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ScienceWeek
SCIENCE-WEEK
A Weekly Email Digest of the News of Science
A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.
August 3, 2001 -- Vol. 5 Number 31
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He who would do good to another must do it in
Minute Particulars: General Good is the plea
of the scoundrel, hypocrite and flatterer; for
Art and Science cannot exist but in minutely
organized Particulars.
-- William Blake (1757-1827)
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=-=-=-=-=-=-=-=-=
Section 1
=-=-=-=-=-=-=-=-=
Contents of this Issue (Full reports in Section 2):
1. IN BRIEF:
Snowball Earth
Carbon dioxide removal by forests
Chemical systems and phase space trajectories
Crystal structures of a biomolecular motor
Notch signaling and vasculogenesis
Bacterial pathogens and protein secretion
Schizophrenia genetics research
Ancient agriculture in Mexico
2. THEORETICAL PHYSICS: THE WEAKNESS OF GRAVITY
An understanding of the weakness of gravitation can be derived
from an understanding of the smallness of the mass of the proton,
and in particular from the constraints imposed by quantum
chromodynamics on the coupling constants between quarks.
3. THEORETICAL PHYSICS: ENTROPY AND TIME
Time is one of the great puzzles of physics and philosophy, the
most fundamental aspect of our experience. A fundamental problem
is to provide an explanation of the apparent directionality of
time. The classic explanation relating time to entropy leaves
many questions unanswered.
4. MEDICAL BIOLOGY: BRAIN DEATH
There is currently a widespread legal and societal acceptance
that death of a person is the total cessation of integrated brain
function, especially cessation of function of the brainstem. To a
considerable degree, this acceptance derives from the capacity of
ventilators to perpetuate cardiopulmonary function for a
considerable time despite failure of other organs.
5. PUBLIC HEALTH: CANCER EPIDEMIOLOGY
Many types of cancers vary in incidence by more than an order of
magnitude between different populations, and every type of cancer
is rare in some part of the world. The convergence towards local
cancer rates seen among immigrants excludes a genetic explanation
of these differences.
6. NEUROSCIENCE: NATURE OF HUMAN EMOTIONS
Charles Darwin (1809-1882) recognized that the process of
evolution by natural selection applied not only to anatomic
structures but also to the "mind" of an animal and to expressive
behavior, a conclusion that led him to write a treatise on
emotional expression (_The Expression of Emotion in Man and
Animals_, 1872).
7. IN FOCUS: ON SCIENCE AND CREATIVITY
It is not the need of the age which gives the individual
scientist his sense of pleasure and of adventure, and that
excitement which keeps him working late into the night when all
the useful typists have gone home at five o'clock. He is
personally involved in his work, as the poet is in his, and as
the artist is in the painting.
8. FROM THE SCIENCEWEEK ARCHIVE
COGNITIVE SCIENCE: NUMBERS AND COUNTING IN A CHIMPANZEE
A chimpanzee that has learned to use Arabic numerals to represent
numbers of items, and that can count from 0 to 9 items, is now
shown to remember the correct sequence of any 5 numbers selected
from the range 0 to 9.
9. SOURCES
=-=-=-=-=-=-=-=-=
Section 2
=-=-=-=-=-=-=-=-=
1. IN BRIEF:
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SNOWBALL EARTH
The late Proterozoic time-frame marked the first appearance of
multicellular animals, perhaps as early as 1000 to 700 million
years ago, and extensive glaciation may have exerted a
significant stress on living forms during a critical interval
in their evolution. Recent work has focused attention on the
Neoproterozoic time-frame by interpreting new carbon isotope data
to indicate that biological productivity of the oceans virtually
ceased for perhaps millions of years during the glacial era, and
from this work and from other evidence it has been concluded that
the planet entered a "snowball Earth" state, in which it was
completely covered by ice until carbon dioxide outgassing
produced a sufficiently large greenhouse effect to melt the ice.
In this scenario, the sudden warming caused a rapid precipitation
of calcium carbonate, producing certain types of carbonate rocks
often observed in strata of this era. Richard A. Kerr (2001)
reports on discussions of the snowball Earth hypothesis at a
recent meeting of the American Geophysical Union. An alternative
model to snowball Earth that is apparently gaining support, the
model involving cold and permafrost in the tropics, but
temperatures not low enough to freeze over the ocean and threaten
life with extinction. The new model stresses the importance of
the release of methane into shallow seas. Proof will require
finding the isotope signature of methane in carbonate cements.
(SCI 2001 292:2241) (NAT 2000 405:425)
-------------------------------------
CARBON DIOXIDE REMOVAL BY FORESTS
Steven C. Wofsy (2001) discusses the removal of atmospheric
carbon dioxide by forests. Emission rates of carbon dioxide from
combustion of fossil fuel have increased almost 40 percent in the
past 20 years, but the amount of carbon dioxide accumulating in
the atmosphere has remained the same or even declined slightly.
The reason for this discrepancy is that increasing amounts of
anthropogenic carbon dioxide are being removed by forests and
other components of the biosphere. It is estimated that more than
2 billion metric tons of carbon -- equivalent to 25 percent of
the carbon emitted by fossil fuel combustion -- are sequestered
by forests each year. Inverse models for studying atmospheric
concentrations of carbon dioxide suggest that mid-latitude
forests in North America and northern Eurasia are crucial carbon
sinks that remove this carbon dioxide from the atmosphere. But
analyses of forest inventories (which measure forest areas and
timber volume) seem to indicate that forests sequester much
smaller amounts of carbon. Thus we have a mystery. If our forests
have been sequestering billions of tons of carbon annually, why
can't we find it? It appears that most of the carbon dioxide that
is sequestered is in the organic matter of forests that is not
considered valuable and so is not reported in forest inventories:
woody debris, soil, wood products preserved in landfills, and
woody plants that have encroached on grasslands because of the
long-term suppression of natural fires. (SCI 2001 292:2261,2316)
-------------------------------------
CHEMICAL SYSTEMS AND PHASE SPACE TRAJECTORIES
Jullien and Lemarchand (2001) consider the use of the phase space
concept in chemistry. The evolution of various kinds of systems
known to physics, biology, chemistry, and economics can be
approached via the same mathematical model, a nonlinear system of
ordinary differential equations. Although such systems of
equations often have no analytical solutions, geometric theory
provides a powerful tool to describe the qualitative behavior of
a system. The primary concept in this geometric theory of dynamic
systems is the concept of "phase space", which is merely the
space of the dynamic variables that are considered by the
observer to be affected by the evolution of the system. A simple
example of such a phase space involves a mechanical system such
as an oscillating spring (mass (m), stiffness constant (k)). When
the spring is constrained to move along an axis (X), the abscissa
(x) and the corresponding impulsion (p) are sufficient for
describing the system states at any time. The phase space is then
the 2-dimension space (x,p), and differential equations for (x)
and (p) are derived from the laws of mechanics. In chemistry, at
a chosen macroscopic level of description, one often finds
similar components: 1) A set of state variables, such as the
quantities of the species present, is supposed to be sufficient
to describe the state at any time. These variables define the
phase space. 2) Some constraints, e.g., a closed system, fix the
value of certain combinations of the state variables as the total
number of each kind of atom. 3) The dynamic laws can be modeled
by a set of differential equations for the state variables.
(JCE 2001 78:803)
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CRYSTAL STRUCTURES OF A BIOMOLECULAR MOTOR
"Motor proteins" are mechanico-chemical enzymes involved in
locomotion of cells or transport of materials in cells, and there
are three families of such proteins: kinesins, dyneins, and
myosins. Kinesins and dyneins are microtubule-based motor
proteins, while myosin is a microfilament-based motor protein.
Kinesin is apparently present in all eukaryotic cells. The form
of kinesin originally discovered is a soluble rod-shaped molecule
composed of two polypeptide chains, the molecule travelling
toward one specific end of microtubules (depending on the type of
kinesin, either the so-called "plus" end or "minus" end. Kinesin
motors apparently power many cellular motile processes by
converting ATP energy into unidirectional motion along
microtubules. Although numerous biochemical and biophysical
studies have accumulated much data that link microtubule-assisted
ATP hydrolysis to kinesin motion, the structural view of kinesin
movement has remained unclarified. A new study of a monomeric
kinesin motor combines x-ray crystallography and cryo-electron
microscopy to allow analysis of force-generating conformational
changes at atomic resolution. The kinesin motor is revealed in
its two functionally critical states -- complexed with adenosine
diphosphate and with a non-hydrolyzable analog of adenosine
triphsophate. The conformational change is apparently modular,
extending to all kinesins, and is similar to the conformational
change used by myosin motors and G proteins. (NAT 2001 411:439)
-------------------------------------
NOTCH SIGNALING AND VASCULOGENESIS
The construction of an organism from a single egg cell to a
multicellular 3-dimensional structure of characteristic shape and
size is the result of coordinated gene action that directs the
developmental fate of individual cells. So-called "Notch-
signaling", a mechanism conserved in evolution, is used by
multicellular animals to control cell fates through local cell
interactions, and the realization by researchers that this
signaling mechanism controls an unusually broad spectrum of cell
fates and developmental processes (in organisms ranging from sea
urchins to humans) has in the past decade resulted in a large
number of Notch-related studies. Thomas Gridley (2001) discusses
current research on Notch signaling during vascular development.
Formation of the cardiovascular system is one of the earliest and
most important events during embryogenesis in mammals. During the
early stages of vascular development in both the mammalian embryo
and its extra-embryonic membranes (e.g., the yolk sac),
endothelial cell precursors differentiate and proliferate in a
process called "vasculogenesis". These endothelial cells then
coalesce and form the primary vascular plexus, a network of
homogeneously-sized primitive blood vessels. This vascular
network is then remodeled by the process of angiogenesis, which
involves the sprouting, branching, splitting, and differential
growth of vessels in the primary plexus to form the large and
small vessels of the mature vascular system. A number of
different signaling pathways have been implicated in the control
of these processes, and new evidence now adds the Notch signaling
pathway to this list. (PNAS 2001 98:5377,5643)
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BACTERIAL PATHOGENS AND PROTEIN SECRETION
In general, the term "pathogenicity" describes the ability of a
microbe to cause clinically apparent symptoms. In contrast, the
term "virulence" is used to describe microbes that cause severe
disease. Lee and Schneewind (2001) review the importance of
protein secretion in bacterial pathogenesis. Many bacterial
pathogens have evolved to enter and multiply within blood-
circulated tissues, and the underlying pathogenic strategies are
remarkably diverse and often result in unique disease symptoms.
Nevertheless, all mechanisms of bacterial manipulation of host
organisms can be viewed with respect to three different
categories: microbial adhesion to cell surfaces, secretion of
toxins into the extracellular milieu, and injection of virulence
factors into host cells. All bacterial secretion systems are
apparently highly evolved and efficient, with specificity in the
selection and transport of secretion substrates, the assembly of
the secretion machinery, and the coordinated movement of
macromolecules across one, two, or three lipid bilayers. In
general, protein secretion is a major aspect of successful
bacterial pathogenesis. Bacterial protein secretion is a rapidly
evolving field of research, but most of the work has been
performed with gram-negative organisms. A shift in focus is
needed, since gram=positive microbes cause many important human
diseases that are still poorly understood. (GD 2001 15:1725)
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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 nongenetic
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. (JAMA 2001 285:2831)
-------------------------------------
ANCIENT AGRICULTURE IN MEXICO
Dolores R. Piperno discusses the origins of agriculture and
recent evidence for the cultivation of maize more than 7000 years
ago in Mexico. Food surpluses made possible by agricultural
economies have fueled major cultural developments during the past
10,000 years, culminating in the emergence of urban societies and
advanced civilizations around the world. The current consensus is
that agriculture arose independently in 6 to 8 regions of the
world, including both hemispheres of the Americas, after
termination of the last Ice Age 12,000 years ago. Mexico was one
of the primary centers of agriculture with domestication of
maize, and new evidence suggesting that it was also a birthplace
of another important American crop plant, the sunflower
(Helianthus annuus L.). The earliest macrofossils (cobs) of maize
have been found in the arid highland Tchuacan and Oaxaca valleys.
It has been argued on the basis of these macrofossils that corn
was domesticated much later, approximately 6000 years ago, than
other major cereals such as wheat and rice. But recently K. Pope
et al (2001) reported the recovery of 7100-year-old maize pollen
from the San Andres site on the tropical coast of Mexico, the
sample in association with indicators of land-clearance resulting
from slash-and-burn cultivation. This is the oldest evidence for
maize in Mexico, predating the earlier macrofossil evidence by
1000 years. (SCI 2001 292:1370,2260)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
2. THEORETICAL PHYSICS: THE WEAKNESS OF GRAVITY
According to Newton's law of gravitation, there is a force
of attraction between any two massive particles in the Universe.
This force of attraction, as stated by Newton, may be expressed
as a simple relationship involving the masses of the two
particles and the distance between them. When the two masses are
unit masses and the distance between their centers of mass is
unit distance, then the force of attraction is equal to what is
called the "gravitational constant", usually denoted as "G". The
gravitational constant is usually regarded as a true universal
constant independent of place or time, but in some cosmological
models it is proposed that the gravitational constant decreases
with time as the Universe expands.
... ... Frank Wilczek (Massachusetts Institute of Technology, US)
discusses the relative extreme weakness of gravitational
interactions. Gravity dominates the large-scale structure of the
Universe, but only by default: matter arranges itself to cancel
electromagnetism, and the *strong and weak forces are
intrinsically short range. At a more fundamental level, gravity
is extremely weak: acting between protons, gravitational
attraction is approximately 10^(-36) times weaker than electrical
repulsion. The author asks: "Where does this outlandish disparity
come from? What does it mean?"
The author points out that these questions greatly disturbed
Richard Feynman (1918-1988). In 1963, in Feynman's famous paper
on quantizing general relativity, the paper in which he first
described his discovery of the "ghost particles" that eventually
played a crucial role in understanding modern *gauge field
theories, Feynman noted that the correct problem is to understand
what determines the size of gravitation.
Wilczek points out that the same question drove Paul Dirac
(1902-1984) to consider, 30 years before Feynman, the radical
idea that the fundamental "constants" of nature are time
dependent, so that the weakness of gravity could be related to
the great age of the Universe. Dirac's argument was that the
expansion rate of the Universe suggests that it began with a bang
approximately 10^(17) seconds ago. On the other hand, the time it
takes light to cross the diameter of a proton is approximately
10^(-24) seconds, which provides a ratio, 10^(-41), which is not
so far from the mysterious 10^(-36). But the age of the Universe,
of course, changes with time, so if the numerological coincidence
is to abide, something else -- the relative strength of gravity
or the size of protons -- will have to change in proportion.
Since there are powerful experimental constraints on such
effects, Dirac's idea is not easy to reconcile with standard
modern theories of cosmology and fundamental interactions,
theories which are extremely successful.
Wilczek discusses the dimensionless number N = Gm^(2)/hc,
where (G) is Newton's constant, (m) is the mass of the proton,
(h) is Planck's constant, and (c) is the speed of light.
Substituting measured values, we find N is approximately 3 x
10^(-39), and Wilczek notes: "This is what we mean when we say
gravity is extravagantly feeble." But the real problem, Wilczek
suggests, is to understand the smallness of N.
Wilczek then proposes that an understanding of the smallness
of N can be derived from an understanding of the smallness of the
mass of the proton, and in particular from the constraints
imposed by the *theory of quantum chromodynamics on the coupling
constants between quarks, the fundamental components of the
proton. Essentially, the inter-quark coupling force increases
with distance between quarks, which provides a powerful
constraint on the size and mass of the proton. The smallness of
N, therefore, is an apparent natural consequence of the theory of
quantum chromodynamics.
-----------
Frank Wilczek: Scaling Mount Planck I: A view from the bottom.
(PT 2001 June)
QY: Frank Wilczek: wilczek@mit.edu
-----------
Text Notes:
... ... *strong and weak forces: The weak forces are the
forces responsible for the change of neutrons and protons into
each other in radioactive processes and in the stars. The strong
forces are the forces that hold quarks together inside protons
and neutrons, and that hold protons and neutrons together inside
atomic nuclei.
... ... *gauge field theories: Quantum field theory is the
mathematical fusion of quantum mechanics with special relativity
theory, and there are essentially 2 branches: quantum
electrodynamics (applicable to charged particles involved in
electromagnetic interactions) and quantum chromodynamics
(applicable to nuclear particles involved in strong force
interactions). In this context, a "gauge theory" is any quantum
field theory which has the property of "gauge symmetry", i.e.,
the equations describing the field do not change when some
operation is applied to all particles everywhere in space. In
general, fields with gauge symmetry can be remeasured (regauged)
from different baselines without affecting their properties.
Quantum electrodynamics and quantum chromodynamics are examples
of gauge theories.
... ... *theory of quantum chromodynamics: Quantum chromodynamics
(QCD) is a theory that describes the strong interaction (strong
nuclear force) in terms of quarks and antiquarks and the exchange
of massless "gluons" between them. The "chromo-" in
chromodynamics derives from the use of designated "color"
attributes of quarks, the various "colors" labels for various
quark properties.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Aug01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON QUANTUM GRAVITY
"Gravity is by far the weakest force in the Universe: in the
hydrogen atom, the electromagnetic force between the proton and
electron is about 10^(40) times as great as the gravitational
force between them. This is fairly representative of the
difference in scales between the quantum and gravitational
realms, and accounts for our ability [in cosmology] to separate
the two theories without ambiguity. Yet they must inevitably
meet. Near a singularity, the curvature of space-time must be so
great that the scale of gravity becomes comparable to that of the
other fundamental forces. To describe such a state, we must find
a theory of quantum gravity. Moreover, quantum mechanics has
already been applied to the explanation of the other three
forces, the electromagnetic force and the strong and weak
interactions; should not gravity be similar? It might seem as
though the challenge of developing quantum gravity should not be
so great. After all, special relativity and quantum mechanics
were united in the 1920s by the British physicist Paul A.M.
Dirac. The most significant result of Dirac's theory was its
requirement that antiparticles exist, a prediction that was
confirmed in 1932 by the discovery of the positron (the anti-
electron). The Dirac theory is now well-established as the
special relativistic quantum mechanics. More than 70 years later,
however, general relativity has still not been successfully
incorporated into a consistent quantum formulation."
-----------
J.F. Hawley and K.A. Holcomb: Foundations of Modern Cosmology
(Oxford University Press, New York 1998, p.441)
(SW 1999 30 July)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
3. THEORETICAL PHYSICS: ENTROPY AND TIME
From an operational standpoint, "time" is a dimension that
enables two otherwise identical events that occur at the same
point in space to be distinguished, and the interval between two
such events forms the basis of time measurement. With that said,
it must also be said that time is one of the great puzzles of
physics and philosophy. Time is the most fundamental aspect of
our experience, with properties that have intrigued and baffled
philosophers, theologians, and scientists for centuries. Long-
standing controversies have focused on the following questions:
Was there a beginning of time? Will there be an end of time? What
distinguishes past from future? What is the "present" moment and
why does it "move"? Does time even exist as a separate physical
entity, or is it merely a construct of our world description?
... ... Victor J. Stenger (University of Hawaii, US) presents an
essay on the physical nature of time, the author making the
following points:
1) The author points out that Ludwig Boltzmann (1844-1906)
noted that the Second Law of thermodynamics is not a
deterministic law of physics but rather a statement of
probabilities. In 1928, Arthur Eddington (1882-1944) introduced
the expression "arrow of time" to represent the apparent one-way
property of time that has no analogue in space. Eddington
associated the arrow with an increasing random element in the
state of the world, as expressed by the Second Law of
thermodynamics. Eddington recognized that molecular motions were
intrinsically reversible, but that they tend to lose their
organization and become increasingly shuffled with time.
Eddington regarded the Second Law of thermodynamics as a
fundamental principle of the Universe, stating that it occupied
"the supreme position among the laws of nature." Eddington,
however, did not address the basic issue of why the molecules
were organized in the first place.
2) The author (Stenger) points out that the *entropy of the
Universe today is approximately 100 orders of magnitude greater
than it was in the very early Universe, and it is at least 23
orders of magnitude lower than it will be eventually as the
Universe approaches *heat death. This huge entropy difference
defines a cosmological arrow of time. Roger Penrose has argued
that the existence of the cosmological arrow requires a new law
of physics and that *quantum gravity is about the only place left
to look for such a law. However, the cosmological and
thermodynamic arrows of time are clearly related, for in each
case we have fully or partially isolated systems where the
entropy increases along the same time direction, and we choose
the positive time axis to point in the common direction. H. Price
(1996) has pointed out that the issue is not that an entropy
gradient leads to an arrow of time, but the issue is explaining
the source of that gradient.
3) The author (Stenger) asks: Why is the entropy so low at
one end of the time axis and so high at the other end? It has
been suggested that the exponential *inflation now believed to
have occurred in the first tiny fraction of a second of the Big
Bang provides the answer. But some have questioned this idea,
pointing out that this approach involves assuming a time
direction to begin with and then having the time direction appear
as a result. However, the author (Stenger) proposes that the
cosmological inflationary basis of directional time can be made
to work. The author (Stenger) suggests that the idea is to
maintain underlying time symmetry while allowing "localized"
violations, a trick that has worked for considerations of
symmetries in particle physics. Like those symmetries, time
symmetry becomes a global rule that is locally broken, where by
"local" is meant the region of space-time occupied by our
Universe since the beginning of the Big Bang. Let the Big Bang
begin at an arbitrary point on the time axis labelled t = 0.
According to the inflationary Big Bang model, the Universe was
empty of matter and radiation at that time. However, it was not
nothing. A quantum fluctuation in the presumably preexisting
nothing produced a non-zero curvature that appears in Einstein's
general relativity equations as the infamous "*cosmological
constant". According to an analysis of inflation by the author
(Stenger), "we get a completely time-symmetric inflation on both
sides of the t-axis: two universes (really the same universe),
one with its time arrow forward in conventional time and one with
its time arrow going in the opposite direction. The universe as a
whole is then time-symmetric. Although a huge 'local' asymmetry
exists on our side of the t-axis, it is matched by a similar
local asymmetry on the other side."
-----------
Victor J. Stenger: Time's arrows point both ways.
(SK 2001 8:4:90)
QY: Victor J. Stenger: vstenger@mindspring.com
-----------
Text Notes:
... ... *entropy: In general, entropy is measure of the
unavailability of the energy of a system to do work. All real
processes are to a certain extent irreversible changes, and in
any closed system an irreversible change is always accompanied by
an increase in entropy. Entropy can also be interpreted as a
measure of disorder: the higher the entropy, the greater the
disorder. Since all real changes in a closed system involve an
increase in entropy, the entropy of the Universe (if it can be
considered a closed system) is increasing. In this context, the
term "closed system" refers to an isolated system, i.e., a system
that cannot exchange matter or energy with its surroundings and
can therefore attain a state of thermodynamic equilibrium.
... ... *heat death: In this context, the term "heat death"
refers to the condition of the Universe when entropy is maximized
and all large-scale samples of matter are at a uniform
temperature. In this condition, no energy is available for doing
work. The condition of heat death was predicted by Rudolf
Clausius (1822-1888), who introduced the concept of entropy. The
dictum of Clausius that the energy of the Universe is constant
and its entropy tends to a maximum is essentially a statement of
the first two laws of thermodynamics. These laws apply in this
sense only to a closed system, and for the predicted heat death
to occur, the Universe must be a closed system.
... ... *quantum gravity: Quantum field theory is the
mathematical fusion of quantum mechanics with special relativity
theory, and the term "quantum gravity" refers to the fusion of
quantum mechanics with general relativity theory. The essential
basis for these fusions is the so-called "equivalence principle",
which identifies the mass involved in the gravitational force
equation with the inertial mass in the equation that relates any
force to the product of inertial mass and acceleration.
... ... *inflation: The inflationary model, first
proposed by Alan Guth in 1980, proposes that quantum
fluctuations in the time period 10^(-35) to 10^(-32) seconds
after time zero were quickly amplified into large density
variations during the "inflationary" 10^(50) expansion of the
universe in that time frame.
... ... *cosmological constant: In cosmology, the "cosmological
constant" is a mathematical term introduced by Einstein into the
equations of general relativity, the purpose to obtain a solution
of the equations corresponding to a "static universe". The term
describes a pressure (if positive) or a tension (if negative)
which can cause the Universe to expand or contract even in the
absence of any matter. In other words, the cosmological constant
represents an effective "vacuum energy". When the expansion of
the Universe was discovered, Einstein apparently began to regard
the introduction of this term as a mistake, and he described the
cosmological constant as the "greatest mistake of my life". But
the term has reappeared as the proposed source of apparent
accelerated cosmic expansion.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Aug01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
HISTORY OF PHYSICS: ON THE MEASUREMENT OF TIME
Although a verbal definition of time (other than a purely
operational definition) presents philosophical difficulties, from
the standpoint of physics, time is the most accurately measured
physical quantity. In general, there are two independent and
fundamental time scales: a) the dynamical time scale, which is
based on the regularities of the motions of the celestial bodies
fixed in their orbits by gravitation; b) the atomic time scale,
which is based on the characteristic frequency of electromagnetic
radiation emitted or absorbed in quantum transitions between
internal energy states of atoms or molecules.
The first known device for indicating the time of day was
the "gnomon", which appeared in approximately 3500 BC. This
instrument consisted of a vertical stick or pillar, the length of
the shadow cast by the stick or pillar providing an indication of
the time of day. By the 8th century BC, more precise devices were
in use. The earliest known sundial still preserved is an Egyptian
shadow clock dating at least from the 8th century BC, and which
consists of a straight base with a raised crosspiece at one end.
On the base is inscribed a scale of 6 time divisions. The base is
placed in an east-west direction with the crosspiece at the east
end in the morning and at the west end in the afternoon. The
shadow of the crosspiece on the base indicates the time.
The Babylonian hemispherical sundial (hemicycle), apparently
invented by the astronomer Barosus in approximately 300 BC,
consisted of a cubical block into which was cut a hemispherical
opening. To the opening was fixed a pointer whose end lay at the
center of the hemispherical space. The path traveled by the
shadow of the pointer was approximately a circular arc whose
length and position varied according to the seasons. An
appropriate number of arcs were inscribed on the internal surface
of the hemisphere, each arc divided into 12 subdivisions. Each
day, reckoned from sunrise to sunset, had 12 equal intervals or
"hours". Since the length of the day varied according to the
season, these hours were known as "temporary hours".
The Greeks developed and constructed sundials of
considerable complexity in the 3rd and 2nd centuries BC,
including instruments with either vertical, horizontal, or
inclined dials, indicating time in temporary hours. The Romans
also used sundials with temporary hours, and some of these Roman
sundials were portable. The Arabs increased the variety of
sundial designs, and at the beginning of the 13th century AD the
Arabs wrote on the construction of sundials with cylindrical,
conical, and other surfaces.
In general, a "clock" is a device that performs regular
movements in equal intervals of time, the device linked to a
counting mechanism that records the number of movements. The
first public clock that struck the hours was made and erected in
Milan (IT) in 1335. The oldest surviving clock is that at
Salisbury Cathedral, which dates from 1386. In approximately
1500, small portable clocks driven by a spring appeared, the
dials with an hour hand only. The pendulum was applied as a time
controller in clocks beginning in 1656, although Galileo had
already suggested this in 1582. The familiar subdivision of the
day into 24 hours, the hour into 60 minutes, and the minute into
60 seconds is of ancient origin, but these subdivisions came into
general use in approximately 1600 AD. When the increasing
accuracy of clocks led to the adoption of the "mean solar day",
which contained 86,400 seconds, the "mean solar second" became
the basic unit of time. The adoption of the International System
(SI) second, defined on the basis of atomic phenomena, as the
fundamental time unit, occurred provisionally in 1964 and finally
in 1967. A second is now defined as 9,192,631,770 cycles of
radiation associated with the transition between the two
hyperfine levels of the ground state of the cesium-133 atom. The
number of cycles of radiation was chosen to make the length of
the defined second correspond as closely as possible to that of
the previous standard, the astronomically determined second of
"Ephemeris Time" (defined as 1/(86,400) of the mean solar day).
... ... J.C.Bergquist et al (3 authors at National Institute of
Standards and Technology, US) present a review of current
research on precision atomic clocks, the authors making the
following points:
1) The authors point out that although a unit of time can be
constructed from other physical constants, time is usually viewed
as an arbitrary parameter to describe dynamics. The frequency of
any periodic event, such as the mechanical oscillation of a
pendulum, or the quantum oscillation of an atomic dipole, can be
adopted to define the unit of time, the second.
2) For centuries, the mean solar day served as the unit of
time, but Earth's period of rotation is irregular and slowly
increasing. In 1956, the International Astronomical Union and the
International Committee on Weights and Measures recommended
adopting Ephemeris Time, based on Earth's orbital motion around
the Sun, as a more accurate and stable basis for the definition
of time. This recommendation was formally ratified in 1960 by the
General Conference on Weights and Measures.
3) Until the definition of the second in terms of atomic
time in 1967, most work in standards laboratories was devoted to
developing secondary standards, such as lumped-element circuits
and quartz crystals, whose resonant frequencies could be
calibrated relative to Ephemeris Time. But frequencies derived
from resonant transitions in atoms or molecules offer important
advantages over macroscopic oscillators. Any unperturbed atomic
transition is identical from atom to atom, so two clocks based on
such a transition should generate the same time. Also, unlike
macroscopic devices, atoms do not wear out, and as far we know
they do not change their properties over time.
4) The basic idea of most atomic clocks is straightforward:
a) First, identify a transition between two non-degenerate energy
states of an atom. b) Then, create an ensemble of these atoms
(e.g., in an atomic beam or storage device). c) Next, illuminate
the atom with radiation from a tunable source that operates near
the transition frequency. d) Sense and control the frequency
where the atoms absorb maximally. e) When maximal absorption is
achieved, count the cycles of the oscillator: a certain number of
elapsed cycles generates a standard interval of time. But
although the general idea of an atomic clock is straightforward,
in practice there are a number of experimental difficulties that
limit accuracy. The latest atomic clocks use a single ion to
measure time with an anticipated precision of one part in
10^(18).
-----------
J.C. Bergquist et al: Time measurement at the Millennium.
(PT March 2001)
QY: James C. Bergquist: National Institute of Standards and
Technology, Boulder CO, US.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 23Mar01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON PLANCK, BOLTZMANN, AND ENTROPY
"If there is a single concept that unifies the long and fruitful
scientific career of Max Planck, it is the concept of entropy.
From the Munich dissertation which he wrote at the age of 21,
right through to the papers he wrote during his late seventies,
the Second Law of Thermodynamics and the associated idea of
entropy were always central in his thought. Although much of his
work can be viewed as an extended series of variations on what he
called his pet theme ("Lieblingsthema"), the theme itself was
radically altered in 1900. In that year Planck introduced, in his
theory of the black-body radiation spectrum, the idea which
immortalized his name, the idea of energy quanta. This idea grew
directly from Planck's years of study of the way in which the
second law of thermodynamics applied to the behavior of
radiation. But despite its connections with his work on entropy
during the previous 20 years, it was the very success of his
theory of radiation that forced Planck to make a thorough
revision of his ideas on entropy. Before 1900, Planck had
resolutely followed the single line of pure thermodynamics in his
work, avoiding the difficulties that surrounded the path of
kinetic theory. He was willing to grant that the attempts to
expose the molecular basis of macroscopic behavior offered the
hope of more fundamental insight into nature; but he expressed
his doubts, on more than one occasion, that these attempts to dig
deeper than the laws of thermodynamics could meet with real
success in the foreseeable future. At no point in any of the 40
or so papers that he wrote prior to 1900 did Planck use, or even
refer to, the relationship that Ludwig Boltzmann had discovered
between entropy and the probability of molecular configurations.
The muse of entropy was as dear to Boltzmann's heart as to
Planck's, but how different she appeared to her two admirers!"
-----------
Martin J. Klein: Planck, Entropy, and Quanta, 1901-1906.
(The Natural Philosopher 1963 1:83)
-------------------
SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
4. MEDICAL BIOLOGY: BRAIN DEATH
There is currently a widespread legal and societal
acceptance that death of a person is the total cessation of
integrated brain function, especially cessation of function of
the *brainstem. To a considerable degree, this acceptance was in
recent years forced by the capacity of ventilators to perpetuate
cardiopulmonary function for a considerable time despite failure
of other organs. The diagnosis of brain death is not trivial, and
various countries have instituted protocols for such a diagnosis,
protocols which are critical when a "brain dead" body is to be
used for medical purposes, including the donation of
transplantable organs. Brain death is a neurological condition,
and the diagnosis is therefore ultimately based on current
understanding of neurophysiological processes.
... ... Eelco F.M. Wijdicks (Mayo Clinic, US) reviews current
protocols and procedures in the diagnosis of brain death, the
author making the following points:
1) The author points out that there is a clear difference
between severe brain damage and "brain death", and that it is
important to understand this difference, since brain death means
that life support is useless, and brain death is the principle
requisite for the donation of organs for transplantation. In
adults, the chief causes of brain death are traumatic brain
injury and *subarachnoid hemorrhage. In children, abuse is a more
common cause than motor vehicle accidents or asphyxia.
2) Because of the widespread use of mechanical ventilators
that prevent respiratory arrest, vital functions can now be
maintained artificially after the brain has ceased to function.
From a clinical standpoint, among the criteria of brain death in
adults and children are the following:
Absence of breathing (apnea)
Coma
Absence of motor responses
Absence of pupillary responses to light
Absence of corneal reflexes
Absence of *oculovestibular caloric responses
Absence of gag reflex
Absence of coughing in response to tracheal suctioning
Absence of *sucking and rooting reflexes (in infants)
3) The author points out that the most controversial issue
related to the determination of brain death is the occurrence of
clinical signs that suggest some retention of brain function.
Even in the absence of motor responses, spontaneous body
movements may be observed during the apnea test, while the body
is being prepared for transport, at the time of an abdominal
incision for the retrieval of organs, or in synchrony with the
respiration produced by the mechanical ventilator. These body
movements are generated by the spinal cord, and the evidence of
brain death in such cases comes from a consistent clinical
documentation of brain death and confirmation by
*electroencephalography or *cerebral angiography. These slow body
movements may even include a brief attempt of the body to flex at
the waist, making it seem to rise. The arms may be raised
independently or together. Forceful flexion of the neck or
rotation of the body may initiate these movements. Legs seldom
move spontaneously. Other manifestations that have been reported
are a slow turning of the head to one side, facial twitching, a
persistent *Babinski reflex, and tendon and other reflexes.
4) The author points out that misdiagnosis of brain death is
possible if an infarct occluding the *basilar artery (locked-in
syndrome), hypothermia, or drug intoxication is not recognized.
a) The locked-in syndrome is usually a consequence of the
destruction of part of the brainstem (destruction of the base of
the pons). The patient cannot move the limbs, cannot grimace or
swallow, but brainstem structures involved in voluntary blinking
and vertical eye movements remain intact. Consciousness persists
because the *reticular formation of the brainstem is not
affected. The condition is most often caused by an acute *embolus
in the basilar artery. More dramatic is the reversible *Guillain-
Barre syndrome involving all the peripheral and cranial nerves:
the progression occurs over a period of days, and knowledge of
the patient's history should prevent the dangerous error of a
diagnosis of brain death.
b) Accidental hypothermia from prolonged environmental
exposure may mimic loss of brain function, but alcohol
intoxication and head injury often confound diagnosis in these
cases. Hypothermia causes a downward spiral of loss of brainstem
reflexes and pupillary dilatation. The response to light is lost
at core temperatures of 28 to 32 degrees Celsius, and brainstem
reflexes disappear when the core temperature drops below 28
degrees Celsius. These deficits are all potentially reversible,
even after extreme hypothermia.
c) The effects of many sedative and anesthetic agents
can closely mimic brain death, but aspects of brainstem function,
particularly the pupillary responses to light, remain intact.
When ingested in large quantities, many drugs can cause a partial
loss of brainstem reflexes.
5) The author points out that confirmatory testing of brain
death by a battery of physical methods (cerebral angiography,
electroencephalography, *transcranial ultrasonography, *cerebral
scintigraphy) is required in several European, Central and South
American, and Asian countries. Certain countries (e.g., Sweden)
require only cerebral angiography. In the US, the choice of tests
is left to the discretion of the physician, but bedside tests
seem to be preferred.
-----------
Eelco F.M. Wijdicks: The diagnosis of brain death.
(NEJM 2001 344:1215)
QY: Eelco F.M. Wijdicks: wijde@mayo.edu
-----------
Text Notes:
... ... *brainstem: The brainstem is a phylogenetically old
region of the central nervous system that among other things
contains control centers for fundamental physiological processes
such as breathing and heart rate. Anatomically, the brainstem is
the connecting region between the brain above it and spinal cord
below it.
... ... *subarachnoid hemorrhage: The arachnoid is a delicate
membrane that forms one of the coverings of the central nervous
system (brain and spinal cord).
... ... *oculovestibular caloric responses: Irrigating the ear
canal with warm or cold liquid normally produces reflexive
movements of the eyes (nystagmus).
... ... *sucking and rooting reflexes: in infants, rubbing or
scratching around the mouth causes a puckering of the lips.
... ... *electroencephalography: Registration of time-varying
macroscopic electrical potential differences between various
parts of cranium. At brain death, the potential difference-time
function is essentially flat.
... ... *cerebral angiography: Radiographic visualization of
blood vessels supplying the brain.
... ... *Babinski reflex: This reflex, present in infants,
results from gentle stroking of the outer margin of the sole of
the foot. The great toe extends, with or without fanning of the
other toes. The normal reflex after 1.5 years of age is the
plantar flexion reflex ("negative Babinski"), which involves a
curling under of all the toes, accompanied by a slight turning in
and flexion of the anterior part of the foot.
... ... *basilar artery: A major artery of the upper brainstem.
... ... *reticular formation of the brainstem: A neural network
in the brainstem involved in the central control of respiration,
blood pressure, thermoregulation and other autonomic functions,
endocrine functions, bodily posture, skeletomuscular reflex
activity, and general behavior states such as alertness and
sleep.
... ... *embolus: In general, any mechanical obstruction.
... ... *Guillain-Barre syndrome: An acute immune system-mediated
disorder of peripheral and cranial nerves.
... ... *transcranial ultrasonography: Transcranial ultrasound
imaging.
... ... *cerebral scintigraphy: A diagnostic procedure consisting
of the administration of a radionuclide (e.g., technetium) with
an affinity for the organ or tissue of interest, followed by
recording the distribution of the radioactivity with a
scintillation camera.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Aug01
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
5. PUBLIC HEALTH: CANCER EPIDEMIOLOGY
Julian Peto (Institute of Cancer Research, UK) present an
extensive review of current research in cancer epidemiology, the
author making the following points:
1) The author points out that many types of cancers vary in
incidence by more than an order of magnitude between different
populations, and every type of cancer is rare in some part of the
world. The convergence towards local cancer rates seen among
immigrants excludes a genetic explanation of these differences.
By the 1960s, cancer epidemiologists had therefore concluded that
most cancers are in principle preventable and that many cancers
could be avoided by a suitable choice of lifestyle and
environment. Many specific causes of cancer are now known, the
most important being smoking, obesity, and a few oncogenic
viruses, but a large proportion of global variation for common
cancers such as breast, prostate, colon, and rectum remains
unexplained.
2) The most important discovery in the history of cancer
epidemiology is the carcinogenic effect of tobacco. Lung cancer
incidence increases rapidly among continuing smokers, so the risk
is greatest in those who begin to smoke when young and continue
throughout life. For many years, the carcinogenic effects of
tobacco were believed to be restricted largely to the lung,
pancreas, bladder, kidney, larynx, mouth, pharynx, and esophagus.
More recent evidence indicates that the risk for several other
types of cancer, of which the most important worldwide are
stomach, liver, and probably cervical cancer, are also increased
by smoking.
3) No single dietary factor shows a strong and consistent
enough effect to establish it unequivocally as an important
carcinogen or anti-carcinogen. Extensive research during the past
two decades has shown that rates for various cancers correlate
fairly consistently with certain aspects of diet, but opinions
still differ on the strength of the evidence. There is now a
consensus that cancer is commoner in those who are overweight,
with evidence strongest for post-menopausal breast cancer and
cancers of the endometrium, gall bladder, and kidney, but several
other sites contribute to the overall risk.
4) Breast cancer incidence is transiently increased by
pregnancy and while estrogens are administered as oral
contraceptives or hormone replacement therapy, and breast cancer
incidence is permanently lowered by late menarche, early
menopause, early first childbirth, and high number of pregnancies
(high parity). The development of cancers of the testis and
prostate may also depend on hormonal effects, but apart from the
increased risk associated with an undescended testis, no
behavioral or reproductive correlate is strongly predictive of
these diseases.
5) The most important discoveries of the past two decades in
cancer epidemiology relate to the carcinogenic effects of
infectious pathogens that had not been characterized 20 years
ago. Helicobacter pylori, a chronic gastric bacterial infection
that can cause gastric ulcers, is a major factor in the stomach
cancer. Some variety of human papillovirus is detectable in
virtually all cervical cancers worldwide. Such viruses are also
found in other anogenital cancers and may also cause cancers of
other sites (head and neck esophagus, skin). The contribution of
hepatitis-B virus to liver cancer has long been recognized,
although the synergistic effect of smoking is a more recent
discovery. The hepatitis-C virus is similarly carcinogenic.
Approximately one-fifth of all human cancers worldwide arise in
the stomach, liver, or cervix, and most of these cancers would be
prevented if these infections could be eradicated.
6) Other pathogens that cause a substantial cancer risk in
certain populations include Epstein-Barr virus (various B-cell
malignancies and nasopharyngeal cancer), malaria (Burkitt's
lymphoma), human T-cell lymphotropic virus type I (some T-cell
leukemias and lymphomas), HIV (non-Hodgkin's lymphoma), human
herpesvirus 8 (Kaposi's sarcoma, with HIV), schistosomiasis
(bladder and colon cancer), liver flukes (cholangiosarcoma).
There is also strong epidemiological evidence for an infective
etiology in childhood leukemia, but no specific pathogen has been
implicated. The incidence of several virally induced cancers is
further increased by specific cofactors such as dietary aflatoxin
(liver cancer), salted fish (nasopharyngeal cancer), and smoking
(liver and cervical cancer).
7) Tobacco causes one-third of all cancer deaths in
developed countries. Approximately 15 percent of cancers
worldwide re caused by known infectious agents. Hepatitis-B virus
alone causes almost as many cancers as smoking in China, and can
be prevented by vaccination. Human papilloma virus vaccines that
are already being tested may be able to prevent almost all
cervical cancers, and if the prevalence of Helicobacter pylori
can be reduced, many stomach cancers would be avoided. The
belated elimination of asbestos by many Western countries will
eventually prevent the great majority of mesotheliomas and many
lung cancers. Various cancer screening tests are partially
effective, and cervical cancer screening is very effective.
-----------
Julian Peto: Cancer epidemiology in the last century and the next
decade.
(NAT 2001 411:390)
QY: Julian Peto: Institute of Cancer Research, Sutton, Surrey SM2
5NG, UK.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 3Aug01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MEDICAL BIOLOGY: ORIGINS OF CANCER
In general, cancer involves a loss of normal cellular growth
control, the loss of control producing a growing tissue mass
called a "tumor" or "neoplasm". Uncontrolled growth occurs not
because the replication rate of cancer cells is always greater
than the replication rate of normal cells, but because of the
difference between the replication rate of cancer cells and the
rate of loss of cancer cells. In normal tissue, a precise balance
between replication rate and rate of loss is maintained; in a
growing neoplasm, this balance is absent and the replication rate
exceeds the rate of loss.
... ... Daniel Haber (Massachusetts General Hospital, US)
presents a review of the etiology of breast cancer, the author
making the following points concerning the origins of cancer in
general:
1) The author points out that cancer results from the
accumulation of mutations in genes that regulate cellular
proliferation. These mutations can occur early in the process of
malignant transformation or later, during progression to an
invasive carcinoma. The earliest mutations occur in the *germ
line, as in the case of cancer-prone families. In these
instances, the inheritance of a mutated *allele is commonly
followed by the loss of the second allele from a somatic cell,
leading to the inactivation of a tumor-suppressor gene and
triggering malignant transformation. A classic example is
hereditary retinoblastoma, in which there is inheritance of a
mutant germ-line _RBI_ allele (a *tumor-suppressor gene) followed
by somatic mutation of the normal _RBI_ allele.
2) Genes important to the development of cancer regulate
diverse cellular pathways, including the progression of cells
through the *cell cycle, resistance to programmed cell death
(apoptosis), and the response to signals that direct *cellular
differentiation. Moreover, the inactivation of genes that
contribute to the stability of the genome itself can favor the
acquisition of errors in other genes that regulate proliferation.
3) Errors in DNA that arise during normal replication of the
molecule (nucleotide mismatches), or that are induced by ionizing
radiation or genotoxic drugs, can cause mutations in coding
sequences or breaks in double-stranded chromosomal DNA. If the
nucleotide mismatch is not repaired before a round of DNA
replication occurs, that mutation is transmitted to daughter
cells. An unrepaired break in double-stranded DNA can cause a
mitotic catastrophe when the cell attempts to segregate broken
chromosomes. Studies of yeast have identified genes that sense
damaged DNA and cause the arrest of the cell cycle, which allows
time for the molecular defect to be repaired. These genes operate
at several specific "checkpoints" in the cell cycle as a means of
ensuring genomic integrity before DNA is synthesized.
4) The most critical checkpoint gene yet identified that is
related to cancer in humans is the tumor suppressor gene _p53_.
This gene is not essential for cell viability, but it is critical
for monitoring damage to DNA. Inactivation of _p53_ is an early
step in the development of many kinds of tumors. In cases of
cancer without _p53_ mutations, there are frequently alterations
in two other genes (_MDM2_ and _p14_) that regulate the
expression of _p53_.
-----------
Daniel Haber: Roads leading to breast cancer.
(NEJM 2000 343:1566)
QY: Daniel Haber: Massachusetts General Hospital, Boston, MA
02114 US.
-----------
Text Notes:
... ... *germ line: A germ cell is any cell from which gametes
(sperm cells and egg cells) are derived. All other cells are
called "somatic" cells. In general, the term "germ line" refers
to the line of differentiated germ cells.
... ... *allele: An allele is one of two or more forms of a
given gene that control a particular characteristic, with the
alternative forms occupying corresponding loci on homologous
chromosomes.
... ... *tumor-suppressor gene: In general, cancer genes have
been divided into 2 classes, proto-oncogenes and tumor suppressor
genes. Proto-oncogenes are genes that sustain activating changes
in human cancer. These changes may take the form of point
mutations or gene rearrangements that lead to increased or
uncontrolled activity of the encoded protein, or they make take
the form of gene amplification, which results in increased levels
of protein expression. In contrast, tumor suppressor genes are
characterized by inactivating changes in human cancer, typically
point mutations that result in truncation or functional
inactivation of the encoded protein, or gross deletions of
chromosomal fragments carrying these genes.
... ... *cell cycle: In this context, the term "cell cycle"
refers to the entire life history of a single cell from mitosis
to mitosis, including the sequence of intervening phases.
... ... *cellular differentiation: In general, in this context,
the term "differentiation" refers to the structural and
functional specialization of cells, developmental cell
specialization (morphology and biochemistry) resulting from
activation of specific parts of the cell genome.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MEDICAL BIOLOGY:
ENVIRONMENT VS. HEREDITY IN THE CAUSATION OF CANCER
There is considerable public confusion concerning the origin
of cancer. What we call "cancer" is essentially a set of diseases
of genes (see related background material below), but most
cancers are not inherited: the gene damage responsible for most
cancers is apparently produced by environmental factors affecting
the genetic information that controls replication of ordinary
tissue cells. In other words, the damaged gene (or genes)
responsible for a cancer is usually not inherited; most often the
damage is produced (or occurs spontaneously) during the life of
the individual.
Certain types of cancer are indeed apparently familial,
determined primarily by hereditary factors, but most types of
cancer are non-familial ("sporadic"), with an unclear
contribution of hereditary factors to the response of the
individual to environmental factors. In general, studies of twins
make it possible to estimate the overall contribution of
inherited genes to the development of cancer, and such studies
form the basis of current views of the heritability of various
cancers.
... ... P. Lichtenstein et al (9 authors at 7 installations, SE
DK FI) now report a study of data on 44,788 pairs of twins listed
in the Swedish, Danish, and Finnish twin-registries, the purpose
of the study to assess the risks of cancer at 28 anatomical sites
for the twins of persons with cancer. Statistical modeling was
used to estimate the relative importance of heritable and
environmental factors in causing cancer at 11 of those sites. The
authors conclude as follows: "We conclude that the overwhelming
contributor to the causation of cancer in the population of twins
that we studied was the environment. For some of the forms of
cancer, in which a shared environment is important, it may be
possible to find clues in studies of childhood environment or
long-lasting family habits. The relatively large heritability
proportions for cancers at some sites, despite the wide
confidence intervals, suggest major gaps in our understanding of
hereditable cancer. Even for cancers for which there is
statistically significant evidence of a heritable component, most
pairs of twins were discordant for the cancer -- indicating that,
on the population level, the increase in the risk of cancer even
among close relatives of affected persons is generally moderate."
-----------
P. Lichtenstein et al: Environmental and heritable factors in the
causation of cancer.
(NEJM 2000 343:78)
QY: Paul Lichtenstein [paul.lichtenstein@mep.ki.se]
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 28Jul00
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
6. NEUROSCIENCE: NATURE OF HUMAN EMOTIONS
Although what we call "emotions" certainly involve
significant events in the nervous system, and neural structures
strongly associated with emotions have been identified, most
advanced textbooks in neuroscience devote only minor space to
emotions, and some textbooks avoid the subject completely. There
are many reasons for this, and one reason is that despite the
scientific attention given to emotions by the archetypical
classical biologist Charles Darwin, human emotions (grouped as
"affect") are traditionally considered the investigative province
of psychology and psychiatry rather than a province of
neurobiology. But this attitude is rapidly changing. We certainly
know more now about the neurobiological correlates of emotions
than we did 50 years ago, and new techniques are making possible
important new research.
In general, all emotions are expressed through both
physiological changes and stereotyped motor responses, especially
responses of the facial muscles. These responses accompany
subjective experiences that although not easily described are
apparently much the same in all human cultures. Expression of the
emotions is closely tied to the autonomic nervous system, and it
therefore involves the activity of certain defined brain
structures (e.g., brainstem nuclei, hypothalamus, amygdala), as
well as autonomic nervous system components (e.g., preganglionic
neurons in the spinal cord, autonomic ganglia, peripheral
effectors). The brain centers that coordinate emotional responses
have been grouped as the "limbic system". At the level of the
cerebral cortex, the two hemispheres apparently differ in their
governance of the emotions, with the right hemisphere more
critically involved than the left hemisphere.
... ... Robert Plutchik (Albert Einstein College of Medicine, US)
presents a review of current ideas concerning the nature of human
emotions, the author making the following points:
1) The author points out that what we call "cognition" --
the activity of knowing, learning, and thinking, of which emotion
is a part -- evolved over millions of years. Charles Darwin
(1809-1882) recognized that the process of evolution by natural
selection applied not only to anatomic structures but also to the
"mind" of an animal and to expressive behavior, a conclusion that
led him to write a treatise on emotional expression (_The
Expression of Emotion in Man and Animals_, 1872). Those who have
followed Darwin in studying the evolutionary origins of emotions
have sought to understand how emotions increase evolutionary
fitness for the individual.
2) The author points out that an emotion is not simply a
feeling state: emotion is a complex chain of loosely connected
events, the chain beginning with a stimulus and including
feelings, psychological changes, impulses to action, and specific
goal-directed behavior. In other words, feelings do not happen in
isolation. They are responses to significant situations in the
life of an individual, and often they motivate actions. The
author suggests this definition of emotions allows the concept to
be generalized to lower animals without difficulty. From his
studies of animals, human infants, and human adults, Darwin
concluded that expressive behaviors communicate information from
one animal to another about what is likely to happen, and
emotions therefore affect the chances of survival of the
individual demonstrating the behavior. Darwin stated: "Even
insects express anger, terror, jealousy, and love by their
stridulations."
3) The author (Plutchik) proposes that in general emotions
are activated in an individual when issues of survival are raised
in fact or by implication. Such situations include threats,
attacks, poisonous substances, or the sighting of a potential
mate. The effect of the emotional state is to create an
interaction between the individual and the event or stimulus that
precipitated the emotion. The interaction usually takes the form
of an attempt to reduce the disequilibrium and reestablish a
state of comparative rest.
-----------
Robert Plutchik: The nature of emotions.
(AS 2001 89:344)
QY: Robert Plutchik: proban@home.com
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 3Aug01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
NEUROBIOLOGY: ON THE BRAIN AND VIOLENCE
Although human violence has been a major focus of research
in psychiatry, psychology, and the social sciences,
neurobiological studies of human violence have been relatively
uncommon. Neurobiology, however, is a major component in our
understanding of human behavior: genetics, environment, brain
structure and brain function are all involved in both ordinary
behavior and in violent behavior.
... ... C.M. Filley et al (3 authors at 3 installations, US)
present a commentary on current research on violence and the
human brain, the authors making the following points:
1) The authors point out that in adults, the role of brain
damage in violence remains unclear. A brain lesion by itself is
rarely sufficient to cause violent behavior, and most individuals
with brain damage do not commit criminal acts. But we cannot
assume that the brains of violent individuals are invariably
normal. The neurologic status of the brains of violent persons
has not been adequately assessed by detailed neurological
examination, neuropsychological testing, *magnetic resonance
imaging, or *functional neuroimaging. Studies of murderers have
suggested a high prevalence of neurologic dysfunction, and some
individuals with traumatic brain injury, epilepsy, dementia, and
sleep disorders have been observed to exhibit excessive violence.
Violence is more likely among those with severe mental illness,
particularly psychosis, and violence is exacerbated by the use of
alcohol and other psychoactive substances.
2) The authors point out that detailed analysis of the
neurobehavioral aspects of violence is complex:
... ... a) The cause of violence is multifactorial, and a direct
correlation between brain dysfunction and a violent act is rarely
possible.
... ... b) Identification of brain lesions is imperfect given the
limitations of diagnostic classifications, the limitations of the
neurologic examination, the limitations of neuroimaging
technologies, the limitations of neuropsychological assessment,
and the limitations of neurochemical analysis.
... ... c) Some subject samples, such as prisoners or those with
severe neurologic or psychiatric disease, are necessarily based
on violent persons who are apprehended or hospitalized.
Conclusions are therefore based only on those whose records are
analyzed, and the potential for violence in the general
population remains unknown.
3) There is the possibility of a neurogenetic contribution
to violent behavior. Although no single gene for human violence
has been discovered, data from molecular genetics indicate that
multiple genes may interact to predispose individuals to violent
behavior. Observations in mouse *knockout models have suggested
that targeted disruption of single genes can induce
aggressiveness in males and diminish nurturing in females.
Aggression in animals and humans is also likely related to genes
regulating central nervous system *serotonin metabolism.
4) In general, males are much more likely to commit violent
acts than are females, but genetic factors may not explain this
discrepancy. Socioeconomic and cultural influences play a major
role. Unemployment, lower educational level, alcohol abuse, and
access to firearms all contribute to violent crime among males.
The *XYY chromosomal disorder serves to highlight difficulties in
establishing an influence of gender on violence.
5) Although no "violence center" exists in the brain, the
*limbic system and the *frontal lobes are areas most implicated
in violence. The limbic system is the neuroanatomic substrate for
many aspects of emotion. The limbic system structure most often
implicated in violent behavior is the *amygdala: placidity has
been described in humans with bilateral amygdala damage, whereas
violence has been observed in those with abnormal electrical
activity in the amygdala. The frontal lobes are apparently the
areas of the most advanced functions of the brain. In particular,
the *orbitofrontal cortices are involved in the inhibition of
aggression: individuals with orbitofrontal injury have been found
to display antisocial traits that justify the diagnosis of
"acquired sociopathy", and some of these individuals have an
increased risk of violent behavior. A balance apparently exists
between the potential for impulsive aggression mediated by limbic
structures, and the control of this drive by the influence of the
orbitofrontal regions.
6) The authors conclude: "Whereas dysfunction of a discrete
brain region, isolated neurochemical system, or single gene will
not likely emerge as a direct cause of violence, all may
contribute."
-----------
C.M. Filley et al: Violence and the brain: An urgent need for
research.
(TS 2001 2 April)
QY: Christopher M. Filley: University of Colorado 303-492-6694.
-----------
Text Notes:
... ... *magnetic resonance imaging: Magnetic resonance imaging
(MRI) is essentially a technique for examining morphology (as
opposed to _functional_ magnetic resonance imaging, which is a
technique for examining anatomical correlates of function). In
general, MRI involves magnetic coils producing a static magnetic
field parallel to the long axis of the patient or subject,
combined with inner concentric magnetic coils producing a static
magnetic field perpendicular to the long axis. A radio-frequency
coil specifically designed for the head perturbs the static
fields to generate a magnetic resonance image. The interaction
physics in this technique is that between the magnetic fields and
atomic nuclei in brain tissue. "Sliced" views can be obtained
from any angle, and the resolution is quite high and on the order
of millimeters for magnetic field strengths of 1.5 tesla.
... ... *functional neuroimaging: Functional magnetic resonance
imaging (fMRI) is based on the fact that oxyhemoglobin, the
oxygen-carrying form of hemoglobin, has a different magnetic
resonance signal than deoxyhemoglobin, the oxygen-depleted form
of hemoglobin. Activated brain areas utilize more oxygen, which
transiently decreases the levels of oxyhemoglobin and increases
the levels of deoxyhemoglobin, and within seconds the brain
microvasculature responds to the local change by increasing the
flow of oxygen-rich blood into the active area. This local
response thus leads to an increase in the oxyhemoglobin-
deoxyhemoglobin ratio, which forms the basis for the fMRI signal
in this technique. Because of its high spatial resolution
(millimeters) and high temporal resolution (seconds) compared to
other imaging techniques, fMRI is now the technology of choice
for studies of the functional architecture of the human brain.
Positron emission (PET) tomography is a technique for producing
cross-sectional images of the body after ingestion and systemic
distribution of safely metabolized positron-emitting agents. The
images are essentially functional or metabolic, since the
ingested agents are metabolized in various tissues.
Fluoro-deoxyglucose and H(sub2)O(sup15) are common agents used
for cerebral applications, and in cerebral applications of
central importance to the technique is the fact that changes in
the cellular activity of the brains of normal, awake humans and
unanesthetized laboratory animals are invariably accompanied by
changes in local blood flow and also changes in oxygen
consumption.
... ... *knockout models: In general, in this context,
"knockout technology" involves the generation of a mutant
organism (usually a mouse) with a missing specific gene.
... ... *serotonin metabolism: A neurotransmitter substance
involved in nearly everything occurring in the brain, including
psychological states such as anxiety and depression, and
dysfunctions producing migraine and epilepsy.
... ... *XYY chromosomal disorder: Humans ordinarily have 46
chromosomes. Of this number, 44 are not sex-related and are
called "autosomal". Two chromosomes, X and Y, are sex-related. An
individual with two X chromosomes is a female; an individual with
one X and one Y chromosome is a male. Approximately 1 in 1000
males have an extra Y chromosome (total 47 chromosomes), and this
abnormality is denoted as "47,XYY". Such individuals are often
characterized by tallness, severe acne, and sometimes skeletal
malformations and mental deficiency. It has been suggested that
the presence of an extra Y chromosome in an individual may cause
him to be more aggressive and prone to criminal behavior, but
recent studies of the general population have cast doubt on the
validity of this linkage.
... ... *limbic system: In general, this refers to those cortical
and subcortical structures ("cortical" refers to cerebral cortex)
concerned with the emotions. The most prominent anatomical
components of the limbic system are the cingulate gyrus, the
hippocampus, and the amygdala, all "deep brain" structures and
not visible on the exterior surface of the brain.
... ... *frontal lobes: One of the four lobes of the brain. The
other lobes are the parietal lobe, the temporal lobe, and the
occipital lobe. Each hemisphere has these 4 lobes.
... ... *amygdala: A cellular complex in the temporal lobe that
forms part of the limbic system. The major functional correlates
of the amygdala are autonomic nervous system behavior, emotional
behavior, and sexual behavior.
... ... *orbitofrontal cortices: The orbitofrontal cortex lies
directly under the forehead skull.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 13Apr01
For more information: http://scienceweek.com/swfr.htm
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7. IN FOCUS: ON SCIENCE AND CREATIVITY
"What a scientist does is compounded of two interests: the
interest of his time and his own interest. In this he behaves as
does any other man. The need of the age gives its shape to
scientific progress as a whole. But it is not the need of the age
which gives the individual scientist his sense of pleasure and of
adventure, and that excitement which keeps him working late into
the night when all the useful typists have gone home at five
o'clock. He is personally involved in his work, as the poet is in
his, and as the artist is in the painting. Paints and painting
too must have been made for useful ends; and language was
developed, from whatever beginnings, for practical communication.
Yet you cannot have a man handle paints or language or the
symbolic concepts of physics, you cannot even have him stain a
microscope slide, without instantly waking in him a pleasure in
the very language, a sense of exploring his own activity. This
sense lies at the heart of creation. The sense of personal
exploration is as urgent, and as delightful, to the practical
scientist as to the theoretical. Those who think otherwise are
confusing what is practical with what is humdrum. Good humdrum
work without originality is done every day by every one,
theoretical scientists as well as practical, and writers and
painters too, as well as truck drivers and bank clerks. Of course
the original work keeps the world going; but it is not therefore
the monopoly of practical men. And neither need the practical man
be unoriginal. If he is to break out of what has been done
before, he must bring to his own tools the same sense of pride
and discovery which the poet brings to words. He cannot afford to
be less radical in conceiving and less creative in designing a
new turbine than a new world system."
-----------
J. Bronowski: "Science and Human Values"
(The Nation 1956 183:550)
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8. FROM THE SCIENCEWEEK ARCHIVE
COGNITIVE SCIENCE: NUMBERS AND COUNTING IN A CHIMPANZEE
In this context, let us define "animals" as all living multi-
cellular creatures other than humans that are not plants. In
recent decades it has become apparent that the cognitive skills
of many animals, especially non-human primates, are greater than
previously suspected. Part of the problem in research on
cognition in animals has been the intrinsic difficulty in
communicating with or testing animals, a difficulty that makes
the outcome of a cognitive experiment heavily dependent on the
ingenuity of the experimental approach. Another problem is that
when investigating the non-human primates, the animals whose
cognitive skills are closest to that of humans, one cannot do
experiments on large populations because such populations either
do not exist or are prohibitively expensive to maintain. The
result is that in the area of primate cognitive research reported
experiments are often "anecdotal", i.e., experiments involving
only a few or even a single animal subject. But anecdotal
evidence can often be of great significance and have startling
implications: a report, even in a single animal, of important
abstract abilities, numeric or conceptual, is worthy of
attention, if only because it may destroy old myths and point to
new directions in methodology. In 1985, T. Matsuzawa reported
experiments with a female chimpanzee that had learned to use
Arabic numerals to represent numbers of items. This animal (which
is still alive and whose name is "Ai") can count from 0 to 9
items, which she demonstrates by touching the appropriate number
on a touch-sensitive monitor. Ai can also order the numbers from
0 to 9 in sequence.
... ... N. Kawai and T. Matsuzawa (Primate Research Institute
Kyoto, JP) now report an investigation of Ai's memory span by
testing her skill in numerical tasks, the authors making the
following points:
1) The authors point out that humans can easily memorize
strings of codes such as phone numbers and postal codes if they
consist of up to 7 items, but above this number of items, humans
find memorization more difficult. This "magic number 7" effect,
as it is known in human information processing, represents an
apparent limit for the number of items that can be handled
simultaneously by the human brain.
2) The authors report that the chimpanzee Ai can remember
the correct sequence of any 5 numbers selected from the range 0
to 9.
3) The authors relate that in one testing session, after
choosing the first correct number in a sequence (all other
numbers still masked), "a fight broke out among a group of
chimpanzees outside the room, accompanied by loud screaming. Ai
abandoned her task and paid attention to the fight for about 20
seconds, after which she returned to the screen and completed the
trial without error."
4) The authors conclude: "Ai's performance shows that
chimpanzees can remember the sequence of at least 5 numbers, the
same as (or even more than) preschool children. Our study and
others demonstrate the rudimentary form of numerical competence
in non-human primates."
-----------
N. Kawai and T. Matsuzawa: Numerical memory span in a chimpanzee.
(NAT 2000 403:39)
QY: Tetsuro Matzuzawa [matsuzaw@pri.kyoto-u.ac.jp]
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 21Apr00
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9. SOURCES:
AGP: Archives of General Psychiatry
APL: Applied Physics Letters
AS: American Scientist
CEN: Chemical & Engineering News
GD: Genes & Development
GR: Genome Research
ICAR: Icarus
JAMA: Journal of the American Medical Association
JCE: Journal of Chemical Education
NAT: Nature
NEJM: New England Journal of Medicine
NYT: New York Times
PNAS: Proceedings of the National Academy of Sciences
PRL: Physical Review Letters
PT: Physics Today
SA: Scientific American
SCI: Science
SK: Skeptic
SW: ScienceWeek
TB: The Biochemist
TS: The Scientist
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