ScienceWeek

SCIENCE-WEEK

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A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy makers.

May 14, 1999 -- Vol. 3 Number 20

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And the end of all our exploring
Will be to arrive where we started
And know the place for the first time.
-- T.S. Eliot (1888-1965)

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Contents of This Issue:

1. On Access to Essential Drugs in Poor Countries
2. On Barred Galaxies
3. On Thermoelectric Devices
4. A Specific Glial-Neuronal Signaling Pathway
5. On the Timing of Human Birth
6. Leukotrienes and the Treatment of Asthma

In Focus: On Sociobiology

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1. ON ACCESS TO ESSENTIAL DRUGS IN POOR COUNTRIES
In the last issue of this publication (SW 7 May 99 3:19), we
briefed a report on the current situation concerning the
availability of anti-AIDS drugs in developing countries. A
similar situation exists for a number of other serious epidemic
diseases, in particular for a complex of tropical and other
diseases common in Africa. For more than a century, researchers
in chemistry, biology, and medical science have joined together
in an intensive research effort to combat the deadly diseases
that have ravaged the human species. But it seems that at present
only a small part of the world population, the richer part, is
experiencing the benefits of this effort.
... ... B. Pecoul et al (4 authors at Medicine Without Frontiers
Foundation, FR) present an extensive analysis of the current
problems concerning access to essential drugs in developing
countries, the authors making the following points: 1) At the
present time, entire populations lack access to essential quality
drugs, and the situation appears to be deteriorating. The result
is a further marginalization of much of the world's population.
2) Effective treatment is lacking in poor countries for many
diseases, including *African trypanosomiasis, *Shigella
dysentery, *leishmaniasis, tuberculosis, and *bacterial
meningitis. Treatment may be precluded because no effective drug
exists, the drug is too expensive, or the drug has been withdrawn
from the market. Moreover, research and development in tropical
diseases have come to a near standstill. 3) A serious problem
concerns the local standards for drug production, since many of
the poorer countries do not have the technical, financial, or
human resources required for the application of necessary
standards, and some developed countries may be less strict when
the product being manufactured is designed for export. The
quality of drugs and their effectiveness and safety are less
certain in populations of the poorest people, who are attracted
by lower-priced drugs sold outside pharmacies. Also, both large-
scale and small scale counterfeiting of drugs is a serious
problem. In 1995, for example, during a meningitis epidemic in
Niger that caused 41,000 reported cases of the disease, an
estimated 60,000 persons were inoculated with totally inactive
counterfeit vaccines apparently substituted for the original
vaccines donated by Pasteur Merieux, SmithKline Beecham, and the
neighboring Nigerian government. 3) Drugs necessary for the
treatment of certain tropical diseases have begun to disappear
from the market because they are commercially unprofitable. Many
of these drugs were discovered in the 1950s and 1960s or earlier
and are currently seldom or never used in wealthy countries,
which means a profitable market has ceased to exist. 4) The
prohibitive cost of *antiretroviral drugs for treatment of AIDS
is well known, but there are many other examples of drugs that
are simply not affordable, most of which have been recently
marketed and are still patent-protected. 5) Tuberculosis caused
the deaths of 3 million people in 1997, but the current treatment
regimen is impractical in poor countries and compliance is poor.
At present, people with *multi-drug-resistant tuberculosis in
countries with limited financial resources are not receiving
treatment, "which from a medical and humanitarian perspective is
completely unacceptable." 6) Directors of pharmaceutical
companies in the developed world have stated repeatedly that the
reason for not conducting research on tropical diseases is the
lack of patent protection for innovations in some in some of the
poor countries, which would also explain the limited investments
of the pharmaceutical companies in the countries concerned.
However, with or without patent protection, it is unlikely that
Western manufacturers will devote much of their effort to
financially nonsolvent populations. All things considered, even
if patents are widely enforced, the future of tropical disease
research may not be promising. 7) The authors conclude: "Access
to essential drugs is a basic human right often denied to people
in poor countries. However, it would serve no purpose to demand
new public health or human rights in a manner that would suggest
that such rights will soon become a reality. The current
situation points to the opposite. For a great proportion of the
world, health conditions are worsening, and without fundamental
change in the pharmaceutical market, perspectives [prospects] for
improvement are not encouraging."
-----------
B. Pecoul et al: Access to essential drugs in poor countries.
(J. Amer. Med. Assoc. 27 Jan 99 281:361)
QY: Bernard Pecoul [office@paris.mcf.org]
-----------
Text Notes:
... ... *African trypanosomiasis: (sleeping sickness) Transmitted
by tsetse flies (Glossina). There are two varieties of the
African parasite: Trypanosoma brucei rhodesiense and Trypanosoma
brucei gambiense. American trypanosomiasis is transmitted by
"cone-nosed bugs" (Triatoma, etc.). the American parasite,
labelled Trypanosoma (Schizotrypanum) cruzi, causes Chagas'
disease. Trypanosomes are motile protozoans residing in blood
(hemoflagellates).
... ... *Shigella dysentery: Shigella is a genus of nonmotile
bacteria. The species S. dysenteriae (Shiga bacillus) causes
dysentery in humans and in monkeys.
... ... *leishmaniasis: Infection with Leishmania, a genus of
motile protozoa related to the trypanosomes. Leishmaniasis is a
clinically ill-defined group of diseases, usually divided into 4
types, one of which is kala-azar. Each disease is transmitted by
a sandfly species.
... ... *bacterial meningitis: In general, meningitis is any
inflammation of the membranes (meninges) of the brain or spinal
cord.
... ... *antiretroviral drugs: An "antiretroviral drug" is any
drug acting against retroviruses. Retroviruses are single-
stranded RNA viruses that have an enzyme called reverse
transcriptase, and with this enzyme the viral RNA is used as a
template to produce viral DNA from cellular material. This DNA is
then incorporated into the host cell's genome, where it codes for
the synthesis of viral components. The HIV virus is a retrovirus.
... ... *multi-drug-resistant tuberculosis: Tuberculosis is a
specific disease caused by Mycobacterium tuberculosis, which may
affect almost any tissue or organ of the body, but most commonly
the lungs. A number of drug-resistant strains of M. tuberculosis
have evolved, including some strains that are resistant to all or
nearly all the drugs known to be active against the pathogen.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99


2. ON BARRED GALAXIES
In general, a "galaxy" is a system of stars, often with
interstellar gas and dust, the components bound together by
gravity. Galaxies are the principal visible structures in the
Universe, varying in size from "dwarfs" with less than 1 million
stars to supergiants with more than 10^(12) stars. In diameter,
galaxies range from a few hundred light years to over 600,000
light years. In general, galaxies are of 3 morphological types:
elliptical, spiral, and irregular. Of the spiral galaxies, there
are in turn 3 subtypes: S0 (spiral-subtype 0) galaxies, normal
spirals, and barred spirals. An S0 galaxy shows no obvious spiral
arms, but there is an obvious disk component with a large nuclear
bulge at the center. The so-called "barred spiral galaxy" is a
type of disk galaxy with spiral arms extending from an almost
rectangular or cigar-shaped bar of stars across its central
regions, and this bar can account for up to one-third of the
galaxy's total light output. There exists an alternative
classification scheme (the so-called "Hubble classification"
proposed by Edwin Hubble in the 1920s) which has 4 main types of
galaxies: ellipticals, spirals, barred spirals, and irregulars,
but at this stage in our meager knowledge of the evolution and
structure of galaxies, any classification scheme is rather
arbitrary. The important fact is that galaxies have differing
morphologies. In barred spiral galaxies, the central bars are
typically between 2.5 to 5 times as long as they are wide. Almost
half of all disk galaxies contain a noticeable bar, and it is
thought that similar but much less prominent structures may exist
in most disk galaxies. It is not yet clear whether bars are a
permanent or transient galactic structure. ... ... P. Martin and
D. Friedli (2 installations, CA CH) present a review of current
work concerning barred spiral galaxies, the authors making the
following points: 1) Before the development of electronic
detectors with large dynamic ranges, the bright inner parts of
galaxies remained unknown because they typically saturated
photographic plates. Upon their arrival in the 1970s and 1980s,
CCDs (*charge-coupled devices) and infrared arrays made possible
the study of these regions of galaxies. It immediately became
apparent that the bars of barred spiral galaxies were more
complicated than expected. For example, some galaxies that appear
unbarred in visible light exhibit a bar at infrared wavelengths.
2) Other key information derives from spectroscopic measurements
of *Doppler shifts in galaxy bars. Precise measurements of
rotation velocity at different locations have revealed that bars
rotate as solid bodies at a specific frequency ("pattern speed").
In other words, all the points along a bar take the same time to
turn once around the center of the galaxy. This contrasts with
the differential rotation observed in the disks of unbarred
galaxies. 3) Radio telescope observations have been particularly
useful for studying gas kinematics along bars, and strong
noncircular *shearing motions have been identified. At 100
kilometers per second or more, these motions greatly exceed the
apparent speeds at which gas clouds move in the disk of an
unbarred galaxy (typically 30 kilometers per second). These
observations strongly support the idea that gas clouds are
funneled along bars and perhaps are triggering central
*starbursts and fueling *active galactic nuclei. 4) Barred
galaxies are not rare as was once thought. Among spiral galaxies,
more than two-thirds have a bar (including our own Milky Way).
Near-infrared spectroscopic observations continue to reveal
previously unsuspected bars, and the observed barred-to-unbarred
ratio is likely to increase as new data become available. 5)
Astronomers have long thought that the morphological
characteristics of galaxies were determined at the birth of the
galaxy and then preserved forever. However, during the past 15
years, this view has profoundly changed, and galaxies are no
longer seen as immutable objects: galaxies apparently evolve,
interact, and merge. The relationship between the structure and
history of a galaxy is an important problem yet to be solved.
-----------
P. Martin and D. Friedli: At the hearts of barred galaxies.
(Sky & Telescope March 1999)
QY: Pierre Martin, Canada-France-Hawaii Telescope, Hawaii US.
-----------
Text Notes:
... ... *charge-coupled devices: In general, a charge-coupled
device is a silicon chip containing an array of light-sensitive
diodes, the array used to capture images. The photodiodes become
charged when light falls upon them, the amount of charge
depending on the amount of light. These devices are widely used
in astronomy, as they are more sensitive to light than a
photographic emulsion.
... ... *Doppler shifts: (Doppler effects) A Doppler shift is the
change of wavelength of electromagnetic radiation as a result of
relative movement between source and observer.
... ... *shearing motions: In general, a shearing force is a
force that acts parallel to a plane rather than perpendicular to
the plane. In this context, shearing motions are motions parallel
to the plane of the galactic disk.
... ... *starbursts: In general, a starburst is a massive burst
of localized star formation in a galaxy.
... ... *active galactic nuclei: The "nucleus" in this context is
the central region of a galaxy, a region that often has a complex
structure involving a dense cluster of stars. The nucleus can be
the site of considerable activity, and if the radiation emitted
is high enough, it is classed as an "active galactic nucleus".
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99
-------------------
Related Background:
STAR FORMATION AND GALAXY COLLISIONS
Galaxies, systems of stars, interstellar gas, and interstellar
dust all bound together by gravity, range from dwarf galaxies of
a million stars to supergiant galaxies with over 10^(12) stars.
During this century, our views concerning galaxies other than our
own have undergone considerable revision. ... ... R. Genzel et al
present a review of recent work on galaxy collisions, and the
authors make the following points: 1) Not until 1920 was it
established that "galaxies" are large concentrations of stars and
interstellar gas like our Milky Way, but located large distances
away. Until the mid 1950s, the accepted view was that galaxies
are "island universes" very much isolated from each other. 2) In
1956, The astronomer Fritz Zwicky called attention to filaments
and jets of stars in adjacent galaxies, and he suggested these
could be large scale "tidal effects" due to the galactic mutual
gravitational interaction. But Zwicky's interpretation met with
widespread skepticism until numerical models indicated the slow
but close passage of two galaxies can create long tails, bridges,
and spiral structures purely as the result of the gravitational
forces and torques between the two colliding galaxies. 3) The
consensus view of galaxies changed after the mid-1980s as a
result of the first space-borne *infrared telescope (IRAS), which
surveyed the entire sky in the 12 to 120 micron band. Although
most of the several tens of thousands of galaxies identified by
IRAS are normal galaxies like our own Milky Way, there are also
now hundreds of identified galaxies whose total energy output is
dominated by emission in the far infrared band, and the most
spectacular of these are the ultra-luminous infrared galaxies,
which have luminosities resembling that of extreme *active
galactic nuclei such as *quasars. Recent observations have
established that most of these ultra-luminous infrared galaxies
are extreme interacting systems with strong signatures of recent
tidal disturbances, in some cases showing that the two galaxies
are actually close to merging into a single system. The key
questions are, a) Why is there such a strong correlation between
infrared luminosity and galaxy interaction? b) What powers these
galaxies (active star formation or *black holes)?, and c) How are
these galaxies evolving with time? The authors summarize: "It is
becoming increasingly clear that collisions between galaxies play
an important role in galaxy evolution. The ultraluminous infrared
galaxies are predominantly powered by enormous star-formation
events that are triggered in the last phases of such collisions.
These bursts occur just before the galaxies merge to form single
*elliptical galaxies."
-----------
R. Genzel et al (Max Planck Institute for Extraterrestrial
Physics Garching, DE)
Star formation triggered by galaxy collisions.
(Nature 29 Oct 98 395:859)
QY: Reinhard Genzel, Max-Planck Institut fur Extraterrestrische
Physik, 85740 Garching, DE.
-----------
Text Notes:
... ... *infrared telescope: Infrared radiation involves
wavelengths between the red end of the visible spectrum and the
radio bands of the spectrum, from about 0.8 microns to about 1000
microns. The submillimeter infrared band lies between the
far-infrared band (at about 0.1 millimeter) and the microwave
band (above 1 millimeter). Submillimeter wavelengths trace
directly the emission from dust that has been warmed by massive
star-formation activity.
... ... *active galactic nuclei: Central regions of galaxies in
which considerable energy is generated by processes other than
those operating in ordinary stars. The energy may result from the
accretion of material into a massive black hole situated at the
core of the galaxy.
... ... *quasars: (quasi-stellar objects). Extremely luminous
sources radiating energy over the entire spectrum from x-rays to
radio waves, and which are apparently the oldest and most distant
objects in the universe. They are believed to involve massive
*black holes
... ... *black holes: If the terminal stages of star death leave
a remnant star mass greater than 3 solar masses, the ultimate
gravitational collapse will produce a "black hole", a
relativistic singularity. A black hole is a localized region of
space from which neither matter nor radiation can escape. The
"trapping" occurs because the requisite escape velocity, which
can be calculated from the relevant equations, exceeds the
velocity of light and is therefore unattainable. Another view of
a black hole is that it is a mass that has collapsed to such a
small volume that its gravity prevents the escape of all
radiation. If quasars indeed involve black holes, the radiation
is from material just outside the black hole, and not from
anything within it. Nothing inside a black hole can get out of
it.
... ... *elliptical galaxies: In 1925, the astronomer Edwin
Hubble introduced a classification scheme for galaxies that is
now widely used. The scheme has 3 main types of galaxy:
elliptical, spiral, and barred spiral, and each is further
divided into morphological subtypes. Elliptical galaxies are
apparently composed of old stars, contain little dust, are the
central dominant galaxies in rich clusters, and many are powerful
sources of radio wavelength radiation. The size of elliptic
galaxies ranges from dwarf ellipticals (10^(8) stars) to
supergiant ellipticals (10^(13) stars). Elliptical galaxies are
believed to be a stage in the evolution of galaxies, and
different cosmological models make specific predictions about the
number of elliptical galaxies as a function of redshift. In
principle, therefore, observations of elliptical galaxies can be
used to discriminate between models.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 20Nov98
-------------------
Related Background:
ON THE EVOLUTION OF GALAXIES IN A CHANGING UNIVERSE
In a detailed review of research in this century concerning the
evolution of galaxies, Alan Dressler (Carnegie Observatories
Pasadena, US) makes the following points: 1) When the century
opened, most astronomers assumed the Universe was eternal and
basically changeless, its general structure immutable. In 1915,
with the publication of Einstein's general theory of relativity,
there were implications of the cosmic role of gravity, but these
implications were for the most part ignored. Indeed, even after
1924 and the proof by *Edwin Hubble (1889-1953) that the spiral
nebulae are other galaxies at vast distances, astronomers were
slow to recognize the implications of the new observations. 2)
The first big step in changing the view of the cosmos was the
construction by *George Ellery Hale (1868-1938) of the 100-inch
Hooker reflector on Mount Wilson (US), a project completed in
1918. This was the telescope used by Hubble and his colleagues to
reveal the large-scale organization of the Universe into
galaxies, the vast size of the Universe, and the expansion of the
Universe. *George Lemaitre (1894-1966) soon proposed that the
expansion of the Universe implied a dense explosive birth of the
Universe at a specific finite time in the past (the event that
came to be called the Big Bang). 3) An even greater telescope was
needed, and again George Hale led the way in the building of the
200-inch reflector on Palomar Mountain (US), that instrument
finally completed in 1948. The 200-inch telescope produced the
first observations of galaxy evolution -- the first evidence that
galaxies observed at high *redshift are unlike galaxies closer to
us in time. An even greater accomplishment of the 200-inch
telescope was a series of observations concerning the spectra of
*quasars, and the evidence for their immense distances and
luminosities. Theorists eventually proposed that quasars were
*black holes of 100 million solar-masses or more. It is now clear
that most galaxies with a central bulge, including our own
Galaxy, harbor massive black holes at their cores. 4) In 1961,
Allan Sandage published a landmark paper outlining the
possibility of testing cosmological models with the 200-inch
telescope, and over the next two decades Sandage devoted himself
to this project. Unfortunately, the underlying premise of the
project -- that the brightest galaxy in every galactic cluster
has about the same true luminosity -- was demonstrated by
*Beatrice Tinsley (1941-1981) to be untenable. 5) In the fall of
1977, at a Yale University (US) conference on the evolution of
galaxies, Harvey Butcher and Augustus Oemler presented their
evidence for relatively young star-forming galaxies. This
evidence, which implied strong galaxy evolution during relatively
recent cosmic time, met with controversy and skepticism. 6) In
the 1980s, observations by various groups proved that Butcher and
Oemler were correct, and it was now understood that these
relatively young galaxies were often producing new stars in huge
bursts. These bursting galaxies are evidently spirals with a more
disheveled appearance than is common today, and in their twisted
and distorted disks huge numbers of stars were recently born. 7)
During the past 2 years, among the most interesting results of
various observations with various instruments is the formulation
of the so-called Madau diagram (popularized by Piero Madau) that
plots the Universe-wide rate of star formation from early times
to today, spanning almost the whole history of the cosmos. The
rate of star formation apparently rose rapidly in the first few
billion years, the peak rate at about 5 or 6 billion years later
at redshifts of 1 to 2. (Our Sun apparently formed at a time
corresponding approximately to redshift = 0.5.) The author
concludes: "Our generations are fortunate to live to see one of
the great mysteries of where we came from in process of being
solved."
QY: Alan Dressler, Carnegie Observatories, Pasadena, Ca. US.
(Sky & Telescope October 1998) (Science-Week 11 Sep 98)
-------------------
Related Background:
... ... *Edwin Hubble (1889-1953): Hubble first studied law
before switching to astronomy at the age of 25. He began his work
at the Mount Wilson Observatory with the 100-inch telescope at
the age of 30. In 1941, at the age of 52, he tried to join the US
Army to fight the Nazis, but he was persuaded that he could do
more in war-related research. 
... ... *George Ellery Hale (1868-1938): Hale is best known for
his work building large-telescopes (and for obtaining the funds
for the Yerkes Observatory, named after the street-car magnate
Charles Tyson Yerkes), but already at the age of 21 he invented
the spectroheliograph, a device that made it possible to
photograph the light of a single spectral line of the sun, and he
made several ground-breaking observations with this instrument.
... ... *George Lemaitre (1894-1966): Lemaitre began his
professional life as a civil engineer, then at 21 he switched to
physics and mathematics. He also became a Roman Catholic priest
at the age of 22. After obtaining his PhD at the Massachusetts
Institute of Technology in 1927, he settled in Belgium as a
professor of astrophysics at the University of Louvain. At the
time of his death, he was president of the Pontifical Academy of
Sciences at Rome. Lemaitre's theoretical ideas concerning the
origin of the Universe were published in 1927, when he was 31,
but the paper was largely unnoticed until the astrophysicist
Arthur Eddington (1882-1944) called attention to it much later.
... ... *redshift: Redshift (symbol: z) is a lengthening of the
wavelengths of electromagnetic radiation from a source caused
either by the movement of the source (Doppler effect) or by the
expansion of the universe (cosmological redshift). Redshift is
defined as the change in wavelength of a particular spectral line
divided by the unshifted wavelength of that line. Large redshifts
imply large radial velocities (which imply large distances,
according to current cosmological theory), but at redshifts
greater than about 0.2 there is a relativistic divergence from a
linear relation. A redshift of 4.0 corresponds to an object
receding with a radial velocity 92% that of the velocity of
light. The largest astrophysical redshifts so far observed are of
the order of z = 4.9.
... ... *quasars: (quasi-stellar objects). Extremely luminous
sources radiating energy over the entire spectrum from x-rays to
radio waves, and which are apparently the oldest and most distant
objects in the universe.
... ... *black holes: If the terminal stages of star death leave
a remnant star mass greater than 3 solar-masses, the ultimate
gravitational collapse will produce a black hole, a relativistic
singularity. A black hole is a localized region of space from
which neither matter nor radiation can escape. The "trapping"
occurs because the requisite escape velocity, which can be
calculated from the relevant equations, exceeds the velocity of
light and is therefore unattainable. Another view of a black hole
is that it is a mass that has collapsed to such a small volume
that its gravity prevents the escape of all radiation. Space and
time essentially have no meaning in a black hole. The boundary of
the black hole is called the "event horizon", because any event
within the boundary is invisible outside, the invisibility
resulting from the fact that no radiation can escape to be
detected. The radius of the black hole depends upon how much
matter has fallen into the region; it is called the "Schwarzchild
radius", and it is usually a few kilometers. However, massive
black holes are possible and are thought to be the source of
quasars. If quasars indeed involve black holes, the radiation is
from material just outside the black hole, and not from anything
within it. Nothing inside a black hole can get out of it.
... ... *Beatrice Tinsley (1941-1981): During her short life,
Tinsley managed to be a force in astronomy from her first entry
into the field. At the age of 25, an unknown graduate student at
the University of Texas, she rose before an audience about to
hear Allan Sandage and publicly challenged his idea that giant
elliptical galaxies exhibited luminosities constant enough to be
used as "standard candles" to estimate distances. She proved her
point by the age of 36, and the variability of galaxy
luminosities became the consensus view. It was Tinsley who co-
hosted the 1977 Yale conference that set the course of galaxy-
evolution studies. She died 4 years later of cancer. Near the
end, she wrote the following: "Let me be like Bach, creating
fugues; till suddenly the pen will move no more."
-------------------
Related Background:
ON THE FORMATION OF ELLIPTICAL GALAXIES
... The furthest galaxy on record is at a redshift z = 4.92),
which implies a distance of approximately 13 billion light years
(i.e., an object date of 13 billion years ago.) The term "near
infrared" refers to the range 0.8 to 8 microns. Now S. Zepf
(Univ. of California Berkeley, US) reports an analysis of deep
optical and near-infrared images indicates there are fewer
galaxies with very red colors than predicted by models that
propose completion of elliptical galaxy star formation by
approximately z = 5. This suggests that elliptical galaxies must
have significant star formation at z [ 5. The author proposes
that either ellipticals form at moderate redshifts, where a large
initial burst of star formation is shrouded by dust, or that they
form through the merging of smaller galaxies.
QY: Stephen A. Zepf [zepf@astro.yale.edu]
(Nature 27 Nov 97) (Science-Week 19 Dec 97)
-------------------
Related Background:
ASTRONOMERS AGREEING ON THEORY OF GALAXY FORMATION AND EVOLUTION
Among contemporary cosmologists, there are two prevailing models
for the formation of galaxies. One model is hierarchical, in the
sense that small amorphous proto-galaxies are considered to form
first, these evolving into spiral galaxies, and the spiral
galaxies then merging to form elliptical galaxies. The other
model is a completely different picture, considering the various
galaxies to form from the condensation of single massive dust
clouds, with the particular type of galaxy formed dependent on
the nature of the dust cloud collapse. At two recent cosmology
symposia, in view of new red-shift data (shifts to the red end of
the spectrum of light from the galaxies) provided by the Hubble
Space Telescope, cosmologists are apparently forming a consensus
that the first idea, the hierarchical model, is more consistent
with the observed data than the second model. The Hubble Space
Telescope has brought a renaissance to cosmology, and we are only
at the beginning of the new era.
(Nature 26 Jun 97) (Science-Week 3 Jul 97)


3. ON THERMOELECTRIC DEVICES
In nature, what are called "thermoelectric" effects occur when
both electric and thermal currents are present. (So-called
"transverse thermoelectric effects" occur when in addition there
is a magnetic field normal to these currents.) There are
essentially three ordinary thermoelectric effects. The "Seebeck
effect" (discovered in 1822) relates to the electromotive force
developed in a circuit consisting of different conducting
elements, not all of whose contacts are at the same temperature.
The "Peltier effect" (discovered in 1834) involves the reversible
heating or cooling which occurs at a contact between two
dissimilar conductors when electric current flows from one
conductor to another. The "Thomson effect" (discovered by Lord
Kelvin in 1856) refers to the reversible heat absorption which
occurs when an electric current flows in a homogeneous conductor
in which there is a temperature gradient. All three effects are
related by thermodynamics: if one effect is known, the other two
can be derived. ... ... Terry M. Tritt (Clemson University, US)
presents a short review of current advances in the application of
the Peltier effect to achieve cooling of materials, the author
making the following points: 1) The cooling of electronic devices
is often necessary to optimize performance. Traditional
approaches to cooling are usually based on thermodynamic cycles
involving compression and expansion of refrigerant gases (e.g.,
Freon). Thermoelectric materials, in contrast, do not rely on
chemicals or gases but rather on the Peltier effect in solids.
This has distinct advantages in that it is solid-state
refrigeration, without moving parts and vibrations, and with
quiet performance and the ability for localized "spot" cooling.
These aspects can be of considerable importance for many
semiconducting and other electronic devices. 2) In the past, the
application of thermoelectric devices has been frustrated by the
low efficiency of these devices, and the applications have
remained limited. Recently, however, new thermoelectric materials
for practical refrigeration applications have been developed. 3)
In general, the key to a useful thermoelectric material depends
on the achievement of good electrical conductivity and poor
thermal conductivity [*Note #1]. This is related to a concept
formulated by G.A. Slack in the 1970s: a good thermoelectric
material should be based on a *phonon-glass/electron-crystal
model. In other words, the material should have the electronic
properties of a crystalline material and the thermal properties
of glass. 4) Slack's concept, when applied to semiconductors,
centers around minimizing the lattice thermal conductivity of a
material by inserting loosely bound atoms (called "rattlers")
into the voids or holes in the structure. These rattlers will
move or bounce around inside these voids and thus scatter phonons
(quantized lattice vibrations), the result an effective reduction
and possible minimization of lattice thermal conductivity. 5) A
variety of approaches to the development of useful thermoelectric
materials are now being followed in various laboratories, and
many of the different approaches -- thin films and bulk
materials, varieties of semiconductor materials, etc. -- are
apparently showing promise. 6) The author concludes: "The
development of the next generation of thermoelectric materials,
especially for thermoelectric cooling well below room
temperature, could tremendously alter a number of high-tech
industries. Although a clear frontrunner cannot yet be
identified, the diversity of approaches suggest that we may not
need to wait another 30 years for the next generation of
thermoelectric materials."
-----------
Terry M. Tritt: Holey and unholey semiconductors.
(Science 5 Feb 99 283:804)
QY: Terry M. Tritt [ttritt@clemson.edu]
-----------
Text Notes:
... ... *Note #1: In thermoelectric materials, heat is not
primarily transported by the lattice but by the electrical charge
carriers. Applying an electric current through a thermoelectric
material thus cools one end and transports the heat to the other
end of the material or device, with an efficiency that depends on
the heat conduction properties of the lattice through which the
heat carriers are moving. If heat conduction in the lattice is
poor, the temperature gradient produced by the electrical charge
carriers can be maintained. Thus, the ideal thermoelectric
material is at the same time both a poor heat conductor and a
good electrical conductor.
... ... *phonon: Phonons are virtual particles associated with
crystal thermal vibrations.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99


4. A SPECIFIC GLIAL-NEURONAL SIGNALING PATHWAY
In the 19th century, biologists recognized that cells in the
brain could be divided into two distinct types: a) neurons, and
b) a far more numerous group of cells that appear to surround the
neurons and fill spaces between them. This second category of
cells was called "neuroglia", literally "nerve glue", the
implication being that one of the functions of these cells is to
hold the neurons in place. Although there is little evidence for
this gluing function, and the idea has essentially been
abandoned, the name "neuroglia" (or glia) has remained in use.
Glial cells have been implicated or shown to be directly involved
in a number of important neurobiological processes and pathways,
but in general, neurobiologists have relegated glia to a role
secondary to that of neurons because it has been thought that
neurons are the only cells capable of intracellular and
intercellular signaling. Recently, however, there has been
evidence accumulating that glia may in fact be active
participants in brain signaling, and there is some indication
that glia actively determine neuronal function by secreting
unknown factors that affect neuronal membrane excitability.
... ... L-L. Yuan and B. Ganetzky (University of Wisconsin
Madison, US) now report that in the fruit fly Drosophila a
specific gene (axotactin) encodes a member of the *neurexin
protein superfamily, the protein secreted by glia and
subsequently localized to *axonal tracts. Null mutation (i.e.,
elimination of the gene by mutation) caused temperature sensitive
paralysis and a corresponding blockade of axonal conduction. The
authors suggest that the protein expressed by this gene (the
protein denoted as AXO) appears to be a component of a glial-
neuronal signaling mechanism that helps to determine the membrane
electrical properties of target axons. 
-----------
L-L. Yuan and B. Ganetzky: A glial-neuronal signaling pathway
revealed by mutations in a neurexin-related protein.
(Science 26 Feb 99 283:1343)
QY: Barry Ganetzky [ganetzky@facstaff.wisc.edu]
-----------
Text Notes:
... ... *neurexin protein superfamily: Neurexins are a family of
neuronal cell surface proteins with apparent roles in cell
adhesion and intercellular signaling. Three distinct genes
encoding neurexins have been identified in vertebrates. The
neurexins have been grouped with several other proteins into a
"superfamily". In general, in this context, a "superfamily" is
any group of genes and their cognate proteins that can be related
by sequence homology.
... ... *axonal tracts: In general, nerve cells have a single
long extension (the "axon") that propagates the electrical output
(the action potential) of the cell. In some types of nerve cells,
axons are extensively branched into a multitude of fine fibers
that make contact (synapses) with other nerve cells. Axons
transmitting information to distal regions are usually grouped,
and in the central nervous system the groupings are called
"tracts".
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99
-------------------
Related Background:
SECRETION OF GLUTAMATE BY BRAIN ASTROCYTES
Glial cells are more numerous than neurons in the brain, but
their function has been generally characterized as "metabolic" or
"supportive", without much discussion of details, and more is
known about peripheral glial cells than glial cells in the
central nervous system. Astrocytes are the largest glial cells,
with many extensions radiating outward like a starburst, and at
least one of their functions is apparently to maintain the so-
called "blood-brain barrier" effectively separating neural tissue
from blood. ... Kainic acid, an algal neurotoxin, is a structural
analogue of glutamate, and it has been extensively used in
research, since at high concentrations it selectively destroys
glutamate receptor neurons (glutaminergic neurons). Glutamate is
known to act on 3 classes of receptors, one of them called the
kainate receptor because at low concentrations of kainic acid the
action of glutamate on this receptor is enhanced. The chemistry
of this kainate receptor is not yet well-characterized, mainly
because selective ligands for it are not known. Another class of
glutamate receptor is the AMPA receptor [AMPA = (RS)-alpha-amino-
3-hydroxy-5-methyl-4-isoxazoleproprionic acid], and the third is
NMDA (N-methyl-D-aspartate). These 3 receptors are ionotropic,
i.e., their activation produces changes in membrane ion permeab-
ility. According to another and more recent scheme of glutamate
receptor classification, one receptor type is AMPA/kainate
(ionotropic), another receptor type is NMDA (ionotropic), and a
third receptor type is a slow-acting receptor type coupled to G-
proteins and called metabotropic receptors. (The G-proteins are
membrane-bound proteins that act as transducers between messenger
molecules interacting with the cell surface and the intracellular
messenger system). Prostaglandins are fatty acids secreted by
cells that have hormone-like actions in the immediate vicinity,
and one circumstance that produces their release is tissue
injury. ... ... Bezzi et al (8 authors at 2 installations, IT)
report that coactivation of the AMPA/kainate and metabotropic
glutamate receptors on astrocytes stimulates these cells to
release glutamate through a calcium-dependent process mediated by
prostaglandins. The authors suggest their results reveal a new
pathway of regulated transmitter release from astrocytes, and
that interactions between neurons and astrocytes may play a
critical role in synaptic plasticity and neurotoxicity. They also
suggest that the prostaglandin-mediated glutamate release from
astrocytes may be involved in the pathophysiology of various
brain diseases and injuries.
QY: Andrea Volterra [andrea.volterra@unimi.it]
(Nature 15 Jan 98) (Science-Week 30 Jan 98)


5. ON THE TIMING OF HUMAN BIRTH
An important example of the interplay of hormone signaling in
physiology is provided by the controlled timing of human
parturition -- the delivery of the fetus on schedule. In humans,
the time frame for a "normal" delivery is 37 to 42 weeks
following fertilization. Infants delivered at less than 37 full
weeks are considered "premature", and infants delivered after 42
weeks are considered "postmature", with each category associated
with a different set of possible complications. In particular,
premature birth is often associated with breathing difficulties,
*cerebral palsy, intellectual handicaps, and other problems.
Since 6 to 8 percent of all newborns arrive premature, an
understanding of the timing of human parturition is an important
objective. In recent years, the mechanisms controlling the timing
of birth have become more clarified, principally due to an
increased understanding of the biochemistry and physiology of
hormones. It is a classic story of endocrinology, the branch of
physiology devoted to the study of chemical signaling mechanisms.
... ... Roger Smith (University of Newcastle, AU) presents a
review of current research on the timing of birth, the author
making the following points: 1) During most of gestation, the
uterus is essentially a relaxed sac of disconnected *smooth
muscle cells, the sac sealed at its bottom by the tightly closed
ring of the *cervix, which is kept firm and inflexible by tough
*collagen fibers. These structural features are maintained by
progesterone, a steroid hormone secreted by the *placenta from
early in pregnancy into the circulation of the mother. 2) The
placenta, however, also secretes estrogen, a steroid that opposes
progesterone and promotes muscle contractility, and the
progesterone-estrogen balance is a critical parameter. At first,
maternal estrogen levels are relatively low, but they gradually
rise over time. Parturition typically begins when the balance
shifts so that estrogen and other forces favoring contraction
override those blocking it. 3) As maternal estrogen levels rise,
uterine muscle cells (the myometrium) synthesize a protein called
"connexin". This protein forms so-called "gap junctions" between
muscle cells, special junctions that electrically link the muscle
cells to each other so that they can undergo coordinated
contractions [*Note #1]. At the same time, estrogen provokes
muscle cells into displaying large numbers of receptors for the
hormone oxytocin, which is synthesized in the brain and which can
increase the force of uterine contractions and induce labor in a
receptive uterus. 4) As the uterine muscle prepares for labor,
estrogen also promotes the synthesis of a class of "*local
hormones" called "prostaglandins" by placental membranes
overlying the cervix. The prostaglandins induce production in the
cervix of enzymes that digest its collagen fibers, the enzymes
thus converting the cervix into a malleable structure that will
dilate progressively and finally open as the head of the infant
presses against it during labor. 5) While all these changes are
occurring, the hormone cortisol, produced by the fetal adrenal
gland, ensures that the infant's lungs undergo the final changes
required for breathing air: in particular, cortisol at high
levels leads to the production of substances that remove water
from the lungs and enable them to inflate. 6) Current research
indicates that another hormone, "*corticotropin-releasing
hormone", synthesized in humans by both the placenta and the
fetal brain, drives fetal cortisol production and placental
estrogen synthesis, and thus drives parturition. The evidence, in
fact, suggests that maternal blood levels of corticotropin-
releasing hormone measured at 16 to 20 weeks of pregnancy can be
used to roughly predict the term of gestation. Women at 16 to 20
week of pregnancy with high blood levels of corticotropin-
releasing hormone are more likely to subsequently deliver
prematurely, and women with the lowest levels of this hormone are
more likely to subsequently deliver postmature infants. 7) The
author concludes: "The way now seems open for the creation of
tests able to identify pregnant women at high risk of premature
labor and for the development of agents able to modify the
production of corticotropin-releasing hormone or to otherwise
slow the placental clock that controls the timing of delivery."
-----------
Roger Smith: The timing of birth.
(Scientific American March 1999)
QY: Roger Smith, Endocrinology, University of Newcastle, AU.
-----------
Text Notes:
... ... *cerebral palsy: In general, a syndrome related to brain
damage and characterized by defects in motor function,
particularly motor coordination.
... ... *smooth muscle cells: Smooth muscle was originally
differentiated from striated muscle on the basis of microscopic
appearance, but there are important other differences both
functional and molecular, and in general smooth muscle is
specialized for slow sustained contractions such as those
involved in the control of the diameters of blood vessels.
... ... *cervix: the neck of the uterus, connecting the uterus to
the vagina.
... ... *collagen fibers: Collagen is the major structural
protein forming connective tissue components, cartilage, and
bone.
... ... *placenta: The special structure, derived from both the
embryo and the mother, through which exchange of materials
between fetal and maternal circulations occurs.
... ... *Note #1: For a summary of recent research concerning gap
junctions and connexin, see the last issue of SW (7 May 99 3:19)
... ... *local hormones: Hormones that are not stored, but which
are synthesized in response to specific stimuli (see the
following report, #6).
... ... *corticotropin-releasing hormone: (CRH; corticotropin-
releasing factor) Aside from its apparent role in pregnancy, this
hormone, secreted by the mammalian hypothalamus in the brain in
response to neural and chemical stimuli, controls the secretion
of corticotropin (also known as ACTH) by the pituitary gland.
Corticotropin, in turn, stimulates the synthesis and secretion of
various corticosteroid hormones. The prefix "cortico-" derives
from the adrenal cortex (suprarenal cortex), the site of
synthesis and secretion.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99


6. LEUKOTRIENES AND THE TREATMENT OF ASTHMA
Asthma is a disease characterized by reversible lung airway
obstruction, airway inflammation, and increased airway
responsiveness to a variety of stimuli. In the US, approximately
12 million persons have asthma. From 1982 to 1992, the prevalence
of asthma in the US increased by 42 percent, and the death rate
from asthma increased by 40 percent, with the US death rate from
asthma 5 times higher for blacks than for whites. Asthma is the
leading cause of hospitalization for children in the US, and it
is the primary chronic condition causing school absenteeism. In
1990 in the US, hospital care of asthmatics cost in excess of
US$2 billion, and the total cost of asthma care was US$6.21
billion. The airway obstruction in asthma is due to a combination
of factors, including spasm of airway *smooth muscle, *edema of
airway *mucosa, increased mucus secretion, cellular infiltration
of the airway walls (especially by *eosinophils and *leukocytes),
and injury of the airway *epithelium. Recently, a group of drugs
called "leukotriene modifiers" was introduced for the treatment
of asthma, but the role of these drugs in treatment has not yet
been established. In general, a "leukotriene" is a member of a
family of pharmacologically active substances derived from
polyunsaturated fatty acids (especially from *arachidonic acid),
some of which contain a peptide moiety based on cysteine. The
leukotrienes are classified as "local hormones", i.e., hormones
that are not stored, but which are synthesized in response to
specific stimuli. They are formally derived from *eicosanoic acid
and contain a set of 3 conjugated double bonds (thus the suffix
"triene"). The story of the drugs called "leukotriene modifiers"
is a classic example of the interaction of basic science, medical
science, and pharmaceutical industry research and development
leading to the availability of specific drug therapy against an
important human disease. ... ... J.M. Drazen et al (3 authors at
2 installations, US CA) present a review of the use of
leukotrienes in the treatment of asthma, the authors making the
following points: 1) In 1940, Kellaway and Trethewie discovered a
slow-reacting *anaphylaxis-related substance or substances that
stimulated smooth muscle contraction. In 1979, Murphy et al
identified the chemical structures of the chemical entities, the
substances now called the "leukotrienes". The molecules received
the prefix "leuco" because the parent molecule was originally
isolated from leukocytes. The new structural information provided
the key to elaborating the oxidative pathway of lipid metabolism
known as the "*5-lipoxygenase pathway". 2) Respiratory physicians
and scientists had been interested in the classical slow-reacting
substance of anaphylaxis because of the observation that the
substance or substances stimulated airway smooth muscle by a
mechanism that apparently did not involve *histamine. After the
leukotriene structures had been elucidated, the leukotrienes
proved to be potent stimulators of smooth muscle in animal and
human tissues in vitro and in vivo. For example, in normal
subjects, inhalation of one type of leukotriene (D(sub4)) results
in the same degree of airway obstruction as inhalation of
solutions of histamine or *methacholine that are 10,000 times as
concentrated. 3) In addition to their potent *bronchoconstrictor
properties, leukotrienes and other products of the 5-lipoxygenase
pathway induce pathophysiologic responses similar to those
associated with asthma. Specifically, 5-lipoxygenase products can
cause tissue edema and migration of eosinophils, and can
stimulate airway secretions. The leukotrienes also stimulate
*cell cycling and proliferation of both smooth muscle and various
*hematopoietic cells. Since all these responses contribute to
asthma, the pharmaceutical industry initiated research programs
to identify substances that could inhibit the action or synthesis
of the leukotrienes. By early 1998, three chemically distinct
cysteinyl leukotriene-receptor antagonists (Montelukast,
Pranlukast, Zafirlukast) and an inhibitor of leukotriene
synthesis (Zileuton) were available by prescription in more than
a dozen countries. 4) The leukotrienes apparently exert their
biologic actions by binding to and activating specific receptors.
In humans, these receptors are of two types: one type of receptor
mediates constriction of pulmonary vascular smooth muscle, and
the other type of receptor mediates *chemotaxis. Leukotrienes are
apparently produced during asthmatic reactions by cells involved
in the pathogenesis of asthma. The most convincing evidence of a
causative role of leukotrienes in asthma comes from studies of
the effectiveness against asthma of drugs that inhibit the action
or formation of leukotrienes. These so-called "leukotriene
modifiers" are effective in preventing many types of specifically
provoked asthmatic responses. 5) The leukotriene modifiers are
the first new drugs for the treatment of asthma to be introduced
in more than 20 years. Despite their novelty, and the fact that
their exact role remains to be determined, the authors suggest
there are data to support their use in patients with persistent
asthma, whether the asthma is mild, moderate, or severe. 6) The
authors conclude: "Because the leukotriene modifiers are the
first treatment for asthma to result from a search for an
inhibitor of a specific biologic process, these new drugs should
teach us about the pathobiology of asthma while providing orally
available, safe, and effective therapy."
-----------
J.M. Drazen et al: Treatment of asthma with drugs modifying the
leukotriene pathway.
(New England J. Med. 21 Jan 99 340:197)
QY: Jeffrey M. Drazen, Respiratory Disease Division, Brigham and
Women's Hospital, 75 Francis St., Boston, MA 02115 US.
-----------
Text Notes:
... ... *smooth muscle: Smooth muscle was originally
differentiated from striated muscle on the basis of microscopic
appearance, but there are important other differences both
functional and molecular, and in general smooth muscle is
specialized for slow sustained contractions such as those
involved in the control of the diameters of blood vessels.
... ... *edema: In general, an accumulation of an excessive
amount of watery fluid in cells and tissues.
... ... *mucosa: In general, a multilayer tissue lining various
tubular structures in the body.
... ... *eosinophils: A type *leukocyte that stains readily with
eosin dye.
... ... *leukocytes: This is a synonym for "white blood cells",
of which there are many types.
... ... *epithelium: In animals, epithelial cells (epithelium)
compose the cell layers that form the interface between a tissue
and the external environment, for example, the cells of the skin,
the lining of the intestinal tract, and the lung airway passages.
... ... *arachidonic acid: An unsaturated fatty acid, the
biological precursor of a group of hormones (the eiconsanoids),
one subgroup of which is the leukotrienes (the other subgroups
are the prostaglandins and the thromboxanes).
... ... *eicosanoic acid: (arachidic acid) A fatty acid contained
in peanut oil, butter, and other fats.
... ... *anaphylaxis: This term has a number of historical
different meanings. In current usage (and especially in the
context of this report), it refers to an immediate and transient
allergic reaction characterized by contraction of smooth muscle
and dilation of capillaries due to the release of
pharmacologically active substances, including *histamine and the
so-called slow-reacting substances (i.e., the leukotrienes).
... ... *5-lipoxygenase pathway: Lipoxygenase (carotene oxidase,
lipoxidase) is an enzyme that catalyzes the oxidation of
unsaturated fatty acids to yield hydroperoxides of the fatty
acids. 5-lipoxygenase catalyzes the first step in leukotriene
biosynthesis, acting on arichodonate.
... ... *histamine: A local hormone that acts as a powerful
stimulant of gastric secretion, constriction of bronchial smooth
muscle, and dilation of blood vessels.
... ... *methacholine: (Provocholine) A substance with potent
*bronchoconstrictor properties sometimes administered as an
inhalant to test for bronchial hyperreactivity.
... ... *bronchoconstrictor: In general, any agent that causes a
reduction in the caliber of a bronchus or bronchial tube.
... ... *cell cycling: The "cell cycle" is the name given to the
ordered sequence of phases through which a cell passes from one
mitotic cell division to the next.
... ... *hematopoietic cells: (hemopoietic cells) The term
"hematopoiesis" refers to the formation and development of the
various types of blood cells, and "hematopoietic cells" are the
precursor cells of these various types.
... ... *chemotaxis: In general, a movement of cells (or
organisms) in response to chemicals.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
 
IN FOCUS: ON SOCIOBIOLOGY
"Evolutionary theory itself has an appropriately zoocentric
core... But the zoocentric view can be extended too far into a
caricature often called the "nothing but" fallacy (humans are
"nothing but" animals). The simplistic accounts of human
sociobiology now flooding popular literature embody this
overextended version of zoocentrism. Sociobiology is not just any
statement that biology, genetics, and evolutionary theory have
something to do with human behavior. Sociobiology is a specific
theory about the nature of genetic and evolutionary input into
human behavior. It rests upon the view that natural selection is
a virtually omnipotent architect, constructing organisms part by
part as best solutions to problems of life in local environments.
It fragments organisms into "traits", explains their existence as
a set of best solutions, and argues that each trait is a product
of natural selection operating "for" the form or behavior in
question. Applied to humans, it must view _specific_ behaviors
(not just general potentials) as adaptations built by natural
selection and rooted in genetic determinants, for natural
selection is a theory of genetic change. Thus, we are presented
with unproved and unprovable speculations about the adaptive and
genetic basis of specific human behaviors: why some (or all)
people are aggressive, xenophobic, religious, acquisitive, or
homosexual. Zoocentrism is the primary fallacy of human
sociobiology, for this view of human behavior rests on the
argument that if the actions of "lower" animals with simple
nervous systems arise as genetic products of natural selection,
then human behavior should have a similar basis."

-- Stephen Jay Gould: _Hen's Teeth and Horse's Toes_
   (W.W. Norton, New York 1983, p.243)
   [Editor's note: Paleobiologist Stephen Jay Gould is the
current elected President of the American Association for the
Advancement of Science.]


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