and adolescence, suggesting that
genetic and/or early environmental influences on brain
development in ADHD are fixed, nonprogressive, and unrelated to
stimulant treatment.
References (abridged):
1. Tannock R. Attention deficit hyperactivity disorder: advances
in cognitive, neurobiological, and genetic research. J Child
Psychol Psychiatry. 1998;39:65-99.
2. Hynd GW, Semrud-Clikeman M, Lorys AR, et al. Corpus callosum
morphology in attention-deficit hyperactivity disorder:
Morphometric analysis of MRI. J Learn Disabil. 1991;24:141-146.
3. Giedd JN, Castellanos FX, Casey BJ, et al. Quantitative
morphology of the corpus callosum in attention deficit
hyperactivity disorder. Am J Psychiatry. 1994;151:665-669.
4. Semrud-Clikeman M, Filipek PA, Biederman J, et al.
Attention-deficit hyperactivity disorder: magnetic resonance
imaging morphometric analysis of the corpus callosum. J Am Acad
Child Adolesc Psychiatry. 1994;33:875-881.
5. Baumgardner TL, Singer HS, Denckla MB, et al. Corpus callosum
morphology in children with Tourette syndrome and attention
deficit hyperactivity disorder. Neurology. 1996;47:477-482.
J. Am. Med. Assoc. 2002 288:1740
Related Background Brief:
ATTENTION DEFICIT HYPERACTIVITY DISORDER: ADVANCES IN COGNITIVE,
NEUROBIOLOGICAL, AND GENETIC RESEARCH. Conceptual and
technological advances in cognitive neuroscience and molecular
genetics have the potential to identify the pathogenesis of
psychiatric disorders. The author reviews the application of
these technologies to the scientific study of attention deficit
hyperactivity disorder. The author begins with a summary of
shifts in conceptualization and scientific study of this common
condition. This is followed by a critical review of findings
from recent cognitive, neuroimaging, and genetic studies. The
available data do not yet permit an integration across these
different levels of enquiry, but implicate problems in response
inhibition, dysfunction of frontostriatal networks, and genetic
factors in the pathogenesis of this complex behavioral
phenotype. The review closes with suggestions for future
interdisciplinary research. R. Tannock: J Child Psychol
Psychiatry 1998 39:65.
Related Background Brief:
CORPUS CALLOSUM MORPHOLOGY IN ATTENTION DEFICIT-HYPERACTIVITY
DISORDER: MORPHOMETRIC ANALYSIS OF MRI. Although behavioral
evidence provides support for the notion that attention
deficit-hyperactivity disorder (ADHD) is related to central
nervous system dysfunction, there is little direct evidence to
reveal which neurometabolic systems or brain structures are
involved. Recent magnetic resonance imaging (MRI) studies
suggest that, compared to nondisabled controls, ADHD children
may have a smaller right frontal region. Morphometric analysis
of MRI scans was used in the present exploratory study to
determine whether correlated regional variation might exist in
the corpus callosum of children with ADHD. While all MRI scans
were judged to be clinically normal, morphometric analysis
revealed that, compared to nondisabled controls, ADHD children
had a smaller corpus callosum, particularly in the region of the
genu and splenium, and in the area just anterior to the
splenium. Interhemispheric fibers in these regions interconnect
the left and right frontal, occipital, parietal, and posterior
temporal regions. These results suggest that subtle differences
may exist in the brains of children with ADHD and that
deviations in normal corticogenesis may underlie the behavioral
manifestations of this disorder. G.W. Hynd et al: J Learn
Disabil 1991 24:141.
Related Background Brief:
QUANTITATIVE MORPHOLOGY OF THE CORPUS CALLOSUM IN ATTENTION
DEFICIT HYPERACTIVITY DISORDER. The authors report that by means
of quantitative neuroanatomic imaging they assessed the
hypothesis that there are structural brain abnormalities
relevant to frontal lobe circuitry in children with attention
deficit hyperactivity disorder (ADHD). The midsagittal
cross-sectional area of the corpus callosum, divided into seven
sections, was measured from magnetic resonance images of 18 boys
with ADHD and 18 carefully matched normal boys. Results: Two
anterior regions, the rostrum and the rostral body, were found
to have significantly smaller areas in the ADHD group. These
areas correlated in the expected direction with teacher and
parent ratings of hyperactivity/impulsivity. The authors
conclude: This finding supports theories of abnormal frontal
lobe development and function in ADHD. J.N. Giedd et al: Am J
Psychiatry 1994 151:665.
Related Background Brief:
ATTENTION-DEFICIT HYPERACTIVITY DISORDER: MAGNETIC RESONANCE
IMAGING MORPHOMETRIC ANALYSIS OF THE CORPUS CALLOSUM. The
authors report a study to document possible differences in
corpus callosal area and shape between children with
attention-deficit hyperactivity disorder (ADHD) and controls.
Fifteen carefully diagnosed right-handed male subjects with ADHD
with overactivity symptomatology were compared to 15
right-handed male control subjects. The corpus callosum was
divided into seven areas on the midsagittal slice of a magnetic
resonance image with shape analysis also conducted. Results: An
exploratory shape analysis showed no significant differences in
shape between the groups. No group differences were found in the
area, length, or anterior regions of the corpus callosum. The
ADHD subjects were found to have significantly smaller posterior
corpus callosum regions than the control group, with the
splenium accounting for most of the variance between the groups.
The authors conclude: The splenial area of the corpus callosum
is smaller in children with ADHD than in a sample of normally
developing children. These smaller areas may relate to commonly
seen sustained attention deficits which in turn negatively
impact on the development of more advanced levels of attention
such as self-regulation. Further study of the regions
surrounding the splenial area is suggested to determine whether
they are correlated in size to the smaller corpus callosum. M.
Semrud-Clikeman et al: J Am Acad Child Adolesc Psychiatry 1994
33:875.
Related Background Brief:
CORPUS CALLOSUM MORPHOLOGY IN CHILDREN WITH TOURETTE SYNDROME
AND ATTENTION DEFICIT HYPERACTIVITY DISORDER. The authors report
a study to investigate the morphology of the corpus callosum
(CC) in Tourette syndrome (TS) and attention deficit
hyperactivity disorder (ADHD) to determine whether these
conditions affect distinct regional differences. Seventy-seven
children and adolescents, aged 6 to 16 years, comprised the four
research groups -- 16 patients with TS, 21 patients with TS plus
ADHD, 13 patients with ADHD, and 27 unaffected control subjects.
A semiautomated, computer-assisted procedure was used to measure
the total area, five subregions, centerline length, perimeter,
and bending angle of the CC. MRI data were analyzed using
several statistical methods, primarily two-tailed analysis of
variance to test the effects of TS and ADHD status, while
controlling for the influence of age, gender, and total
intracranial area (an estimate of brain size). TS was associated
with significant increases in the area of four of five
subdivisions, the total area, and the perimeter of the CC. ADHD
was associated with a significant decrease in the area of the
rostral body. There were no interactions between TS and ADHD
factors. The authors suggest these findings indicate that the
area of the CC is larger in children with TS, and that this
difference is independent of age, handedness, intracranial area,
and the diagnosis of ADHD. The authors suggest their findings
support hypotheses that the neurobiologic mechanisms in TS and
ADHD involve frontal/subcortical circuits. T.L. Baumgardner et
al: Neurology 1996 47:477.
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8. FATIGUE, SLEEP DEPRIVATION, AND THE PERFORMANCE OF CLINICIANS
D.M. GABA and S.K. Howard (Stanford University, US) discuss
fatigue and sleep deprivation, the authors making the following
points:
1) Sleep deprivation due to extended work hours and circadian
disruption has long been a concern in medicine (1), and it has
been called the Achilles' heel of the medical profession.(2) The
levels of continuous duty and work hours for health care
personnel are much greater than those allowed in the
transportation and nuclear-power industries.(3,4) The problem is
most severe for residents in training but extends to experienced
physicians and nurses. Clinicians who have been deprived of
sleep are part of a health care system in trouble. A report from
the Institute of Medicine concludes that the system fails to
ensure that patients are safe or that the quality of care they
receive is high.(5) Kenneth Shine, former president of the
institute, stated, "We have nurses working 12-hour sessions back
to back; we have house officers working enormous hours. We would
never do that if we were designing a good system in terms of
quality of care."
2) The work and on-call hours of residents are disturbing to
them and to the media. Many trainees work more than 80 hours a
week, and 100-to-120-hour weeks are common. Regularly scheduled
on-call duty is often 24 to 36 hours long and is occasionally
even longer. If sleep is possible during on-call duty, it is
often limited and fragmented. Fatigue is a common complaint of
house staff, and many trainees (41 percent) say they have made
errors that they attribute to fatigue. In addition, there is
some evidence that house staff are at increased risk for motor
vehicle accidents attributable to fatigue.
3) There is a large body of laboratory data showing beyond a
doubt that fatigue impairs human performance. In fact, the
effect of sleep deprivation on a task that involves tracking has
been shown to be equivalent to the effect of alcohol
intoxication; in one study, performance of such a task after 24
hours of sustained wakefulness was equivalent to the performance
with a blood alcohol concentration of 0.10 percent. Studies of
simulated driving have had similar results.
4) The authors conclude: In the US, medical professionals,
especially residents, are working far beyond the limits that
society deems acceptable in other sectors. This practice is
incompatible with a safe, high-quality health care system. An
integrated program of measures to prevent excessive hours of
work and sleep deprivation should be adopted. Substantial reform
is possible within the current system of medical care. The steps
recently taken by the Accreditation Council for Graduate Medical
Education (ACGME) are promising but may not be sufficient, since
they contain various loopholes, do not go as far as they could,
and apply only to residents. The ACGME requirements are more
lenient than those imposed in other Western countries and in
other hazardous US industries. If the medical profession does
not implement meaningful changes for trainees and, eventually,
for experienced clinicians, they may ultimately be forced on
them.
References (abridged):
1. Friedman RC, Kornfeld DS, Bigger TJ. Psychological problems
associated with sleep deprivation in interns. J Med Educ
1973;48:436-441.
2. Leach DC. Residents' work hours: the Achilles heel of the
profession? Acad Med 2000;75:1156-1157.
3. Office of Technology Assessment. Biological rhythms:
implications for the worker. Washington, D.C.: Government
Printing Office, 1991. (Report No. OTA-BA-463.)
4. Petition to the Occupational Safety and Health Administration
requesting that limits be placed on hours worked by medical
residents (HRG publication #1570). Washington, D.C.: Public
Citizen Health Research Group, 2002. (Accessed September 24,
2002, at
http://www.citizen.org/publications/release.cfm?ID=6771.)
5. Kohn LT, Corrigan JM, Donaldson MS, eds. To err is human:
building a safer health system. Washington, D.C.: National
Academy Press, 2000.
New Engl. J. Med. 2002 347:1249
Related Background Brief:
HEALTH CARE QUALITY AND HOW TO ACHIEVE IT. Studies conducted by
the Institute of Medicine have demonstrated a serious gap
between what the American health care system provides and its
full potential. This results from a substantial amount of
overuse, underuse, and misuse of health care. An Institute of
Medicine (IOM) publication focusing attention on medical errors
-- To Err is Human: Building a Safer Healthcare System --
galvanized the public and private sector as well as the
professions to strive for building a safer health care system.
In its report, Crossing the Quality Chasm: A New Health System
for the 21st Century, the IOM's committee visualized a series of
aims and rules for the health care system that would propel it
successfully into the 21st century. Multidisciplinary
professional teams should provide care for an increasing portion
of the population (now about 40%) who have one or more chronic
illnesses. Since 20 conditions account for 80% of America's
health care costs, the author recommends that a special focus be
placed upon 15 of these conditions to systematically improve the
quality of care over the next five years. Information technology
offers important opportunities to improve patient safety and
contribute to better and continuous improvement of quality. The
elimination of written clinical notes by the year 2010 is an
achievable objective. These developments require medical
educators and health professionals to move from a 20th-century
paradigm of the physician who was in solo practice, held
autonomy as a central value, prided himself or herself upon
continuous learning and the acquisition of new knowledge, and
laid claim to infallibility when confronting patients and
colleagues. The 21st-century paradigm is that of physicians who
understand teamwork and systems of care in which they can
provide leadership. Group practice, both virtual and real, will
allow the support of information systems, the collection of
evidence about care, and efforts for continuous quality
improvement. Fallibility should be replaced by an approach to
multidisciplinary problem solving, and the acquisition of
knowledge must be associated with the commitment and
understanding of the need for change. Kenneth I. Shine: Academic
Medicine 2002 77:91.
Related Background Brief:
LEARNING, SATISFACTION, AND MISTREATMENT DURING MEDICAL
INTERNSHIP: A NATIONAL SURVEY OF WORKING CONDITIONS. Concerns
about the working and learning environment of residency training
continue to surface. Previous surveys of residents have focused
on work hours and income, but have shed little light on how
residents view their training experience. The authors report an
attempt to provide a description of the internship year as seen
by a large cross section of second-year residents. The study
involved a mail survey conducted in 1991 of residency programs
in the United States. The study involved a random 10% sample
(N=1773) of all second-year residents listed in the American
Medical Association's medical research and information database.
The main outcome measures were: What and who contributes most to
residents' learning during internships, degree of satisfaction
with the internship experience, on-call and sleep schedules,
incidents of perceived mistreatment or abuse, observations of
unethical behavior, and experiences of harassment or
discrimination. Results: A total of 1277 surveys (72%) of 1773
mailed were returned. Overall, respondents reported a moderate
level of satisfaction with their first year of residency. On a
scale of 0 to 3, residents rated other residents as contributing
most (score of 2.3) to their learning, with special patients
ranked second (2.1). During a typical work week, residents
reported that they spent an average of 56.9 hours on call in the
hospital. A total of 1185 (93%) residents reported experiencing
at least 1 incident of perceived mistreatment, with 53%
reporting being belittled or humiliated by more senior
residents. Among women residents, 63% reported having
experienced at least 1 episode of sexual harassment or
discrimination. A total of 45% of residents reported having
observed another individual falsifying medical records, and 70%
saw a colleague working in an impaired condition, most often
lack of sleep. Regression analyses suggest that satisfaction
with the residency experience was associated with the presence
of factors that enhanced learning, and fewer experiences of
perceived mistreatment. The authors conclude: Residents report
significant problems during their internship experience.
Satisfaction with internship is enhanced by positive learning
experiences and lack of mistreatment. S.R. Daugherty et al: J.
Am. Med. Assoc. 1998 279:1194.
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